Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

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Senthilkumar Sankararaman

2014-01-01

Full Text Available X-linked lymphoproliferative disease (XLP is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV. EBV-induced hemophagocytic lymphohistiocytosis (HLH is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP.

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

Sonke, Gabe S.; Ludwig, Inge; van Oosten, Hannah; Baars, Joke W.; Meijer, Ellen; Kater, Arnon P.; de Jong, Daphne

2008-01-01

Chronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis. These 2 abnormal

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

G.S. Sonke (Gabe); I. Ludwig (Inge); H. van Oosten (Hannah); J.W. Baars (Joke); E. Meijer (Ellen); A.P. Kater (Arnon); D. de Jong (Daphne)

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2

High Level of Perforin Expression Is Required for Effective Correction of Hemophagocytic Lymphohistiocytosis

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Tiwari, Swati; Hontz, Adrianne; Terrell, Catherine E.; Arumugam, Paritha; Carmo, Marlene; Risma, Kimberly; Jordan, Michael; Malik, Punam

2016-01-01

Perforin-1 mutations result in a potentially fatal hemophagocytic lymphohistiocytosis (HLH) with heightened immune activation, hypercytokinemia, pancytopenia, and end-organ damage. At present, hematopoietic stem cell (HSC) transplantation is curative, but limited by donor availability and associated mortality, making gene therapy an attractive alternative approach for HLH. We reported that perforin expression driven by cellular promoters in lentiviral (LV) vectors resulted in significant, alb...

Germline heterozygous variants in genes associated with familial hemophagocytic lymphohistiocytosis as a cause of increased bleeding

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Fager Ferrari, Marcus; Leinoe, Eva; Rossing, Maria

2018-01-01

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by biallelic variants in genes regulating granule secretion in cytotoxic lymphocytes. In FHL3-5, the affected genes UNC13D, STX11 and STXBP2 have further been shown to regulate the secretion of platelet granules, giving rise to compromised...

“Hemophagocytic Lymphohistiocytosis after EBV reactivation and ibrutinib treatment in relapsed/refractory Chronic Lymphocytic Leukemia”

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Maurizio Cavallari

2017-01-01

Full Text Available Hemophagocytic Lymphohistiocytosis (HLH is a rare syndrome characterized by ineffective T-cell and NK response. We report the clinical course of a patient with relapsed CLL who developed acute symptoms soon after starting ibrutinib. Hyperpyrexia, splenomegaly, hyperferritinemia, hypertriglyceridemia, cytopenias, and a typical cytokine pattern, i.e. high interleukin (IL−6, IL10 and IL18, were consistent with a diagnosis of HLH. Coexistent Epstein Barr virus reactivation was documented. Ibrutinib-induced impairment of NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency may have contributed to the development of HLH in our patient.

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

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Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M; Luzzatto, Lucio; Aricò, Maurizio

2016-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. From our registry, we have analyzed a total of 500 unselected patients with HLH. Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Hemophagocytic lymphohistiocytosis preceded by Kikuchi disease in children

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Lim, Gye-Yeon; Cho, Bin; Chung, Nak Gyun

2008-01-01

Kikuchi disease (KD) is a type of benign, self-limiting lymphadenitis, but it has also been associated with hemophagocytic lymphohistiocytosis (HLH). To date, only a few reports have suggested an association between HLH and KD. To report the imaging findings and clinical characteristics of KD accompanied by HLH in children. Five children with a prolonged fever and cervical lymphadenopathy were diagnosed as having HLH accompanied by KD. The authors retrospectively analyzed the clinical characteristics and the imaging findings in these children. The histology of excision biopsy samples of cervical lymph nodes in all children confirmed the diagnosis of KD. HLH was confirmed by bone marrow biopsy and laboratory criteria provided by the Histiocyte Society. The greatest dimension of the enlarged nodes ranged from 0.5 cm to 2.5 cm and the nodes were most frequently located at level V. CT scans visualized perinodal infiltrates in most of the affected cervical nodes (four of five children) and extracervical nodes (three of three children). On enhanced CT scans, nonenhancing necrosis within the affected cervical nodes was noted in three children. KD might be related to HLH in children. Systemic evaluations and follow-up of children with KD might help to identify HLH related to KD. (orig.)

EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease

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John Jacob Kinross-Wright

2018-01-01

Full Text Available Background. Epstein-Barr virus- (EBV- associated lymphoproliferative disease (LPD is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. Case Summary. A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. Conclusion. To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

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Chung, Tae Woong

2007-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

Primary Epstein-Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis.

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Karrasch, Matthias; Felber, Jörg; Keller, Peter M; Kletta, Christine; Egerer, Renate; Bohnert, Jürgen; Hermann, Beate; Pfister, Wolfgang; Theis, Bernhard; Petersen, Iver; Stallmach, Andreas; Baier, Michael

2014-11-01

A case of primary Epstein-Barr virus (EBV) infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH) is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK) cell function, and a lack of hemophagocytosis.

Primary Epstein–Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis

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Karrasch, Matthias; Felber, Jörg; Keller, Peter M.; Kletta, Christine; Egerer, Renate; Bohnert, Jürgen; Hermann, Beate; Pfister, Wolfgang; Theis, Bernhard; Petersen, Iver; Stallmach, Andreas; Baier, Michael

2014-01-01

A case of primary Epstein–Barr virus (EBV) infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH) is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK) cell function, and a lack of hemophagocytosis.

Hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis in the setting of Acquired Immunodeficiency Syndrome (AIDS).

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Asanad, Samuel; Cerk, Brendan; Ramirez, Veronica

2018-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease involving immune system over-activation leading to hemophagocytosis. HLH requires early diagnosis and prompt treatment initiation, especially in patients with Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged male with AIDS and renal failure, who developed HLH secondary to disseminated histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines was deferred and treatment focused instead on anti-fungal therapy. Anti-retroviral therapy followed thereafter.

Hemophagocytic lymphohistiocytosis: a rare diagnosis, an even rarer opportunity to appraise our understanding of the immune system

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José Alexandre Marzagão Barbuto

2015-03-01

Full Text Available The syndrome identified as hemophagocytic lymphohistiocytosis (HLH poses a rather difficult challenge to the physician. HLH was initially described as a familial disorder,1 which was later associated with various genetic defects that affect the cytotoxic machinery of CD8+ T and NK cells,2 but it also occurs sporadically, usually prompted by infections, rheumatic disorders, or neoplasia.3 Although its diagnostic criteria are established, its clinical presentation overlaps with many different conditions, requiring an enhanced awareness of the attending physician in order to reach the diagnosis and to initiate treatment early enough.

Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle.

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Pasqualini, Claudia; Jorini, Mauro; Carloni, Ines; Giangiacomi, Mirella; Cetica, Valentina; Aricò, Maurizio; de Benedictis, Fernando Maria

2014-02-13

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.

Primary Epstein–Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis

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Matthias Karrasch

2014-11-01

Full Text Available A case of primary Epstein–Barr virus (EBV infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK cell function, and a lack of hemophagocytosis.

Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT.

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Kobayashi, R; Tanaka, J; Hashino, S; Ota, S; Torimoto, Y; Kakinoki, Y; Yamamoto, S; Kurosawa, M; Hatakeyama, N; Haseyama, Y; Sakai, H; Sato, K; Fukuhara, T

2014-02-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P=0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

A case of hemophagocytic lymphohistiocytosis presenting as pyrexia of unknown origin

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Indira Madhavan

2015-01-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a potentially fatal hyper inflammatory condition, which occurs as either primary (genetic or secondary (acquired due to impaired or absent function of natural killer cells and cytotoxic cells. Common secondary causes include viral and bacterial infections, autoimmune diseases, and hematological malignancies. Extensive phagocytosis of blood cells by histiocytes in bone marrow, spleen, liver and lymphnodes result in peripheral blood cytopenias, hepatosplenomegaly, and lymphadenopathy. We evaluated a case of pyrexia of unknown origin and found out that he fulfilled the criteria for diagnosing HLH. He was started on immunochemotherapy with etoposide, cyclosporine and steroids, but he succumbed to illness within 2 weeks of treatment. High index of suspicion is needed to diagnose HLH and prompt treatment on diagnosis can be lifesaving.

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

OpenAIRE

Sonke, Gabe; Ludwig, Inge; Oosten, Hannah; Baars, Joke; Meijer, Ellen; Kater, Arnon; Jong, Daphne

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2 abnormal Epstein-Barr virus-associated diseases are seldom reported in individuals other than Japanese children and adolescents. We report a series of 2 adult non-Japanese patients with fatal chronic ac...

Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation.

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Taurisano, Roberta; Maiorana, Arianna; De Benedetti, Fabrizio; Dionisi-Vici, Carlo; Boldrini, Renata; Deodato, Federica

2014-10-01

The lysosomal acid lipase (LAL) is the enzyme responsible of the hydrolysis of cholesteryl esters and triglycerides within endo-lysosomes. Loss of enzyme activity leads to accumulation of cholesteryl esters and triglycerides in the lysosome of most tissues. The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition which may be genetically determined or secondary to infections, malignancies, immune deficiencies, and rheumatologic disorders. So far, some inborn errors of metabolism have been associated with HLH (e.g., lysinuric protein intolerance, Gaucher's disease), and it has been anecdotally described in three WD patients, without any specific pathogenetic hypothesis. Here, we report on a WD patient, showing clear clinical, biochemical, and histological features indicative of HLH. We discuss the pathophysiological role of cholesteryl ester-induced inflammasome activation in macrophages, leading to a secondary HLH. This case indicates that WD can cause secondary HLH and suggests that a careful metabolic workup should be performed when facing to a pediatric patient with HLH.

ANCA Vasculitis and Hemophagocytic Lymphohistiocytosis following a Fecal Microbiota Transplant

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Adam Amlani

2018-01-01

Full Text Available A 69-year-old female with antisynthetase syndrome, a history of multiple recurrent infections, and documented previous negative titres for anti-neutrophil cystoplasmic antibody (ANCA suddenly developed a de novo MPO-ANCA-associated glomerulonephritis three weeks after a fecal microbiota transplantation (FMT for recurrent Clostridium difficile infections. Six months following her FMT and less than two weeks following treatment for urosepsis, she developed severe cholestasis, a markedly elevated ferritin and hypertriglyceridemia. An initial liver biopsy was suggestive of drug-induced liver injury and thus she was treated with supportive care. After she failed to improve, a second liver biopsy supported the diagnosis of hemophagocytic lymphohistiocytosis (HLH. This case highlights difficulties surrounding the early diagnosis of HLH and also questions the role of FMT and/or recurrent infections as a trigger for ANCA-associated vasculitis.

Imaging characteristics of hemophagocytic lymphohistiocytosis

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Fitzgerald, Nancy E.; MacClain, Kenneth L.

2003-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma. (orig.)

Imaging characteristics of hemophagocytic lymphohistiocytosis

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Fitzgerald, Nancy E. [E. B. Singleton Department of Diagnostic Imaging, Texas Children' s Hospital, 6621 Fannin Street, MC 2-2521, TX 77030, Houston (United States); MacClain, Kenneth L. [Texas Children' s Cancer Center, 6701 Fannin, Suite 1510, TX 77030, Houston (United States)

2003-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma. (orig.)

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.

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Virdis, Francesco; Tacci, Sara; Messina, Federico; Varcada, Massimo

2013-11-27

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

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Kozo Nagai

Full Text Available BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2 and UNC13D mutation was in 10 (FHL3. In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5. Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s responsible for FHL remain to be identified.

Hypoalbuminaemia is an independent predictor for hemophagocytic lymphohistiocytosis in childhood Epstein-Barr virus-associated infectious mononucleosis.

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Huang, Shu-Ching; Chen, Jiann-Shiuh; Cheng, Chao-Neng; Yang, Yao-Jong

2012-11-01

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal condition in children with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). This study aimed to identify commonly available clinical and laboratory predictors that might help clinicians decide to perform the bone marrow and immunological tests for HLH in paediatric EBV-associated IM. A retrospective case-control study of patients aged 70% of patients) were fever, lymphadenopathy and hepatomegaly. In addition to the diagnostic criteria of HLH including fever, splenomegaly, cytopenia, hyperferritinaemia, hypertriglyceridemia and/or hypofibrinogenaemia, children with HLH had a significantly higher rate of prolonged fever >10 d, hepatomegaly, jaundice, general malaise, elevated aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and hypoalbuminaemia compared to those with IM (all P < 0.01). Multiple logistic regression confirmed that hypoalbuminaemia (OR = 23.1, P = 0.01) was an independent predictor of paediatric HLH, with a high sensitivity (96%) and a good negative likelihood ratio (0.06) in patients with EBV-associated IM. Hypoalbuminaemia is a unique characteristic and potentially a valuable predictor for HLH in paediatric EBV-associated IM. © 2012 John Wiley & Sons A/S.

Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

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Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

2016-07-01

A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.

Efficacy of Prompt Initiation of Antiretroviral Therapy in the Treatment of Hemophagocytic Lymphohistiocytosis Triggered by Uncontrolled Human Immunodeficiency Virus

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Bryan P. Fitzgerald

2017-01-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART was initiated with darunavir, ritonavir, tenofovir, and emtricitabine. Within one week of initiation of ART, the patient began to improve clinically and hematologically and was stable enough for discharge from the hospital three weeks after starting therapy. This case suggests that treatment with ART in patients with HIV-associated HLH should be considered even in critically ill patients with low CD4 counts.

Dengue fever as a cause of hemophagocytic lymphohistiocytosis.

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Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, Débora Morais; Hirose, Maki; Ferronato, Angela Espósito; Pastorino, Antônio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias

2015-01-01

Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, providing suitable conditions for Aedes aegypti breeding and survival. In Brazil for instance it is from January to June. Dengue may cause marked changes in bone marrow that result in hypocellularity and, consequently, thrombocytopenia and leucopenia, along with an increase in hematocrit, which is secondary to capillary leakage. However, those abnormalities are usually self-limited, and do not warrant further investigations, such as a marrow biopsy or a myelogram. The occurrence of persistent reactive hemophagocytosis is uncommon and usually leads to serious adverse outcomes. The authors report the case of an 8-year old girl complaining of high-grade fever, malaise, headache, abdominal pain and a cutaneous rash. Laboratory examination revealed atypical lymphocytosis on peripheral blood count, hyperbilirrunemia, abnormal liver enzymes and clotting tests. Serology was positive for dengue. Because of the persistence of fever and laboratory examinations were consistent with hemophagocytic lymphohistiocytosis (HLH) a bone marrow aspiration was performed, which confirmed the presence of hemophagocytosis. Hence we report a rare presentation of dengue accompanied by self-limited HLH that hopefully evolve to favorable outcome.

The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.

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Qian, Yaping; Johnson, Judith A; Connor, Jessica A; Valencia, C Alexander; Barasa, Nathaniel; Schubert, Jeffery; Husami, Ammar; Kissell, Diane; Zhang, Ge; Weirauch, Matthew T; Filipovich, Alexandra H; Zhang, Kejian

2014-06-01

The mutations in UNC13D are responsible for familial hemophagocytic lymphohistiocytosis (FHL) type 3. A 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in UNC13D were recently reported in European and Asian FHL3 patients. We sought to determine the prevalence of these three non-coding mutations in North American FHL patients and evaluate the significance of examining these new mutations in genetic testing. We performed DNA sequencing of UNC13D and targeted analysis of these three mutations in 1,709 North American patients with a suspected clinical diagnosis of hemophagocytic lymphohistiocytosis (HLH). The 253-kb inversion, intronic mutations c.118-308C > T and c.118-307G > A were found in 11, 15, and 4 patients, respectively, in which the genetic basis (bi-allelic mutations) explained 25 additional patients. Taken together with previously diagnosed FHL3 patients in our HLH patient registry, these three non-coding mutations were found in 31.6% (25/79) of the FHL3 patients. The 253-kb inversion, c.118-308C > T and c.118-307G > A accounted for 7.0%, 8.9%, and 1.3% of mutant alleles, respectively. Significantly, eight novel mutations in UNC13D are being reported in this study. To further evaluate the expression level of the newly reported intronic mutation c.118-307G > A, reverse transcription PCR and Western blot analysis revealed a significant reduction of both RNA and protein levels suggesting that the c.118-307G > A mutation affects transcription. These specified non-coding mutations were found in a significant number of North American patients and inclusion of them in mutation analysis will improve the molecular diagnosis of FHL3. © 2014 Wiley Periodicals, Inc.

Wolman disease in patients with familial hemophagocytic ...

African Journals Online (AJOL)

Major signs and symptoms include hepatomegaly, splenomegaly, anemia, leucopenia or thrombocytopenias which resemble many inborn errors of metabolism and lysosomal storage diseases in which hemophagocytic lymphohistiocytosis has also been reported as a secondary association. Case reports: We report three ...

Genetics Home Reference: familial hemophagocytic lymphohistiocytosis

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... lymphohistiocytosis. Haematologica. 2010 Apr;95(4):538-41. doi: 10.3324/haematol.2009.019562. Citation on PubMed ... Clin Immunol. 2011 Dec;11(6):512-6. doi: 10.1097/ACI.0b013e32834c22f5. Review. Citation on PubMed ...

Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause.

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Jing-Shi, Wang; Yi-Ni, Wang; Lin, Wu; Zhao, Wang

2015-05-01

Our aim was to evaluate the clinical value of splenectomy as a treatment for relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause in adults. We retrospectively reviewed the clinical data from medical records of 19 adults with relapsed HLH of unknown cause treated with splenectomy in our institution from June 2007 to March 2014. To rule out possible underlying diseases, including infection, autoimmune disease, neoplasms, and primary HLH, the patients had undergone examinations including F18 fluoro-2-deoxyglucose positron emission tomography/computed tomography, HLH-associated gene defects, and lymph node biopsies. Twelve patients (63.2%) achieved partial responses (PR), whereas seven patients (36.8%) had no response (NR) prior to splenectomy. Infection and hemorrhage were the main complications of splenectomy. Eighteen cases were evaluable after follow-up. Seven cases with histopathologic diagnoses of lymphoma had received chemotherapy, four of whom had achieved complete responses (CR), one PR, and two NR. Maintenance treatment was ceased 2 or 3 months after splenectomy in the other 11 cases, five of whom had CR, four PR, and two NR. Eleven of 18 cases (61.1%) survived with a median follow-up of 25 months (range 3-79 months) for survivors. Twelve- and 36-month progression-free survival rates were 48 and 24%, respectively; 12- and 36-month overall survival rates were 57 and 25%, respectively. Median survival time was 22 months. Our results indicate splenectomy may be an effective means of diagnosis and treatment of relapsed HLH of unknown cause. Further study is required to establish the mechanism and value of splenectomy in this disease.

Diagnosing XLP1 in patients with hemophagocytic lymphohistiocytosis.

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Meazza, Raffaella; Tuberosa, Claudia; Cetica, Valentina; Falco, Michela; Parolini, Silvia; Grieve, Sam; Griffiths, Gillian M; Sieni, Elena; Marcenaro, Stefania; Micalizzi, Concetta; Montin, Davide; Fagioli, Franca; Moretta, Alessandro; Mingari, Maria C; Moretta, Lorenzo; Notarangelo, Luigi D; Bottino, Cristina; Aricò, Maurizio; Pende, Daniela

2014-12-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, heterogeneous, hyperinflammmatory disorder. Prompt identification of inherited forms resulting from mutation in genes involved in cellular cytotoxicity can be crucial. X-linked lymphoproliferative disease 1 (XLP1), due to mutations in SH2D1A (Xq25) encoding signaling lymphocyte activation molecule-associated protein (SAP), may present with HLH. Defective SAP induces paradoxical inhibitory function of the 2B4 coreceptor and impaired natural killer (NK) (and T) cell response against EBV-infected cells. To characterize a cohort of patients with HLH and XLP1 for SAP expression and 2B4 function in lymphocytes, proposing a rapid diagnostic screening to direct mutation analysis. We set up rapid assays for 2B4 function (degranulation or (51)Cr-release) to be combined with intracellular SAP expression in peripheral blood NK cells. We studied 12 patients with confirmed mutation in SH2D1A and some family members. The combined phenotypic/functional assays allowed efficient and complete diagnostic evaluation of all patients with XLP1, thus directing mutation analysis and treatment. Nine cases were SAP(-), 2 expressed SAP with mean relative fluorescence intensity values below the range of healthy controls (SAP(dull)), and 1, carrying the R55L mutation, was SAP(+). NK cells from all patients showed inhibitory 2B4 function and defective killing of B-EBV cells. Carriers with SH2D1A mutations abolishing SAP expression and low percentage of SAP(+) cells showed neutral 2B4 function at the polyclonal NK cell level. Three novel SH2D1A mutations have been identified. Study of SAP expression is specific but may have insufficient sensitivity for screening XLP1 as a single tool. Combination with 2B4 functional assay allows identification of all cases. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Infection Associated Secondary Hemophagocytic Lymphohistiocytosis in Sepsis Syndromes - A Tip of an Iceberg.

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Agarwal, Arun; Agarwal, Aakanksha

2017-10-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare, underdiagnosed, fatal and devastating hyperinflammatory syndrome that has gained increasing recognition over the past decade. Patients with HLH present with clinical and laboratory evidence of uncontrolled inflammation. Delay in diagnosis and management inevitably leads to a rapidly progressive and fatal course. In this case series, we present 7 cases of secondary HLH (sHLH) in adults with their presentation, course, and outcomes. We retrospectively looked at the 7 cases of secondary HLH who were diagnosed and managed in our institute between January 2013 and august 2015. Medical records were retrieved from medical records department and data analyzed and tabulated. The median age at diagnosis was 35 years (age range 26-72 years). Diagnosis was based on HLH 2004 diagnostic criteria. We report profile of 7 adult patients with sHLH. All patients had a short history of illness (<2 weeks) and presented uniformly with prolonged fever, bi or trilineage cytopenia and multiorgan dysfunction syndrome (MODS) at admission or developed MODS during the course of their illness. None of them had prediagnosed HLH. All patients fulfilled 5 to 6 of 8 criteria as per HLH 2014 diagnostic criteria. The median length of hospital stay was 12 days (range 7-50 days) and the median time to diagnosis was 5 days (range 3 to 21 days). Mortality was 57%. HLH is a rare and under-diagnosed clinical syndrome and is rapidly fatal if not diagnosed and managed timely. The cases reported in literature probably represent a tip of an iceberg of large number of undiagnosed cases mostly labeled as sepsis with MODS in critical care units. sHLH should be suspected in any patient who present with persistent and prolonged fever, transaminitis, cytopenia, and high serum Ferritin or dramatically rising serial serum Ferritin. Early diagnosis and prompt aggressive treatment are vital for patients' survival and favorable outcome.

Structural and functional analysis of perforin mutations in association with clinical data of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) patients

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An, Omer; Gursoy, Attila; Gurgey, Aytemiz; Keskin, Ozlem

2013-01-01

Perforin plays a key role in the immune system via pore formation at the target cell membrane in the elimination of virus-infected and transformed cells. A vast number of observed mutations in perforin impair this mechanism resulting in a rare but fatal disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Here we report a comprehensive in silico structural analysis of a collection of 76 missense perforin mutations based on a proposed pore model. In our model, perforin monomers oligomerize having cyclic symmetry in consistent with previously found experimental constraints yet having flexibility in the size of the pore and the number of monomers involved. Clusters of the mutations on the model map to three distinct functional regions of the perforin. Calculated stability (free energy) changes show that the mutations mainly destabilize the protein structure, interestingly however, A91V polymorphism, leads to a more stable one. Structural characteristics of mutations help explain the severe functional consequences on perforin deficient patients. Our study provides a structural approach to the mutation effects on the perforin oligomerization and impaired cytotoxic function in FHL2 patients. PMID:23592409

Iatrogenic T-Cell Lymphoma with Associated Hemophagocytic Lymphohistiocyotsis in a Patient with Long-Standing Rheumatoid Arthritis

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X. A. Andrade

2018-01-01

Full Text Available Patients with rheumatoid arthritis are at increased risk of hematological malignancies, especially when exposed to immunosuppressive therapy. The mechanisms of lymphomagenesis remain poorly understood but factors implicated include high disease activity, exposure to antitumoral necrosis factor medications, and Epstein–Barr virus infection. Lymphoid malignancies of T-cell origin are uncommon in patients with rheumatoid arthirits. Clinical presentation with associated hemophagocytic lymphohistiocyotsis is rare and confers a poor prognosis. This case report illustrates a case of a patient with long-standing rheumatoid arthritis and an iatrogenic peripheral T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis who achieved a complete response after intensive chemotherapy.

Successful management of a complicated clinical crisis: A patient with left-sided endocarditis and secondary hemophagocytic lymphohistiocytosis: a rare case report and literature review.

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Xu, Peipei; Zeng, Hui; Zhou, Min; Ouyang, Jian; Chen, Bing; Zhang, Qiguo

2017-12-01

Hemophagocytic lymphohistiocytosis (HLH) secondary to methicillin-resistant Staphylococcus epidermidis (MRSE)-related left-sided infectious endocarditis had never been reported before. In the last decade, daptomycin, a novel lipopeptide antibiotic, showed its excellent role in anti-Gram-positive bacteria, including soft tissue infection, bloodstream and deep tissueinfection. An Asian women under sever condition due to the cooccurrence of HLH and MRSE-related endocarditis while also be allergic to vancomycin. The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. IE was made on March 27according to the modified Duke criteria. HLH was diagnosed too. The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. The patient was healthy andstable when we published this case. This case proves high-dose daptomycin monotheraphy could be used as an effective alternative regimen for vancomycin in treating MRSE-related left-sided endocarditis and highlight the importance of early diagnosis and appropriate management for HLH. Furthermore, our work suggests an MDT model as a practical strategy in managing similar clinical situation. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Characterization of Epstein-Barr virus (EBV) BZLF1 gene promoter variants and comparison of cellular gene expression profiles in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis.

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Imajoh, Masayuki; Hashida, Yumiko; Murakami, Masanao; Maeda, Akihiko; Sato, Tetsuya; Fujieda, Mikiya; Wakiguchi, Hiroshi; Daibata, Masanori

2012-06-01

Epstein-Barr virus (EBV) genotypes can be distinguished based on gene sequence differences in EBV nuclear antigens 2, 3A, 3B, and 3C, and the BZLF1 promoter zone (Zp). EBV subtypes and BZLF1 Zp variants were examined in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis. The results of EBV typing showed that samples of infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis all belonged to EBV type 1. However, sequencing analysis of BZLF1 Zp found three polymorphic Zp variants in the same samples. The Zp-P prototype and the Zp-V3 variant were both detected in infectious mononucleosis and chronic active EBV infection. Furthermore, a novel variant previously identified in Chinese children with infectious mononucleosis, Zp-V1, was also found in 3 of 18 samples of infectious mononucleosis, where it coexisted with the Zp-P prototype. This is the first evidence that the EBV variant distribution in Japanese patients resembles that found in other Asian patients. The expression levels of 29 chronic active EBV infection-associated cellular genes were also compared in the three EBV-related disorders, using quantitative real-time reverse transcription polymerase chain reaction analysis. Two upregulated genes, RIPK2 and CDH9, were identified as common specific markers for chronic active EBV infection in both in vitro and in vivo studies. RIPK2 activates apoptosis and autophagy, and could be responsible for the pathogenesis of chronic active EBV infection. Copyright © 2012 Wiley Periodicals, Inc.

Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

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Ellis, Esther M.; Pérez-Padilla, Janice; González, Liza; Poole-Smith, B. Katherine; Lebo, Emmaculate; Baker, Charlotte; Delorey, Mark J.; Torres-Velasquez, Brenda; Ochoa, Eduardo; Rivera-Garcia, Brenda; Díaz-Pinto, Hector; Clavell, Luis; Puig-Ramos, Anabel; Janka, Gritta E.; Tomashek, Kay M.

2016-01-01

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury. PMID:27556807

Immunologic difference between hypersensitivity to mosquito bite and hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection.

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Wen-I Lee

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB, a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV, may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients and 14 HMB episodes (4 patients, there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+ lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+ increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies.

Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy.

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Messina, Chiara; Zecca, Marco; Fagioli, Franca; Rovelli, Attilio; Giardino, Stefano; Merli, Pietro; Porta, Fulvio; Aricò, Maurizio; Sieni, Elena; Basso, Giuseppe; Ripaldi, Mimmo; Favre, Claudio; Pillon, Marta; Marzollo, Antonio; Rabusin, Marco; Cesaro, Simone; Algeri, Mattia; Caniglia, Maurizio; Di Bartolomeo, Paolo; Ziino, Ottavio; Saglio, Francesco; Prete, Arcangelo; Locatelli, Franco

2018-06-01

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 + cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hemophagocytic Lymphohistiocytosis Secondary to Unknown Underlying Hodgkin Lymphoma Presenting with a Cholestatic Pattern of Liver Injury

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A.L. Booth

2018-04-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is an uncommon disease that often presents with nonspecific findings. A high index of suspicion is necessary to make a prompt diagnosis and prevent fatal disease. A 45-year-old man presented with fever, hypotension, abdominal pain, nausea, and vomiting. Imaging showed hepatosplenomegaly and laboratory tests revealed pancytopenia, increased ferritin, and a cholestatic pattern of injury with elevated alkaline phosphatase and total bilirubin. Due to a history of Crohn disease, systemic lupus erythematous, and rheumatoid arthritis, the patient was on immunosuppressants, including infliximab. After multiple negative cultures, persistent fever, and days of empiric broad spectrum antibiotics, our differential shifted to fever of unknown origin. A liver wedge biopsy revealed areas of sinusoidal dilatation with enlarged, activated macrophages containing erythrocytes and intracytoplasmic iron, consistent with hemophagocytosis due to HLH. The portal tracts showed mixed lymphoplasmacytic inflammation, a prominent bile ductular reaction, periportal fibrosis, and scattered large cells with occasional binucleation and prominent nucleoli. These cells stained positive for Epstein-Barr virus encoding region in situ hybridization, PAX5, CD15, and CD30, and hepatic involvement by classic Hodgkin lymphoma was diagnosed and determined to be the cause of the HLH and cholestatic pattern of injury. Simultaneously, a bone marrow biopsy showed diffuse involvement by Hodgkin lymphoma with a similar staining pattern. Aggressive treatment failed and the patient succumbed to multiorgan failure. HLH is a rare, potentially fatal disease, with nonspecific signs and symptoms, and should be considered in any patient presenting with fever and pancytopenia, especially if they are immune compromised.

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group.

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Moritake, Hiroshi; Kamimura, Sachiyo; Nunoi, Hiroyuki; Nakayama, Hideki; Suminoe, Aiko; Inada, Hiroko; Inagaki, Jiro; Yanai, Fumio; Okamoto, Yasuhiro; Shinkoda, Yuichi; Shimomura, Maiko; Itonaga, Nobuyoshi; Hotta, Noriko; Hidaka, Yasufumi; Ohara, Osamu; Yanagimachi, Masakatsu; Nakajima, Noriko; Okamura, Jun; Kawano, Yoshifumi

2014-07-01

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu-Yamaguchi Children's Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

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2017-08-29

Acute Lymphoblastic Leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hemophagocytic Lymphohistiocytosis (HLH); Familial Hemophagocytic Lymphohistiocytosis (FLH); Viral-associated Hemophagocytic Syndrome (VAHS); X-linked Lymphoproliferative Disease (XLP)

Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein

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Laura eChiossone

2012-08-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-γ and TNFα is present in serum. In animal models of the disease, IFN-γ and TNF-α have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-γ and TNF-α have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP resulting in an excess of free IL-18. Here we studied whether IL-18BP could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock-out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18BP treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-γ and TNF-α production by CD8+ T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18BP is beneficial in an animal model of HLH and in combination with anti-infectious therapy may be a promising strategy to treat HLH patients.

Hemophagocytic lymphohistiocytosis and Pelger-Huët anomaly associated with colchicine intoxication

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Baris Malbora

2014-06-01

Full Text Available Colchicine is frequently used in the treatment of familial Mediterranean fever (FMF. First symptoms of colchicine intoxication are gastrointestinal disturbances, such as abdominal cramps, diarrhea, pancytopenia and so on. Herein, we report a female FMF patient with pancytopenia and hemophagocytic lymphohitiocytosis (HLH, following colchicine intoxication for committing suicide. To our knowledge, this is the first reported case of a patient with HLH associated with colchicine intoxication.

A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.

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Bordbar, Mohammad Reza; Modarresi, Farzaneh; Farazi Fard, Mohammad Ali; Dastsooz, Hassan; Shakib Azad, Nader; Faghihi, Mohammad Ali

2017-05-03

Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.

[The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].

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Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z

2016-07-01

To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

Association of Monoclonal Expansion of Epstein-Barr Virus-Negative CD158a+ NK Cells Secreting Large Amounts of Gamma Interferon with Hemophagocytic Lymphohistiocytosis▿

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López-Álvarez, María R.; Martínez-Sánchez, María V.; Salgado-Cecilia, María G.; Campillo, José A.; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L.; Bas, Águeda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M.; Álvarez-López, María R.; Minguela, Alfredo

2009-01-01

We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

Secondary Hemophagocytic Syndrome: The Importance of Clinical Suspicion

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Cristina Oliveira

2014-01-01

Full Text Available Hemophagocytic syndrome is a rare and potentially fatal disorder characterized by pathological immune activation associated with a primary familial disorder, genetic mutations, or occurring as a sporadic condition. The latter can be secondary to infections, malignancies, or autoimmune diseases. Clinically, patients present signs of severe inflammation, with unremitting fever, cytopenias, spleen enlargement, phagocytosis of bone marrow elements, hypertriglyceridemia, and hypofibrinogenemia. Increased suspicion is determinant to timely initiate treatment in an attempt to alter the natural history. The authors present three clinical cases of this syndrome, with a brief review of the diagnostic criteria and treatment.

A case report and clinical approach to silver blonde hair

African Journals Online (AJOL)

Sana Durrani

2015-09-29

Sep 29, 2015 ... Abstract Griscelli syndrome type 2 is a rare autosomal recessive disease caused by mutations in the. RAB27A gene. It is characterized by pigmentary dilution of the skin and hair causing silvery gray hair, hemophagocytic lymphohistiocytosis and characteristic light microscopy findings in scalp hair.

Elevation of CD16+CD56+ NK-cells and down-regulation of serum interleukin-21 (IL-21) and IL-1α after splenectomy in relapsed hemophagocytic lymphohistiocytosis of unknown cause.

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Wang, Jingshi; Han, Wei; Gao, Zhuo; Wang, Yini; Wu, Lin; Zhang, Jia; Lai, Wenyuan; Wang, Zhao

2017-09-01

Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy. We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis. During the period from June 2006 to June 2016, we enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were available for analysis. Results showed a significant increase in both percentage of CD16 + CD56 + NK cells (P = 0.003) and NK cell activity (P = 0.028) at 24 wk after splenectomy compared to their baseline pre-surgery levels. We also examined seven patients for the changes in cytokine levels before and after splenectomy and found that IL-21 and IL-1α decreased at 4 wk after splenectomy (P splenectomy had significantly longer survival (P = 0.001) compared to the 24 patients with relapsed HLH of unknown cause who were also determined as NR but not treated by splenectomy. Splenectomy can improve clinical symptoms and survival of patients with relapsed HLH of unknown cause. The mechanism is likely related to the changes in percent NK cells and cytokines (IL-21 and IL-1α) after surgery.

Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation.

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Fernández, Alexandra Arteaga; de Velasco Pérez, David Fernández; Fournier, M C Jiménez; Moreno Del Prado, J C; Torras, B Paraíso; Cañete Palomo, M L

2017-01-01

Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.

Hemophagocytic syndrome in classic dengue fever

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Sayantan Ray

2011-01-01

Full Text Available A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnostic criteria of the HLH 2004 protocol of the Histiocyte Society. The patient recovered with corticosteroid therapy. A review of literature revealed only a handful of case reports that showed the evidence that this syndrome is caused by dengue virus. Our patient is an interesting case of hemophagocytic syndrome associated with classic dengue fever and contributes an additional case to the existing literature on this topic. This case highlights the need for increased awareness even in infections not typically associated with hemophagocytic syndrome.

Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation

Directory of Open Access Journals (Sweden)

Alexandra Arteaga Fernández

2017-01-01

Full Text Available Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.

The frequency of A91V in the perforin gene and the effect of tumor necrosis factor-α promoter polymorphism on acquired hemophagocytic lymphohistiocytosis

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Hamza Okur

2011-06-01

Full Text Available Objective: Numerous acquired etiological factors, such as infections, malignancies, and collagen tissue disorders, are involved in the development of acquired hemophagocytic lymphohistiocytosis (AHLH. Not everyone with the same etiological factors developments AHLH, which suggests the role of additional genetic or environmental predisposing factors that remain to be identified. Materials and Methods: Perforin gene A91V missense transition (C>T change at position 272 in exon 2 of the perforin gene and TNF-α gene promoter-1031 T>C nucleotide substitution are 2 candidate genetic predisposing factors due to their potential to alter inflammatory responses. In the present study these changes were investigated in healthy controls and AHLH patients.Results: A91V transition was observed in 7 of the 159 (4.4% controls. Among the 44 AHLH patients, 5 (11.3% were heterozygous and the difference in the frequency of A91V transition, although striking (odds ratio: 2.8, was not statistically significant (p=0.09. All A91V-positive patients had infection. TNF-α-1031 T>C polymorphism was examined in 164 healthy controls and 40 AHLH patients, and the CC risk-elevating genotype was noted in 7 (4.3% of the controls and 1 (2.5% of the AHLH patients. The frequency of C and T alleles was 22.5% (n=18 and 77.5% (n=62 among the AHLH patients, and 22% (n=72 and 78% (n=259 among the controls, respectively. There wasn’t a statistically significant difference between the groups in terms of allele frequencies (p>0.05.Conclusion: The present results indicate that compared to controls, A91V mutation was 2.8-fold more prevalent (according to the odds ratio in the AHLH patients. A91V mutation is not uncommon in the general population and increases the risk of AHLH in patients with an underlying condition, especially those with an underlying infection.

Nasopharyngeal Carcinoma Associated with Hemophagocytic Lymphohistiocytosis

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Hsu Wu

2015-03-01

Conclusions: HLH is a disease with high fatality. Whenever there is a degree of clinical suspicion for HLH, etoposide-based chemotherapy should be started as soon as possible, and the underlying causes of the disease should be treated. We report this patient with NPC and HLH, which can be associated with either EBV or NPC. We treated both etiologies, and the patient's symptoms and liver function improved. The interactions between EBV, NPC, and HLH are interesting and merit further investigation.

Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study.

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Cai, Guilan; Wang, Yini; Liu, Xiaojing; Han, Yanfei; Wang, Zhao

2017-08-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system (CNS). Neurological manifestations of HLH have been recognized in different studies with children, but they remain relatively ill-defined in adults with HLH. From March 2008 to October 2014, 289 adult patients with HLH were admitted to our center. Clinical, radiological, and cerebral spinal fluid (CSF) data of the patients with CNS involvement were reviewed, and a retrospective study in our single-center was carried out. CNS involvement was observed in 29 patients (10%) either in their diagnosis process or during disease course. CNS symptoms included disturbance of consciousness, cranial nerve palsies, seizures, headache, limb paralysis, irritability, meningism, and memory loss. CSF analysis was conducted in 17 patients (59%). Among them, 11 patients (65%) were reported as having abnormal CSF. Neuroradiological studies were performed in 25 patients (86%). Among the 13 cases that underwent CT scan, one patient hemorrhaged. Single or multiple hypodense foci were detected in the other 2 patients. Magnetic resonance imaging (MRI) abnormalities were found in 15 patients, including focal lesions in cortical and adjacent subcortical regions with or without variable nodular or ring contrast-enhancement, multiple lesions in white matter, diffuse white matter signal changes, and meningeal enhancement. Basal ganglia, cerebellum, and brainstem lesions were also observed. CNS involvement could also be found in adult patients with HLH, but not as frequent as it was in children. The clinical manifestations could be diversified. By carrying out rigorous CNS examinations, an early diagnosis could be made and it was of the utmost importance for the prevention of further lesions.

Endoperoxidation, hyperprostaglandinemia, and hyperlipidemia in a case of erythrophagocytic lymphohistiocytosis. Reversal with VP-16 and indomethacin.

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Brown, R E; Bowman, W P; D'Cruz, C A; Pick, T E; Champion, J E

1987-11-15

Clinicopathologic and histopathologic evidence of both endoperoxidation with hyperprostaglandinemia and hyperlipidemia in a 5-week-old infant with a hemophagocytic syndrome is reported. Institution of histiocytolytic (VP-16) and cyclo-oxygenase inhibitor (indomethacin) therapies returned the prostaglandin levels and lipid profile to a nearly normal state coincidental with clinical recovery. It appears that by reducing the cell mass of histiocytes and controlling the over-production of prostaglandins, some types of hemophagocytic syndrome can be reversed.

BMT Abatacept for Non-Malignant Diseases

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2018-05-16

Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

Secondary Hemophagocytic Syndrome Associated with Herpes Virus Infections

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S. R. Rodionovskaya

2015-01-01

Full Text Available Hemophagocytic syndrome is one of the complications of herpes virus infections. Here, we describe the case of a 8—year-old male with secondary hemophagocytic syndrome. The disease was diagnosed in the early stages. The patient received treatment with dexamethasone, intravenous immunoglobulin, which has led to a weakening of the ignition and the suppression of the disease with rapid treatment.

CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

Science.gov (United States)

2017-07-13

Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

X-linked inhibitor of apoptosis (XIAP) deficiency

DEFF Research Database (Denmark)

Speckmann, C.; Lehmberg, K.; Albert, M.H.

2013-01-01

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant...

Acute or chronic life-threatening diseases associated with Epstein-Barr virus infection.

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Okano, Motohiko; Gross, Thomas G

2012-06-01

Infectious mononucleosis (IM) is one of the representative, usually benign, acute diseases associated with primary Epstein-Barr virus (EBV) infection. IM is generally self-limiting and is characterized mostly by transient fever, lymphadenopathy and hepatosplenomegaly. However, very rarely primary EBV infection results in severe or fatal conditions such as hemophagocytic lymphohistiocytosis together with fulminant hepatitis designated as severe or fatal IM or EBV-associated hemophagocytic lymphohistiocytosis alone. In addition, chronic EBV-associated diseases include Burkitt's lymphoma, undifferentiated nasopharyngeal carcinoma, Hodgkin lymphoma, T-cell lymphoproliferative disorder (LPD)/lymphoma, natural killer-cell LPD including leukemia or lymphoma, gastric carcinoma, pyothorax-associated lymphoma and senile B-cell LPD as well as chronic active EBV infection and LPD/lymphoma in patients with immunodeficiency. The number of chronic life-threatening diseases linked to the EBV infection is increasingly reported and many of these diseases have a poor prognosis. This review will focus on the historical, pathogenetic, diagnostic, therapeutic and prophylactic issues of EBV-associated life-threatening diseases.

A rare complication of CMV infection in Crohn's disease - hemophagocytic syndrome: a case report.

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Pop, Corina Silvia; Becheanu, Gabriel; Calagiu, Dorina; Jantea, Petruţa-Violeta; Rădulescu, Dragoş Mihai; Pariza, George; Mavrodin, Carmen-Iuliana; Bold, Adriana; Costache, Adrian; Nemeş, Roxana Maria

2015-01-01

We report a case of CMV (cytomegalovirus) infection in a Crohn's disease patient, resulting in severe hemophagocytic syndrome and death. A 63-year-old man with a 10-year history of ileal and colonic Crohn's disease presented with general malaise, loss of appetite and weight loss over the last month. He was in clinical remission for two years, with maintenance therapy 5-Aminosalicylic acid (5-ASA)-derived Mesalamine. The patient had no prior immunomodulators or suppressive treatment. A colonoscopy was performed and we found appearance suggestive of active Crohn's disease, confirmed by histopathological examination. A diagnosis of an exacerbation of Crohn's disease was established. Although the specific treatment was initiated, patient's general condition degraded progressively and diarrheal stools appeared, followed by an episode of massive gastrointestinal bleeding - hematochezia. We performed a new colonoscopy and the pathological examination revealed Crohn's ileocolitis with superimposed CMV infection. Despite the initiation of Ganciclovir alongside with other intensive care measures, he increasingly deteriorated and chest X-ray confirmed multilobar pneumonia. The occurrence of rapidly progressing pancytopenia and evidence for disseminated intravascular coagulopathy as well as hyperferritinemia, raised the suspicion of hemophagocytic syndrome confirmed by bone marrow aspiration. Hence, CMV-associated hemophagocytic syndrome in the context of recent corticotherapy for Crohn's disease was established. There is enough evidence that supports the gravity of the CMV infection in the case of inflammatory bowel disease (IBD) patients, especially the ones on immunomodulator treatment. The hemophagocytic syndrome reactively occurs in patients with infections in cases of immunodeficiency, displaying a hematological aspect of multiple organ dysfunction syndrome.

Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency.

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Soheili, Tayebeh; Durand, Amandine; Sepulveda, Fernando E; Rivière, Julie; Lagresle-Peyrou, Chantal; Sadek, Hanem; de Saint Basile, Geneviève; Martin, Samia; Mavilio, Fulvio; Cavazzana, Marina; André-Schmutz, Isabelle

2017-12-26

Patients with mutations in the UNC13D gene (coding for Munc13-4 protein) suffer from familial hemophagocytic lymphohistiocytosis type 3 (FHL3), a life-threatening immune and hyperinflammatory disorder. The only curative treatment is allogeneic hematopoietic stem cell (HSC) transplantation, although the posttreatment survival rate is not satisfactory. Here, we demonstrate the curative potential of UNC13D gene correction of HSCs in a murine model of FHL3. We generated a self-inactivating lentiviral vector, used it to complement HSCs from Unc13d -deficient (Jinx) mice, and transplanted the cells back into the irradiated Jinx recipients. This procedure led to complete reconstitution of the immune system (ie, to wild-type levels). The recipients were then challenged with lymphocytic choriomeningitis virus to induce hemophagocytic lymphohistiocytosis (HLH)-like manifestations. All the clinical and biological signs of HLH were significantly reduced in mice having undergone HSC UNC13D gene correction than in nontreated animals. This beneficial effect was evidenced by the correction of blood cytopenia, body weight gain, normalization of the body temperature, decreased serum interferon-γ level, recovery of liver damage, and decreased viral load. These improvements can be explained by the restoration of the CD8 + T lymphocytes' cytotoxic function (as demonstrated here in an in vitro degranulation assay). Overall, our results demonstrate the efficacy of HSC gene therapy in an FHL-like setting of immune dysregulation.

Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis.

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Su, I J; Hsu, Y H; Lin, M T; Cheng, A L; Wang, C H; Weiss, L M

1993-09-15

The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

Wolman disease in patients with familial hemophagocytic ...

African Journals Online (AJOL)

Solaf Elsayed

2015-09-26

Sep 26, 2015 ... Marine Gil b ... many inborn errors of metabolism and lysosomal storage diseases in which hemophagocytic ... The diagnosis of secondary HLH is usually made in association with infection by viruses, bacteria, fungi, or para-.

Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome.

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Wan Jamaludin, Wan Fariza; Periyasamy, Petrick; Wan Mat, Wan Rahiza; Abdul Wahid, S Fadilah

2015-08-01

Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin. Copyright © 2015 Elsevier B.V. All rights reserved.

An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits.

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Hayashi, K; Ohara, N; Teramoto, N; Onoda, S; Chen, H L; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yates, J; Akagi, T

2001-04-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.

Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

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Ameli, Fereshteh; Ghafourian, Firouzeh; Masir, Noraidah

2014-08-27

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

Wolman disease in patients with familial hemophagocytic lymphohistiocytosis (FHL negative mutations

Directory of Open Access Journals (Sweden)

Solaf Elsayed

2016-07-01

Conclusion: Wolman disease should be excluded in patients with clinical and laboratory characteristics of FHL and negative molecular testing especially if the fever is not prominent and is associated with relatively huge hepatomegaly and/or severe failure to thrive.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome).

Science.gov (United States)

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation.

An Animal Model for Human EBV-Associated Hemophagocytic Syndrome

Science.gov (United States)

Hayashi, Kazuhiko; Ohara, Nobuya; Teramoto, Norihiro; Onoda, Sachiyo; Chen, Hong-Li; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Yates, John; Akagi, Tadaatsu

2001-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS. PMID:11290571

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

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Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

2014-04-01

Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

Rabbit Model for Human EBV-Associated Hemophagocytic Syndrome (HPS)

Science.gov (United States)

Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a “starry sky” pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

Advances in basic and clinical immunology in 2016.

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Chinen, Javier; Badran, Yousef R; Geha, Raif S; Chou, Janet S; Fried, Ari J

2017-10-01

Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T and B cells, including cytokines and proteins involved in the actin cytoskeleton. Regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohistiocytosis. The role of prenylation in patients with mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology, as well as new approaches of whole-genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT); B-cell CLL/lymphoma 11B (BCL11B); RGD, leucine-rich repeat, tropomodulin domain, and proline-rich domain-containing protein (RLTPR); moesin; and Janus kinase 1 (JAK1). Trials of hematopoietic stem cell transplantation and gene therapy for primary immunodeficiency have had relative success; the use of autologous virus-specific cytotoxic T cells has proved effective as well. New medications are being explored, such as pioglitazone, which is under study for its role in enhancing the oxidative burst in patients with chronic granulomatous disease. Development of vaccines for HIV infection continues to provide insight into the immune response against a virus with an extraordinary mutation rate. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Serial brain MRI findings in CNS involvement of familial erythrophagocytic lymphohistiocytosis: a case report

International Nuclear Information System (INIS)

Cho, Kyung Soo; Yoo, Jeong Hyun; Suh, Jeong Soo; Ryu, Kyung Ha; Hong, Ki Sook; Kim, Hak Jin

2002-01-01

Familial erythrophagocytic lymphohistiocytosis is a fatal early childhood disorder characterized by multiorgan lymphohistiocytic infiltration and active hemophagocytosis. Involvement of the central nervous system (CNS) is not uncommon and is characterized by rapidly progressive tissue damage affecting both the gray and white matter. We encountered a case of familial erythrophagocytic lymphohistiocytosis with CNS involvement. Initial T2-weighted MRI of the brain demonstrated high signal intensity in the right thalamus, though after chemotherapy, which led to the relief of neurologic symptoms, this disappeared. After four months. however, the patient's neurologic symptoms recurred, and follow-up T2-weighted MR images showed high signal intensity in the thalami, basal ganglia, and cerebral and cerebellar white matter. Brain MRI is a useful imaging modality for the evaluation of CNS involvement and monitoring the response to treatment

Dengue fever as a cause of hemophagocytic lymphohistiocytosis

OpenAIRE

Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, D?bora Morais; Hirose, Maki; Ferronato, Angela Esp?sito; Pastorino, Ant?nio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias

2015-01-01

Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, pro...

PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

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Patiroglu, T; Akar, H H; Unal, E; Chiang, S C; Schlums, H; Tesi, B; Ozkars, M Y; Karakukcu, M

2016-01-01

Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

Rubella associated with hemophagocytic syndrome. First report in a male and review of the literature

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Makram Koubaa

2012-08-01

Full Text Available A 22-year-old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C, generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positif and the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have rubella-associated hemophagocytic syndrome. We report herein the first case in a man and the sixth case of rubella-associated hemophagocytic syndrome in the literature by search in Pub Med till March 2012.

Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5)

DEFF Research Database (Denmark)

Pagel, Julia; Beutel, Karin; Lehmberg, Kai

2012-01-01

the genetic and clinical spectrum of FHL5, we analyzed a cohort of 185 patients with suspected FHL for mutations in STXBP2. We detected biallelic mutations in 37 patients from 28 families of various ethnic origins. Missense mutations and mutations affecting 1 of the exon 15 splice sites were the predominant...... changes detectable in this cohort. Patients with exon 15 splice-site mutations (n = 13) developed clinical manifestations significantly later than patients with other mutations (median age, 4.1 year vs 2 months) and showed less severe impairment of degranulation and cytotoxic function of NK cells and CTLs....... Patients with FHL5 showed several atypical features, including sensorineural hearing deficit, abnormal bleeding, and, most frequently, severe diarrhea that was only present in early-onset disease. In conclusion, we report the largest cohort of patients with FHL5 so far, describe an extended disease...

GENOTYPE-PHENOTYPE STUDY OF FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS TYPE 3

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Sieni , Elena; Cetica , Valentina; Santoro , Alessandra; Beutel , Karin; Mastrodicasa , Elena; Meeths , Marie; Ciambotti , Benedetta; Brugnolo , Francesca; Zur Stadt , Udo; Pende , Daniela; Moretta , Lorenzo; Griffiths , Gillian M.; Henter , Jan-Inge; Janka , Gritta; Arico , Maurizio

2011-01-01

Abstract Background: Mutations of UNC13D are causative for FHL3 (OMIM 608898). We present a genotype-phenotype study of 845 FHL3 patients. Methods: A consortium of 3 countries planned to pool in a common database data on presenting features and mutations from individual patients with biallelic UNC13D mutations. Results: 845 FHL3 patients (median age: 4.1 months) were reported from Florence, Italy (n=54), Hamburg, Germany (n=18), Stockholm, Sweden (n=123). Their ethnic origi...

Contribution to diagnosis and treatment of bone marrow aspirate results in critically ill patients undergoing bone marrow aspiration: a retrospective study of 193 consecutive patients.

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Calvet, Laure; Pereira, Bruno; Sapin, Anne-Françoise; Mareynat, Gabrielle; Lautrette, Alexandre; Souweine, Bertrand

2017-01-01

The purpose of the work was to assess the contribution to diagnosis and/or treatment (CDT) of bone marrow aspiration (BMA) in the critically ill patient. The retrospective study included 193 patients. On the basis of BMA findings, contribution to diagnosis was defined by one of four previously unestablished diagnoses (maturation arrest of granulocyte precursors, hemophagocytic lymphohistiocytosis, hematological malignancy, marrow infiltration with cancer cells) and to treatment as the initiation or withdrawal of a specific treatment including the decision to forgo life-sustaining treatment (DFLST). A CDT of BMA was observed in 40/193 patients (20.7%). BMA contributed to diagnosis in 37 cases (granulocyte precursor maturation arrest, N  = 10; hemophagocytic lymphohistiocytosis, N  = 12; hematological malignancy, N  = 15) and to treatment in 14, including three DFLSTs. In multivariate analysis, the factors associated with a CDT were hematological malignancy, cancer or non-malignant hematological abnormality known on admission, indication for BMA excluding isolated thrombocytopenia, higher pre-BMA HScore (calculated prior to BMA), and higher SOFA score with or without platelet-count SOFA subscore. In the 160 patients without hematological malignancy or cancer known on admission, non-malignant hematological abnormality known on admission, indication for BMA excluding isolated thrombocytopenia, higher pre-BMA HScore, and higher SOFA score calculated with or without platelet-count SOFA subscore were independently associated with a CDT of BMA. BMA can have a significant CDT in ICU patients with or without a known hematological malignancy or cancer on admission. An HScore calculated before BMA can be a valuable tool for predicting a CDT of BMA.

Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

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Larroche, C; Scieux, C; Honderlick, P; Piette, A M; Morinet, F; Blétry, O

2002-10-01

Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

CLINICAL CASE OF TOCILIZUMAB THERAPY IN A PATIENT WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

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E. I. Alexeeva

2013-01-01

Full Text Available The article presents a case of successful application of a monoclonal antibodies drug to interleukin 6 receptors (tocilizumab at severe systemic juvenile idiopathic arthritis with the development of secondary hemophagocytic syndrome. Tocilizumab treatment secured a decrease in clinical and laboratory parameters of the disease activity, life quality improvement, systemic juvenile idiopathic arthritis and hemophagocytic syndrome remission and allowed avoiding the per os prescription of glucocorticoids.

Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy

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R Rajyalakshmi

2016-01-01

Full Text Available Griscelli syndrome (GS is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, RAB27A (GS2, and MLPH (GS3 genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.

How genetic testing can lead to targeted management of XIAP deficiency-related inflammatory bowel disease

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Nielsen, Ole Haagen; LaCasse, Eric Charles

2017-01-01

infections, such as Epstein-Barr virus (EBV). Children with XIAP-related XLP-2 may present with either familial hemophagocytic lymphohistiocytosis, often triggered in response to EBV infection, or with a treatment-refractory severe pediatric form of inflammatory bowel disease (IBD) that might be diagnosed...... treatment history and patient morbidity/mortality since its original identification in 2006. Since XLP-2 is rare, cases are probably undergiagnosed or misdiagnosed. Consideration of XLP-2 in children with severe symptoms of IBD can prevent serious morbidities and mortality, avoid unnecessary procedures......, and expedite specific targeted therapy.Genet Med advance online publication 14 July 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.82....

A web-based delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients.

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Hejblum, Gilles; Lambotte, Olivier; Galicier, Lionel; Coppo, Paul; Marzac, Christophe; Aumont, Cédric; Fardet, Laurence

2014-01-01

The diagnosis of the reactive form of hemophagocytic syndrome in adults remains particularly difficult since none of the clinical or laboratory manifestations are specific. We undertook a study in order to elicit which features constitute helpful criteria for a positive diagnosis. In this Delphi study, the features investigated in the questionnaire and the experts invited to participate in the survey were issued from a bibliographic search. The questionnaire was iteratively proposed to experts via a web-based application with a feedback of the results observed at the preceding Delphi round. Experts were asked to label each investigated criterion in one of the following categories: absolutely required, important, of minor interest, or not assessable in the routine practice environment. A positive consensus was a priori defined as at least 75% answers observed in the categories absolutely required and important. The questionnaire investigated 26 criteria and 24 experts originating from 13 countries participated in the second and final Delphi round. A positive consensus was reached for the nine following criteria: unilineage cytopenia, bicytopenia, pancytopenia, presence of hemophagocytosis pictures on a bone marrow aspirate or on a tissue biopsy, high ferritin level, fever, organomegaly, presence of a predisposing underlying disease, and high level of lactate dehydrogenase. A negative consensus was reached for 13 criteria, and an absence of consensus was observed for 4 criteria. The study constitutes the first initiative to date for defining international guidelines devoted to the positive diagnosis of the reactive form of hemophagocytic syndrome.

Secondary Hemophagocytic Syndrome Associated with Richter’s Transformation in Chronic Lymphocytic Leukemia

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Nura El-Haj

2014-01-01

Full Text Available Hemophagocytic syndrome (HPS is an extremely rare condition arising from the overactivation of one’s own immune system. It results in excessive inflammation and tissue destruction. Prompt initiation of treatment is warranted in either scenario in order to decrease mortality. Most cases are triggered by infectious agents, malignancy, or drugs. We describe the first case of a CLL patient presenting with HPS due to acquisition of EBV-related large cell lymphoma in the setting of profound immunodeficiency.

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

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Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

2017-02-22

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder.

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Ogier de Baulny, Hélène; Schiff, Manuel; Dionisi-Vici, Carlo

2012-05-01

Lysinuric protein intolerance (LPI) is an inherited defect of cationic amino acid (lysine, arginine and ornithine) transport at the basolateral membrane of intestinal and renal tubular cells caused by mutations in SLC7A7 encoding the y(+)LAT1 protein. LPI has long been considered a relatively benign urea cycle disease, when appropriately treated with low-protein diet and l-citrulline supplementation. However, the severe clinical course of this disorder suggests that LPI should be regarded as a severe multisystem disease with uncertain outcome. Specifically, immune dysfunction potentially attributable to nitric oxide (NO) overproduction secondary to arginine intracellular trapping (due to defective efflux from the cell) might be a crucial pathophysiological route explaining many of LPI complications. The latter comprise severe lung disease with pulmonary alveolar proteinosis, renal disease, hemophagocytic lymphohistiocytosis with subsequent activation of macrophages, various auto-immune disorders and an incompletely characterized immune deficiency. These results have several therapeutic implications, among which lowering the l-citrulline dosage may be crucial, as excessive citrulline may worsen intracellular arginine accumulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Epstein-Barr virus-induced infectious mononucleosis after two separate episodes of virus-associated hemophagocytic syndrome.

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Ohno, Tatsuharu; Ueda, Yo; Kishimoto, Wataru; Arimoto-Miyamoto, Kazue; Takeoka, Tomoharu; Tsuji, Masaaki

2009-01-01

A 24-year-old man, who had suffered previous two episodes of non- Epstein-Barr virus (EBV)-associated hemophagocytic syndrome (HPS) at the ages of 16 and 18, developed EBV-induced infectious mononucleosis. His antibody pattern to EBV highlighted the initial infection. The disease took a self-limited course without developing into HPS. No reactivation of EBV infection was noted over the following 6 years. The patient may have attained immune competency in adulthood, which was somehow impaired during his adolescence.

Genotype–phenotype study of familial haemophagocytic lymphohistiocytosis type 3

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Sieni, Elena; Cetica, Valentina; Santoro, Alessandra; Beutel, Karin; Mastrodicasa, Elena; Meeths, Marie; Ciambotti, Benedetta; Brugnolo, Francesca; zur Stadt, Udo; Pende, Daniela; Moretta, Lorenzo; Griffiths, Gillian M; Henter, Jan-Inge; Janka, Gritta; Aricò, Maurizio

2014-01-01

Background Mutations of UNC13D are causative for familial haemophagocytic lymphohistiocytosis type 3 (FHL3; OMIM 608898). Objective To carry out a genotype–phenotype study of patients with FHL3. Methods A consortium of three countries pooled data on presenting features and mutations from individual patients with biallelic UNC13D mutations in a common database. Results 84 patients with FHL3 (median age 4.1 months) were reported from Florence, Italy (n=54), Hamburg, Germany (n=18), Stockholm, Sweden (n=12). Their ethnic origin was Caucasian (n=57), Turkish (n=10), Asian (n=7), Hispanic (n=4), African (n=3) (not reported (n=3)). Thrombocytopenia was present in 94%, splenomegaly in 96%, fever in 89%. The central nervous system (CNS) was involved in 49/81 (60%) patients versus 36% in patients with FHL2 (p=0.001). A combination of fever, splenomegaly, thrombocytopenia and hyperferritinaemia was present in 71%. CD107a expression, NK activity and Munc 13-4 protein expression were absent or reduced in all but one of the evaluated patients. 54 different mutations were observed, including 15 new ones: 19 missense, 14 deletions or insertions, 12 nonsense, nine splice errors. None was specific for ethnic groups. Patients with two disruptive mutations were younger than patients with two missense mutations (p<0.001), but older than comparable patients with FHL2 (p=0.001). Conclusion UNC13D mutations are scattered over the gene. Ethnic-specific mutations were not identified. CNS involvement is more common than in FHL2; in patients with FHL3 and disruptive mutations, age at diagnosis is significantly higher than in FHL2. The combination of fever, splenomegaly, thrombocytopenia and hyperferritinaemia appears to be the most easily and frequently recognised clinical pattern and their association with defective granule release assay may herald FHL3. PMID:21248318

Novel Munc13–4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis

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Santoro, A; Cannella, S; Bossi, G; Gallo, F; Trizzino, A; Pende, D; Dieli, F; Bruno, G; Stinchcombe, J C; Micalizzi, C; De Fusco, C; Danesino, C; Moretta, L; Notarangelo, L D; Griffiths, G M; Aricò, M

2006-01-01

Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem‐cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13–4 gene have recently been described in patients with FHL. We sequenced the Munc13–4 gene in all patients with haemophagocytic lymphohistiocytosis not due to PRF1 mutations. In 15 of the 30 families studied, 12 novel and 4 known Munc13–4 mutations were found, spread throughout the gene. Among novel mutations, 2650C→T introduced a stop codon; 441del A, 532del C, 3082del C and 3226ins G caused a frameshift, and seven were mis sense mutations. Median age of diagnosis was 4 months, but six patients developed the disease after 5 years of age and one as a young adult of 18 years. Involvement of central nervous system was present in 9 of 15 patients, activity of natural killer cells was markedly reduced or absent in 13 of 13 tested patients. Chemo‐immunotherapy was effective in all patients. Munc13–4 mutations were found in 15 of 30 patients with FHL without PRF1 mutations. Because these patients may develop the disease during adolescence or even later, haematologists should include FHL2 and FHL3 in the differential diagnosis of young adults with fever, cytopenia, splenomegaly and hypercytokinaemia. PMID:16825436

Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism.

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Dotta, Laura; Parolini, Silvia; Prandini, Alberto; Tabellini, Giovanna; Antolini, Maddalena; Kingsmore, Stephen F; Badolato, Raffaele

2013-10-17

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic

Typhoid fever causing haemophagocytic lymphohistiocytosis in a non-endemic country - first case report and review of the current literature.

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Sánchez-Moreno, Paula; Olbrich, Peter; Falcón-Neyra, Lola; Lucena, Jose Manuel; Aznar, Javier; Neth, Olaf

2018-06-07

Development of secondary haemophagocytic lymphohistiocytosis (sHLH) in the context of typhoid fever (TF) is a very rare but serious complication. Description of the first pediatric case of typhoid fever acquired in a non-endemic area complicated by sHLH. A systematic literature review of sHLH in the context of TF was performed with extraction of epidemiological, clinical and laboratory data. The literature search revealed 17 articles (22 patients). Fifteen patients were eligible for data analysis (53.4% children). All patients had fever and pancytopenia. Transaminases and LDH were frequently elevated (46.6%). Salmonella typhi was detected mainly by blood culture (64.3%). All the patients received antibiotics whereas immunomodulation (dexamethasone) was used in two cases. A high suspicion index for this condition is needed even in non-endemic areas. The addition of immunmodulation to standard antimicrobial therapy should be considered in selected cases. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Post-hematopoietic stem cell transplant hemophagocytic lymphohistiocytosis or an impostor: Case report and review of literature.

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Vatsayan, Anant; Pateva, Irina; Cabral, Linda; Dalal, Jignesh; Abu-Arja, Rolla

2018-03-25

HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment syndrome, graft rejection/failure, acute graft-vs-host disease, infections systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy). Moreover, this period is usually marked by febrile illness, cytopenia, and a "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin and sCD25. These parameters overlap with the diagnostic criteria for HLH. Such confounding factors make the management of post-HSCT HLH quite challenging. We illustrate this critical issue with case report of a patient who was diagnosed with HLH after allogeneic HSCT for tAML. He received MP and CsA for HLH but VP-16 was not administered due to fear of severe myelosuppression. Fortunately, he responded well to treatment and remains in remission to date. We recommend caution while using HLH-94/HLH-2004 guidelines for the diagnosis and management of post-HSCT HLH. In this article, we pinpoint these issues with a brief review of all the pediatric cases and clinical studies of post-HSCT HLH along with a critical evaluation of its various diagnostic criteria. Finally, based on the limitations of current diagnostic criteria, we suggest a need for formulating disease-specific diagnostic criteria for post-HSCT HLH. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pregnancy-related hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection: A diagnostic and therapeutic challenge

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Nor Rafeah Tumian

2015-08-01

Conclusion: This case highlights the challenges and difficulties involved in the diagnosis and management of pregnancy-related HLH. Immunosuppressive treatment for HLH can precipitate life-threatening opportunistic infections, which need to be promptly diagnosed and treated.

Leishmania infantum and Epstein-Barr virus co-infection in a patient with hemophagocytosis

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Zied Gaifer

2017-01-01

Full Text Available The authors describe a rare case of a 27-year old previously healthy male presenting with high grade fever, pancytopenia, hepatosplenomegaly, high levels of ferritin and triglyceride, suggesting a diagnosis of hemophagocytic lymphohistiocytosis (HLH syndrome. Other investigations showed a positive Leishmania infantum serology and high Epstein-Barr virus (EBV viremia. The diagnosis of a visceral leishmaniasis was confirmed by bone morrow biopsy, which showed Leishman-Donovan bodies and evidence of HLH. The patient received liposomal amphotericin B and he had a complete resolution of his symptoms and clearance of EBV viremia. This case of HLH associated with visceral leishmaniasis and EBV co-infection raises the question about the significance of EBV in patients with HLH. The treatment of actual etiological agent can lead to complete cure while using current recommend chemotherapy for HLH-related EBV in a patient with hidden infection may have deleterious effects.

Clinicopathological categorization of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease: an analysis of 42 cases with an emphasis on prognostic implications.

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Paik, Jin Ho; Choe, Ji-Young; Kim, Hyojin; Lee, Jeong-Ok; Kang, Hyoung Jin; Shin, Hee Young; Lee, Dong Soon; Heo, Dae Seog; Kim, Chul-Woo; Cho, Kwang-Hyun; Kim, Tae Min; Jeon, Yoon Kyung

2017-01-01

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1.8) were predominant. Clinicopathologically, three systemic and one cutaneous category were developed: hemophagocytic lymphohistiocytosis (HLH; 26% [11/42]), chronic active EBV infection (CAEBV; 31% [13/42]), systemic unclassifiable disease (24% [10/42]), and hydroa vacciniforme/hydroa vacciniforme-like lymphoma (HV/HVL; 19% [8/42]). Prognostically, cutaneous disease (HV/HVL) was better than systemic disease (p = 0.014; median, 285 vs. 10 months). In systemic diseases, HLH was worst (p = 0.002; 3[HLH] vs. 4[unclassifiable] vs. not reached [CAEBV]). Univariate survival analysis (n = 42) revealed cytopenia (≥one lineage; p 40 years; p = 0.001), T-cell lineage (p = 0.041), hemophagocytic histiocytes (p = 0.031), elevated lactate dehydrogenase (p = 0.020), and liver dysfunction (p = 0.023) predicted shorter survival. In multivariate analysis, T-cell lineage (p = 0.025 [HR =11.3]) and cytopenia (p = 0.028 [HR =5.4]) were independent prognostic factors. Therefore, EBV-T/NK-LPD could be classified into four prognostic categories.

Neuroimaging of nonaccidental head trauma: pitfalls and controversies

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Fernando, Sujan [University of Missouri-Kansas School of Medicine, Department of Medicine, Kansas City, MO (United States); Obaldo, Ruby E. [The University of Kansas Medical Center, Department of Radiology, Kansas City, MO (United States); Walsh, Irene R. [The University of Missouri-Kansas City, Children' s Mercy Hospitals and Clinics, Department of Emergency Medicine, Kansas City, MO (United States); Lowe, Lisa H. [The University of Missouri-Kansas City, Children' s Mercy Hospitals and Clinics, Department of Radiology, Kansas City, MO (United States)

2008-08-15

Although certain neuroimaging appearances are highly suggestive of abuse, radiological findings are often nonspecific. The objective of this review is to discuss pitfalls, controversies, and mimics occurring in neuroimaging of nonaccidental head trauma in order to allow the reader to establish an increased level of comfort in distinguishing between nonaccidental and accidental head trauma. Specific topics discussed include risk factors, general biomechanics and imaging strategies in nonaccidental head trauma, followed by the characteristics of skull fractures, normal prominent tentorium and falx versus subdural hematoma, birth trauma versus nonaccidental head trauma, hyperacute versus acute on chronic subdural hematomas, expanded subarachnoid space versus subdural hemorrhage, controversy regarding subdural hematomas associated with benign enlarged subarachnoid spaces, controversy regarding hypoxia as a cause of subdural hematoma and/or retinal hemorrhages without trauma, controversy regarding the significance of retinal hemorrhages related to nonaccidental head trauma, controversy regarding the significance of subdural hematomas in general, and pitfalls of glutaric aciduria type 1 and hemophagocytic lymphohistiocytosis mimicking nonaccidental head trauma. (orig.)

Neuroimaging of nonaccidental head trauma: pitfalls and controversies

International Nuclear Information System (INIS)

Fernando, Sujan; Obaldo, Ruby E.; Walsh, Irene R.; Lowe, Lisa H.

2008-01-01

Although certain neuroimaging appearances are highly suggestive of abuse, radiological findings are often nonspecific. The objective of this review is to discuss pitfalls, controversies, and mimics occurring in neuroimaging of nonaccidental head trauma in order to allow the reader to establish an increased level of comfort in distinguishing between nonaccidental and accidental head trauma. Specific topics discussed include risk factors, general biomechanics and imaging strategies in nonaccidental head trauma, followed by the characteristics of skull fractures, normal prominent tentorium and falx versus subdural hematoma, birth trauma versus nonaccidental head trauma, hyperacute versus acute on chronic subdural hematomas, expanded subarachnoid space versus subdural hemorrhage, controversy regarding subdural hematomas associated with benign enlarged subarachnoid spaces, controversy regarding hypoxia as a cause of subdural hematoma and/or retinal hemorrhages without trauma, controversy regarding the significance of retinal hemorrhages related to nonaccidental head trauma, controversy regarding the significance of subdural hematomas in general, and pitfalls of glutaric aciduria type 1 and hemophagocytic lymphohistiocytosis mimicking nonaccidental head trauma. (orig.)

Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

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Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-05-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.

Two Novel Mutations Identified in an African-American Child with Chediak-Higashi Syndrome

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Kerry Morrone

2010-01-01

Full Text Available Background. Chediak-Higashi syndrome (CHS is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an “accelerated phase” characterized by hemophagocytic lymphohistiocytosis (HLH. The disease is caused by mutations in the CHS1/LYST gene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in the CHS1 gene: c.3622C>T (p.Q1208X and c.11002G>T (p.E3668X. Conclusions. Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in the CHS1 gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS.

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey

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Alişan Yıldıran

2017-12-01

Full Text Available Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11, Chediak-Higashi syndrome (n=2, leukocyte adhesion deficiency (n=2, MHC class 2 deficiency (n=2, chronic granulomatous syndrome (n=2, hemophagocytic lymphohistiocytosis (n=1, Wiskott-Aldrich syndrome (n=1, and Omenn syndrome (n=1. Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey.

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Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül

2017-12-01

Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

Las histiocitosis Histiocytosis

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Eva Svarch

2001-12-01

disease. Treatment depends on the spread of the process. An only lesion tends to spontaneously disappear. Also diagnostic biopsy with or without steroid injection may lead to healing. Those patients with multisystem disease may benefit from an steroid and cytostatic-based treatment or even from progenitor hematopoietic cell transplantation. Sinus histiocytosis with massive lymphadenopathies or Rosai Dorfman disease is a benign and usually self-limited disease which is caused by the macrophage proliferation; it generally affects children and young adults. Hemophagocytic lymphohistiocytosis is also caused by macrophage proliferation and is a rare disease with a high mortality rate. It can be familiar hemophagocytic lymphohistiocytosis (recessive autosomal or secondary to viral infections, being the latter form the most frequent in infants. At present, mainly in the familiar variant, the progenitor hematopoietic allogenic transplant may serve as the only curative option

Characterisation of successive Acinetobacter baumannii isolates from a deceased haemophagocytic lymphohistiocytosis patient.

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Choi, Hyeon Jin; Kil, Min Cheol; Choi, Ji-Young; Kim, Sun Ju; Park, Ki-Sup; Kim, Yae-Jean; Ko, Kwan Soo

2017-01-01

In this study, 38 Acinetobacter baumannii isolates successively isolated from blood, skin swabs and tracheal aspirates from a single patient who died from haemophagocytic lymphohistiocytosis were investigated. The isolates were collected between March 2012 and August 2012. A. baumannii genotypes were determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In vitro antimicrobial susceptibility testing was performed and colistin heteroresistance and persistence were evaluated. The structure of AbaR resistance islands was explored, and serum sensitivity was determined. Based on MLST analysis, all 38 A. baumannii isolates showed the same sequence type (ST138). However, PFGE analysis showed that isolates from blood samples belonged to different genotypes depending on the isolation time: whilst blood isolates obtained at the early stages showed restriction patterns similar to those of isolates from other sources, isolates obtained at later stages exhibited a distinct pattern. All isolates were resistant to imipenem, cefepime, ciprofloxacin and piperacillin/tazobactam. Five isolates from tracheal aspirates and one from a skin swab were resistant to polymyxins, and two isolates from skin swabs and one from another source were non-susceptible to tigecycline. All colistin-susceptible isolates showed heteroresistance to colistin, and four were persisters. Isolates from blood showed higher survival rates against human serum than those from other sources. This study shows that the patient was infected with more than one A. baumannii strain. Heteroresistance, persistence or evasion of the innate immune response may explain the failure of antimicrobial treatments in this patient. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function

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Snehal Shabrish

2016-01-01

Full Text Available Natural killer (NK cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA and calcium ionophore (Ca2+-ionophore instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p<0.0001. It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells.

X-Linked Lymphoproliferative Syndrome and Common Variable Immunodeficiency May Not Be Differentiated by SH2D1A and XIAP/BIRC4 Genes Sequence Analysis

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Nesrin Gulez

2011-01-01

Full Text Available The X-linked lymphoproliferative syndrome (XLP is a rare, inherited immunodeficiency characterized by recurrent episodes of hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, and/or lymphomas. Recently, X-linked inhibitor of apoptosis (XIAP/BIRC4 gene defects, in families with XLP but without SH2D1A gene defects, has been defined. The distinction from primary immunodeficiencies with a defined genetic cause is mandatory. A six-year-old male patient was admitted with the complaints of persistent general lymphadenopathy, for two years had fever, bilateral cervical multiple microlymphadenopathy, hepatic/splenic enlargement with laboratory findings as decreased serum immunoglobulins, negative EBV VCA IgM (viral capsid antigen and anti-EBV EA (antibody to early D antigen, positive EBV VCA IgG (viral capsid antigen and EBV EBNA (antibody to nuclear antigen. SH2D1A gene analysis was negative. XIAP/BIRC4 sequencing revealed two novel single nucleotide variants (exon 7, 1978G > A, and 1996T > A in the 3′UTR of the gene in both patient and mother which were not disease causing. XIAP protein expression was found to be normal. The clinical and laboratory resemblance, no gene mutations, and normal XIAP protein expression led us to think that there may be another responsible gene for XLP. The patient will to be followed up as CVID until he presents new diagnostic signs or until the identification of a new gene.

Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

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Samantha K Dunmire

Full Text Available Epstein-Barr Virus (EBV causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza, respiratory syncytial virus (RSV, human rhinovirus (HRV, attenuated yellow fever virus (YFV, and Dengue fever virus (DENV, revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes

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Dunmire, Samantha K.; Odumade, Oludare A.; Porter, Jean L.; Reyes-Genere, Juan; Schmeling, David O.; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C.; Balfour, Henry H.; Hogquist, Kristin A.

2014-01-01

Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans. PMID:24465555

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

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Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

2013-01-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

DEFF Research Database (Denmark)

Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke

2010-01-01

Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

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Prencipe, Giusi; Caiello, Ivan; Pascarella, Antonia; Grom, Alexei A; Bracaglia, Claudia; Chatel, Laurence; Ferlin, Walter G; Marasco, Emiliano; Strippoli, Raffaele; de Min, Cristina; De Benedetti, Fabrizio

2018-04-01

The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68 + macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Molecular study of the perforin gene in familial hematological malignancies

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El Abed Rim

2011-09-01

Full Text Available Abstract Perforin gene (PRF1 mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81. Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein.

Characterization of variants in the promoter of BZLF1 gene of EBV in nonmalignant EBV-associated diseases in Chinese children

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Yang Shuang

2010-05-01

Full Text Available Abstract Background Diseases associated with Epstein-Barr virus (EBV infections, such as infectious mononucleosis (IM, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH and chronic active EBV infection (CAEBV are not rare in Chinese children. The association of type 1 or type 2 EBV and variants of the EBV BZLF1 promoter zone (Zp with these diseases is unclear. Results The objective of this study was to investigate the relationship between EBV genotypes (Zp variants and EBV type 1 and 2 and the clinical phenotypes of EBV-associated diseases in Chinese children. The Zp region was directly sequenced in 206 EBV-positive DNA samples from the blood of patients with IM, EBV-HLH, CAEBV, and healthy controls. Type 1 or type 2 EBV was examined by PCR for EBNA2 and EBNA3C subtypes. Four polymorphic Zp variants were identified: Zp-P, Zp-V3, Zp-P4 and Zp-V1, a new variant. The Zp-V3 variant was significantly associated with CAEBV (P ≤ 0.01. The frequency of co-infection with Zp variants was higher in patients with CAEBV and EBV-HLH, compared with IM and healthy controls, mostly as Zp-P+V3 co-infection. Type 1 EBV was predominant in all categories (81.3-95% and there was no significant difference in the frequency of the EBV types 1 and 2 in different categories (P > 0.05. Conclusions Type 1 EBV and BZLF1 Zp-P of EBV were the predominant genotypes in nonmalignant EBV associated diseases in Chinese children and Zp-V3 variant may correlates with the developing of severe EBV infection diseases, such as CAEBV and EBV-HLH.

Infantile Hemophagocytic Lymphohistiocytosis in a Case of Chediak-Higashi Syndrome Caused by a Mutation in the LYST/CHS1 Gene Presenting With Delayed Umbilical Cord Detachment and Diarrhea

DEFF Research Database (Denmark)

Nielsen, Christian; Agergaard, Charlotte N; Jakobsen, Marianne A

2015-01-01

A 2-month-old female infant, born to consanguineous parents, presented with infections in skin and upper respiratory tract. She was notable for delayed umbilical cord detachment, partial albinism, and neurological irritability. Giant granules were present in white blood cells. The intracellular...... in this severe phenotype of Chediak-Higashi syndrome was probably induced by rotaviral infection. Interestingly, the intracellular perforin content in CD8 T cells seems to correlate to the immune activation state of the patient. Late separation of the umbilical cord in concordance with clinical symptoms should...

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

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Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A

1996-09-01

For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and

Synergistic defects of novo FAS and homozygous UNC13D leading to autoimmune lymphoproliferative syndrome-like disease: A 10-year-old Chinese boy case report.

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Gu, Hao; Ma, Jie; Chen, Zhenping; Wang, Jing; Zhang, Rui; Wu, Runhui

2018-06-01

Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly and lymphadenopathy along with hemocytopenia. This case report describes a 10-year-old boy presenting with signs of autoimmune disease, splenomegaly, hepatomegaly and resistant hemocytopenia. Sirolimus controlled the relapsed thrombocytopenia after splenectomy. Sequencing of the FAS gene identified two spontaneous heterozygous mutations (c.234 T > G, p.D78E) (c.236dupA, p.P80Tfs*26). The boy's homozygous missense variation (c.2588G > A, p.G863D) (rs140184929) in UNC13D gene had been identified as being related to familial hemophagocytic lymphohistiocytosis (FHL). TCRαβ + CD4/CD8 double-negative T cells (markers of ALPS) were not significantly increased from the outset. Elevated cytokines, such as interferon (IFN)-γ, interleukin (IL)-6 and tumor necrosis factor α decreased to normal levels after splenectomy whereas IL-10 remained high. Immunological analysis of the patient revealed a marked depletion of forkhead-box P3 + expressing regulatory T cells (Treg) and Th17 cells. The obtained data demonstrate that mutations to FAS and UNC13D which result in overwhelming T-cell and macrophage activation, one associated with inhibited Treg cell development and a severe ALPS-like symptom. Therefore, we propose that variations of UND13D may be a risk factor of ALPS development. Copyright © 2017. Published by Elsevier B.V.

Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome.

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Hsieh, Wen-Chuan; Chang, Yao; Hsu, Mei-Chi; Lan, Bau-Shin; Hsiao, Guan-Chung; Chuang, Huai-Chia; Su, Ih-Jen

2007-05-01

Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.

Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study.

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Löfstedt, Alexandra; Chiang, Samuel C C; Onelöv, Erik; Bryceson, Yenan T; Meeths, Marie; Henter, Jan-Inge

2015-12-01

Mutations in genes for perforin-dependent lymphocyte cytotoxicity are associated with haemophagocytic lymphohistiocytosis, a rare disease of severe hyperinflammation that typically becomes evident in early childhood. It has been suggested that individuals with hypomorphic biallelic mutations in genes associated with haemophagocytic lymphohistiocytosis are at increased risk of developing haematological malignancies. We aimed to assess whether relatives of patients with primary haemophagocytic lymphohistiocytosis (ie, heterozygous carriers of these mutated genes) were more likely to develop cancer. In this retrospective cohort study, we used a multigeneration registry to identify relatives (parents and grandparents) of 79 Swedish children (Karolinska Institutet Research Foundation, Stockholm County Council (ALF-project). Copyright © 2015 Elsevier Ltd. All rights reserved.

Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

DEFF Research Database (Denmark)

Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke

2010-01-01

Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weaknes...

Missing cells: pathophysiology, diagnosis and management of (pancytopenia in childhood

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Miriam eErlacher

2015-07-01

Full Text Available Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia whereas antibody mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. In contrast, pancytopenia is frequently associated with a hypocellular bone marrow and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC can reliably be differentiated on a morphological level the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pancytopenia, their pathophysiology, characteristic bone marrow findings and therapeutic approaches.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

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Cohen, Jeffrey I; Dropulic, Lesia; Hsu, Amy P; Zerbe, Christa S; Krogmann, Tammy; Dowdell, Kennichi; Hornung, Ronald L; Lovell, Jana; Hardy, Nancy; Hickstein, Dennis; Cowen, Edward W; Calvo, Katherine R; Pittaluga, Stefania; Holland, Steven M

2016-07-01

Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease.

Science.gov (United States)

Aguayo-Hiraldo, Paibel; Arasaratnam, Reuben; Rouce, Rayne H

Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Late-Onset Non-HLH Presentations of Growth Arrest, Inflammatory Arachnoiditis, and Severe Infectious Mononucleosis, in Siblings with Hypomorphic Defects in UNC13D

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Paul Edgar Gray

2017-08-01

Full Text Available Bi-allelic null mutations affecting UNC13D, STXBP2, or STX11 result in defects of lymphocyte cytotoxic degranulation and commonly cause familial hemophagocytic lymphohistiocytosis (FHL in early life. Patients with partial loss of function are increasingly being diagnosed after presenting with alternative features of this disease, or with HLH later in life. Here, we studied two sisters with lymphocyte degranulation defects secondary to compound heterozygote missense variants in UNC13D. The older sibling presented aged 11 with linear growth arrest and delayed puberty, 2 years prior to developing transient ischemic attacks secondary to neuroinflammation and hypogammaglobulinemia, but no FHL symptoms. Her geno-identical younger sister was initially asymptomatic but then presented at the same age with severe EBV-driven infectious mononucleosis, which was treated aggressively and did not progress to HLH. The sisters had similar natural killer cell degranulation; however, while cytotoxic activity was moderately reduced in the asymptomatic patient, it was completely absent in both siblings during active disease. Following allogeneic bone marrow transplantation at the age of 15, the older child has completely recovered NK cell cytotoxicity, is asymptomatic, and has experienced an exceptional compensatory growth spurt. Her younger sister was also successfully transplanted and is currently disease free. The current study reveals previously unappreciated manifestations of FHL in patients who inherited hypomorphic gene variants and also raises the important question of whether a threshold of minimum NK function can be defined that should protect a patient from serious disease manifestations such as HLH.

Síndrome da ativação do macrófago em paciente com artrite idiopática juvenil poliarticular Macrophage activation syndrome in a patient with polyarticular juvenile idiopathic arthritis

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Acir Rachid

2004-10-01

Full Text Available A linfohistiocitose hemofagocítica caracteriza-se por ativação e proliferação excessiva de linfócitos e macrófagos. Quando associada à artrite idiopática juvenil é também conhecida por "síndrome de ativação do macrófago", sendo uma complicação potencialmente fatal desta doença. Apresentamos o caso de uma mulher de 26 anos portadora de artrite idiopática juvenil (poliartrite, fator reumatóide negativo, com diagnóstico aos 13 anos, em uso de antiinflamatórios não esteroidais (diclofenaco, nimesulide. Admitida com quadro de resposta inflamatória sistêmica, febre, linfonodomegalia, esplenomegalia, anemia, trombocitopenia, hipofibrinogenemia, hiperferritinemia, hipertrigliceridemia e achados de hematofagocitose na medula óssea. Os autores discutem aspectos relacionados com a patogênese, diagnóstico e tratamento desta doença pouco conhecida.Hemophagocytic lymphohistiocytosis is characterized by massive lymphocyte and macrophage activation and proliferation. When observed in association with juvenile idiopathic arthritis it is also called "macrophage activation syndrome" being a potentially lethal complication of this disease. We report the case of a 26 years old woman with juvenile idiopathic arthritis (polyarthritis, rheumatoid factor negative since 13 years old, receiving nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide. She was admitted with systemic inflammatory response, fever, lymph node enlargement, splenomegaly, anemia, thrombocytopenia, hypofibrinogenemia, hyperferritinemia, hypertriglyceridemia and bone marrow hemophagocytosis. Aspects related to pathogenesis, diagnosis and treatment of this little known disease are discussed.

Capillary leak syndrome: etiologies, pathophysiology, and management.

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Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai

2017-07-01

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

Science.gov (United States)

Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

2003-10-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious

A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

Science.gov (United States)

Sekiguchi, Yasunobu; Shimada, Asami; Imai, Hidenori; Wakabayashi, Mutsumi; Sugimoto, Keiji; Nakamura, Noriko; Sawada, Tomohiro; Komatsu, Norio; Noguchi, Masaaki

2014-01-01

The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study

Science.gov (United States)

Bergsten, Elisabet; Horne, AnnaCarin; Aricó, Maurizio; Astigarraga, Itziar; Egeler, R. Maarten; Filipovich, Alexandra H.; Ishii, Eiichi; Janka, Gritta; Ladisch, Stephan; Lehmberg, Kai; McClain, Kenneth L.; Minkov, Milen; Montgomery, Scott; Nanduri, Vasanta; Rosso, Diego

2017-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P = .020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly. PMID:28935695

Reactive hemophagocytic syndromes in children with rheumatic diseases

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Piotr Gietka

2011-04-01

Full Text Available Reactive haemophagocytic syndrome (RHPS, also calledmacrophage activation syndrome (MAS, is a serious complicationof viral, rheumatic and malignant diseases, thought to be causedby the excessive activation of T lymphocytes and macrophages.MAS is characterized by polyorgan involvement with typical features:non-remitting fever, hepatic enlargement, considerable loweringof blood cell count and erythrocyte sedimentation rate (ESR,elevation of serum glutamic-oxaloacetic transaminase (SGOT,serum glutamic pyruvic transaminase (SGPT, lactate dehydrogenase(LDH and serum ferritin level, with hypofibrinogenemia. Themost characteristic feature is the presence of well differentiatedmacrophages, revealing an active haemophagocytosis in the bonemarrow aspirate. Because of rapid progression and fatal prognosisof the disease, prompt and immediate therapeutic intervention isvery important. Although there is no standardized treatment, commonlyapplied glucocorticoids (GCS, and cyclosporine A (CsA areused. The study was aimed to a general characteristics of pathogenicfactors, clinical picture, laboratory features and results oftreatment in 8 children with RHPS /MAS. Material and methods: The study included 8 children (5 girls and3 boys aged 3 to 16 years (mean age was 10 years and 3 monthshospitalized in the Clinic of Pediatrics at IPCZD and in the Departmentof Pediatric Rheumatology at the Institute of Rheumatology in Warsaw. The analysis covered potential etiological factors, consideringthe basic disease, clinical symptoms (Table II, results oflaboratory tests (Table III, including immunological tests, appliedtherapy. In 4 patients, systemic-onset juvenile idiopathic arthritiswas accompanied by MAS, and in 2 patients it was the first manifestationof sJIA. In one patient, EBV infection was confirmed bythe polymerase chain reaction (case 1. In patient 3, PCR evaluationrevealed Cytomegalovirus (CMV infection. Cytomegalovirus infectionwas also confirmed in case 4

Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A

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Ren'an Chen

2010-11-01

Full Text Available A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.

Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases.

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Parvaneh, Nima; Filipovich, Alexandra H; Borkhardt, Arndt

2013-09-01

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, maintains lifelong subclinical persistent infections in humans. In the circulation, EBV primarily infects the B cells, and protective immunity is mediated by EBV-specific cytotoxic T cells (CTLs) and natural killer (NK) cells. However, EBV has been linked to several devastating diseases, such as haemophagocytic lymphohistiocytosis (HLH) and lymphoproliferative diseases in the immunocompromised host. Some types of primary immunodeficiencies (PIDs) are characterized by the development of EBV-associated complications as their predominant clinical feature. The study of such genetic diseases presents an ideal opportunity for a better understanding of the biology of the immune responses against EBV. Here, we summarize the range of PIDs that are predisposed to EBV-associated haematological diseases, describing their clinical picture and pathogenetic mechanisms. © 2013 John Wiley & Sons Ltd.

SAMJ 8615.indd

African Journals Online (AJOL)

Autoimmune hepatitis. Haemophagocytic lymphohistiocytosis. Neonatal haemochromatosis. Autoimmune haemolytic anaemia with giant cell hepatitis. Toxic. Drugs/toxins/herbals. Amanita phalloides. Vascular. BuddChiari syndrome. Venoocclusive disease. Ischaemic hepatitis/shock liver. Post cardiac surgery. Liver trauma.

Fluorescence in situ hybridization is superior for monitoring Epstein Barr viral load in infectious mononucleosis patients.

Science.gov (United States)

Cao, Pengfei; Zhang, Meili; Wang, Wei; Dai, Yafei; Sai, Buqing; Sun, Jun; Wang, Lujuan; Wang, Fan; Li, Guiyuan; Xiang, Juanjuan

2017-05-03

Epstein Barr virus (EBV) plays a causal role in some diseases, including infectious mononucleosis, lymphoproliferative diseases and nasopharyngeal carcinoma. Detection of EBV infection has been shown to be a useful tool for diagnosing EBV-related diseases. In the present study, we compared the performance of molecular tests, including fluorescence in situ hybridization (FISH) and EBV real-time PCR, to those of serological assays for the detection of EBV infection. Thirty-eight patients with infectious mononucleosis (IM) were enrolled, of whom 31 were diagnosed with a mild type, and seven were diagnosed with IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection. Twenty healthy controls were involved in the study. The atypical lymphocytes in peripheral blood were detected under a microscope and the percentage of positive cells was calculated. EBV DNA load in peripheral blood was detected using real-time PCR. The FISH assay was developed to detect the EBV genome from peripheral blood mononuclear cells (PBMC). Other diagnosis methods including the heterophil agglutination (HA) test and EBV-VCA-IgM test, to detect EBV were also compared. SPSS17.0 was used for statistical analysis. In all, 5-41% atypical lymphocytes were found among the PBMC in mild IM patients, whereas 8-51% atypical lymphocytes were found in IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. There was no significant difference in the ratios of atypical lymphoma between patients of the different types. We observed that 71.2% of mild IM patients and 85.7% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients were positive for EBV-VCA-IgM. EBV-VCA-IgM was negative in all healthy control subjects. In addition, 67.1% of mild IM patients tested heterophile antibody positive, whereas 71.4% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection tested positive. EBV

Haemophagocytic lymphohistiocytosis: A fulminant syndrome ...

African Journals Online (AJOL)

ability of CTLs and NK cells to induce apoptosis of antigen- presenting cells and ... referred for stem cell transplantation.[8]. Much of our ... Five patients in whom acquired HLH was diagnosed, following bone marrow investigations .... Cases 1 and 2 were diagnosed with diffuse large B-cell lymphoma at the time of HLH ...

Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

DEFF Research Database (Denmark)

Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

2012-01-01

We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activatio...

Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

DEFF Research Database (Denmark)

Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

2012-01-01

We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activation...

Fatal tick-borne encephalitis in an immunosuppressed 12-year-old patient

Czech Academy of Sciences Publication Activity Database

Chmelík, V.; Chrdle, A.; Růžek, Daniel

2016-01-01

Roč. 74, 1 January (2016), s. 73-74 ISSN 1386-6532 R&D Projects: GA ČR GAP502/11/2116 Institutional support: RVO:60077344 Keywords : Tick-borne encephalitis * immunosuppressed patient * fatal case * haemophagocytic lymphohistiocytosis Subject RIV: EE - Microbiology, Virology Impact factor: 3.051, year: 2016

Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

Science.gov (United States)

2018-04-19

Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy

Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

DEFF Research Database (Denmark)

Yenson, P.R.; Forrest, D.; Schmiegelow, K.

2008-01-01

risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow...

Familial haemophagocytic lymphohistiocytosis: rare cause of acute ...

African Journals Online (AJOL)

Arun Kumar Agnihotri

prolonged fever, cytopenias, and hepatosplenomegaly. We describe a .... a), interleukin (IL), interferon alpha (INF-a), giving rise to the ... The diagnosis HLH can be established if one of either 1 or 2 below of the following criteria are fulfilled: 1.

Unusual cause of cholestatic jaundice in a patient with AIDS.

Science.gov (United States)

Kim, Su Bin; Shrivastava, Makardhwaj Sarvadaman; Anampa, Jesus M; Strakhan, Marianna

2013-08-23

A 61-year-old man with AIDS on chronic highly active antiretroviral treatment (HAART) presented with lethargy and jaundice and was found to have abnormal liver function tests (LFTs). Investigations including viral/autoimmune markers and imaging were unrevealing, except for positive Epstein-Barr virus. HAART was held, however, transaminases and total bilirubin continued to rise. The liver biopsy revealed classical Hodgkin's lymphoma (HL). HL presenting only with liver findings without lymphadenopathy is rare. Extreme cases can lead to fulminant liver failure. The bone marrow biopsy and dramatic elevation in serum ferritin were consistent with haemophagocytic lymphohistiocytosis. Finding a chemotherapy regimen was challenging given abnormal LFTs and HAART interactions. Initial chemotherapy regimen has successfully decreased LFTs; however, it was limited by pancytopenia. The patient's regimen was changed, however second regimen was complicated by neuropathy. LFTs improved and the patient was able to receive the standard care chemotherapy for HL with significant clinical, laboratory and radiological improvement.

Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome

DEFF Research Database (Denmark)

Schaer, Dominik J; Schleiffenbaum, Boris; Kurrer, Michael

2005-01-01

.1 mg/L), acute mononucleosis (median 8.2 mg/L), Leishmania infection (median 6.7 mg/L) and healthy controls (median 1.8 mg/L). Follow-up of patients with a relapsing course of the disease revealed close correlations of sCD163 with clinical disease activity, serum ferritin and other markers...

Advances in understanding the pathogenesis of HLH.

Science.gov (United States)

Usmani, G Naheed; Woda, Bruce A; Newburger, Peter E

2013-06-01

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi-organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined. © 2013 John Wiley & Sons Ltd.

Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

DEFF Research Database (Denmark)

Krabbe, Simon; Gül, Cigdem; Andersen, Bjarne

2016-01-01

elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic...... lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations....

XIAP Deficiency and MEFV Variants Resulting in Severe Manifestations – A Case Report

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Christiansen, Mette

2016-01-01

Background Heterozygous dominant or homozygous recessive MEFV mutations result in recurrent fever and abdominal pain, while XIAP deficiency is characterized by a high susceptibility to develop haemophagocytic lymphohistiocytosis triggered by EBV infection, recurrent splenomegaly and inflammatory...... Genetic testing identified variants in the MEFV gene (c.1223G>A; p.R408Q) indicating Familial Mediterranean Fever. Importantly, a hemizygous mutation in the X-linked inhibitor of apoptosis (XIAP)-gene (c.1026delT; I342fs) resulting in a frameshift was identified by whole exome sequencing in the patient...

Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis-associated skin ulcers on the face and surrounding a tracheotomy stoma.

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Nagamoto, Eiko; Fujisawa, Akihiko; Yoshino, Yuichiro; Yoshitsugu, Kanako; Odo, Masashi; Watanabe, Hidetaka; Igata, Toshikatsu; Noguchi, Hiromitsu

2014-01-01

A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

Fine-needle aspiration study of cystic papillary thyroid carcinoma: Rare cytological findings

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Maral Mokhtari

2016-01-01

Full Text Available Background: Cystic papillary thyroid carcinoma (CPTC is a variant of papillary carcinoma that has many mimickers in cytological grounds. Aim: To study the cytomorphologic features of CPTC and compare them to those of other cystic thyroid lesions using fine-needle aspiration cytology (FNAC. We also aimed to identify the cytomorphologic features that distinguish CPTC from other cystic thyroid lesions. Materials and Methods: Seventy-three cases of CPTC were included in the study. The cytomorphologic features of these cases were analyzed. The FNA smears of other thyroid lesions with cystic changes (300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasm were also studied. Results: The smears in CPTC revealed isolated follicular cells, small groups of cells with scalloped margins, cell swirls, small clusters with a cartwheel pattern, papillary clusters, intranuclear inclusions, nuclear grooves, sticky colloid, intracellular colloids, psammoma bodies, multinucleated giant cells, and foamy and hemosiderin laden macrophages. Small groups of cells with scalloped borders, cellular swirls, and small clusters with a cartwheel pattern were seen in CPTC, but not in other cystic lesions. Interestingly, mesothelial-like cells and hemophagocytic cells were seen in five and three cases of CPTC, respectively, but not in other cystic lesions. Conclusion: Mesothelial-like cells and hemophagocytic cells were observed in five and three cases of CPTC, respectively. Similar finding have not been previously reported in the literature.

Fine-needle aspiration study of cystic papillary thyroid carcinoma: Rare cytological findings

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Mokhtari, Maral; Kumar, Perikala Vijayananda; Hayati, Kamran

2016-01-01

Background: Cystic papillary thyroid carcinoma (CPTC) is a variant of papillary carcinoma that has many mimickers in cytological grounds. Aim: To study the cytomorphologic features of CPTC and compare them to those of other cystic thyroid lesions using fine-needle aspiration cytology (FNAC). We also aimed to identify the cytomorphologic features that distinguish CPTC from other cystic thyroid lesions. Materials and Methods: Seventy-three cases of CPTC were included in the study. The cytomorphologic features of these cases were analyzed. The FNA smears of other thyroid lesions with cystic changes (300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasm) were also studied. Results: The smears in CPTC revealed isolated follicular cells, small groups of cells with scalloped margins, cell swirls, small clusters with a cartwheel pattern, papillary clusters, intranuclear inclusions, nuclear grooves, sticky colloid, intracellular colloids, psammoma bodies, multinucleated giant cells, and foamy and hemosiderin laden macrophages. Small groups of cells with scalloped borders, cellular swirls, and small clusters with a cartwheel pattern were seen in CPTC, but not in other cystic lesions. Interestingly, mesothelial-like cells and hemophagocytic cells were seen in five and three cases of CPTC, respectively, but not in other cystic lesions. Conclusion: Mesothelial-like cells and hemophagocytic cells were observed in five and three cases of CPTC, respectively. Similar finding have not been previously reported in the literature. PMID:27756982

Primary hepatic lymphoma presenting as fulminant hepatic failure with hyperferritinemia: A case report

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Haider Fyeza S

2008-08-01

Full Text Available Abstract Introduction Primary hepatic lymphoma is an unusual form of non-Hodgkin's lymphoma that usually presents with constitutional symptoms, hepatomegaly and signs of cholestatic jaundice. Diffuse hepatic infiltration is uncommon and presentation with acute hepatic failure even more rare. The presence of markedly elevated ferritin levels can complicate the evaluation process and suggest alternative diagnoses. We present the case of a middle-aged woman exhibiting pancytopenia, hyperferritinemia and rapidly deteriorating to develop acute hepatic failure. Her initial clinical picture led to a working diagnosis of adult onset Still's disease with probable hemophagocytic syndrome before her worsening liver function necessitated a percutaneous liver biopsy and establishment of the final diagnosis of primary hepatic lymphoma. Conclusion Primary hepatic lymphoma is an uncommon malignancy and its manifestation as progressive hepatitis or acute fulminant hepatic failure can be difficult to diagnose. The presence of constitutional symptoms, pancytopenia and high ferritin levels can complicate the evaluation process. A liver biopsy early in the course of liver dysfunction may establish the diagnosis without a higher risk of bleeding complications seen once liver failure sets in.

Clinicopathological associations of acquired erythroblastopenia.

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Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

2015-01-01

Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated.

Clinical reasoning of nursing students on clinical placement: Clinical educators' perceptions.

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Hunter, Sharyn; Arthur, Carol

2016-05-01

Graduate nurses may have knowledge and adequate clinical psychomotor skills however they have been identified as lacking the clinical reasoning skills to deliver safe, effective care suggesting contemporary educational approaches do not always facilitate the development of nursing students' clinical reasoning. While nursing literature explicates the concept of clinical reasoning and develops models that demonstrate clinical reasoning, there is very little published about nursing students and clinical reasoning during clinical placements. Semi-structured interviews were conducted with ten clinical educators to gain an understanding of how they recognised, developed and appraised nursing students' clinical reasoning while on clinical placement. This study found variability in the clinical educators' conceptualisation, recognition, and facilitation of students' clinical reasoning. Although most of the clinical educators conceptualised clinical reasoning as a process those who did not demonstrated the greatest variability in the recognition and facilitation of students' clinical reasoning. The clinical educators in this study also described being unable to adequately appraise a student's clinical reasoning during clinical placement with the use of the current performance assessment tool. Copyright © 2016 Elsevier Ltd. All rights reserved.

Marking out the clinical expert/clinical leader/clinical scholar: perspectives from nurses in the clinical arena.

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Mannix, Judy; Wilkes, Lesley; Jackson, Debra

2013-01-01

Clinical scholarship has been conceptualised and theorised in the nursing literature for over 30 years but no research has captured nurses' clinicians' views on how it differs or is the same as clinical expertise and clinical leadership. The aim of this study was to determine clinical nurses' understanding of the differences and similarities between the clinical expert, clinical leader and clinical scholar. A descriptive interpretative qualitative approach using semi-structured interviews with 18 practising nurses from Australia, Canada and England. The audio-taped interviews were transcribed and the text coded for emerging themes. The themes were sorted into categories of clinical expert, clinical leader and clinical scholarship as described by the participants. These themes were then compared and contrasted and the essential elements that characterise the nursing roles of the clinical expert, clinical leader and clinical scholar were identified. Clinical experts were seen as linking knowledge to practice with some displaying clinical leadership and scholarship. Clinical leadership is seen as a positional construct with a management emphasis. For the clinical scholar they linked theory and practice and encouraged research and dissemination of knowledge. There are distinct markers for the roles of clinical expert, clinical leader and clinical scholar. Nurses working in one or more of these roles need to work together to improve patient care. An 'ideal nurse' may be a blending of all three constructs. As nursing is a practice discipline its scholarship should be predominantly based on clinical scholarship. Nurses need to be encouraged to go beyond their roles as clinical leaders and experts to use their position to challenge and change through the propagation of knowledge to their community.

Marking out the clinical expert/clinical leader/clinical scholar: perspectives from nurses in the clinical arena

Science.gov (United States)

2013-01-01

Background Clinical scholarship has been conceptualised and theorised in the nursing literature for over 30 years but no research has captured nurses’ clinicians’ views on how it differs or is the same as clinical expertise and clinical leadership. The aim of this study was to determine clinical nurses’ understanding of the differences and similarities between the clinical expert, clinical leader and clinical scholar. Methods A descriptive interpretative qualitative approach using semi-structured interviews with 18 practising nurses from Australia, Canada and England. The audio-taped interviews were transcribed and the text coded for emerging themes. The themes were sorted into categories of clinical expert, clinical leader and clinical scholarship as described by the participants. These themes were then compared and contrasted and the essential elements that characterise the nursing roles of the clinical expert, clinical leader and clinical scholar were identified. Results Clinical experts were seen as linking knowledge to practice with some displaying clinical leadership and scholarship. Clinical leadership is seen as a positional construct with a management emphasis. For the clinical scholar they linked theory and practice and encouraged research and dissemination of knowledge. Conclusion There are distinct markers for the roles of clinical expert, clinical leader and clinical scholar. Nurses working in one or more of these roles need to work together to improve patient care. An ‘ideal nurse’ may be a blending of all three constructs. As nursing is a practice discipline its scholarship should be predominantly based on clinical scholarship. Nurses need to be encouraged to go beyond their roles as clinical leaders and experts to use their position to challenge and change through the propagation of knowledge to their community. PMID:23587282

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

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Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

A review of histiocytic diseases of dogs and cats.

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Moore, P F

2014-01-01

Histiocytic proliferative disorders are commonly observed in dogs and less often cats. Histiocytic disorders occur in most of the dendritic cell (DC) lineages. Canine cutaneous histiocytoma originates from Langerhans cells (LCs) indicated by expression of CD1a, CD11c/CD18, and E-cadherin. When histiocytomas occur as multiple lesions in skin with optional metastasis to lymph nodes and internal organs, the disease resembles cutaneous Langerhans cell histiocytosis of humans. Langerhans cell disorders do not occur in feline skin. Feline pulmonary LCH has been recognized as a cause of respiratory failure due to diffuse pulmonary infiltration by histiocytes, which express CD18 and E-cadherin and contain Birbeck's granules. In dogs and cats, histiocytic sarcomas (HS) arise from interstitial DCs that occur in most tissues of the body. Histiocytic sarcomas begin as localized lesions, which rapidly disseminate to many organs. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An indolent form of localized HS, progressive histiocytosis, originates in the skin of cats. Hemophagocytic HS originates in splenic red pulp and bone marrow macrophages in dogs and cats. In dogs, histiocytes in hemophagocytic HS express CD11d/CD18, which is a leuko-integrin highly expressed by macrophages in splenic red pulp and bone marrow. Canine reactive histiocytic diseases, systemic histiocytosis (SH) and cutaneous histiocytosis, are complex inflammatory diseases with underlying immune dysregulation. The lesions are dominated by activated interstitial DCs and lymphocytes, which invade vessel walls and extend as vasocentric infiltrates in skin, lymph nodes, and internal organs (SH).

Marking out the clinical expert/clinical leader/clinical scholar: perspectives from nurses in the clinical arena

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Mannix, Judy; Wilkes, Lesley; Jackson, Debra

2013-01-01

Background Clinical scholarship has been conceptualised and theorised in the nursing literature for over 30?years but no research has captured nurses? clinicians? views on how it differs or is the same as clinical expertise and clinical leadership. The aim of this study was to determine clinical nurses? understanding of the differences and similarities between the clinical expert, clinical leader and clinical scholar. Methods A descriptive interpretative qualitative approach using semi-struct...

Comprehensive genetic testing for primary immunodeficiency disorders in a tertiary hospital: 10-year experience in Auckland, New Zealand.

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Woon, See-Tarn; Ameratunga, Rohan

2016-01-01

New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs). Since 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014. We undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity. Thorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.

Animal in vivo models of EBV-associated lymphoproliferative diseases: special references to rabbit models.

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Hayashi, K; Teramoto, N; Akagi, T

2002-10-01

Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on our two newly-developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82-89%) during 2-5 months. EBV-DNA was detected in peripheral blood by PCR from 2 days after oral inoculation, while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, during 22-105 days. Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens.

Clinical professional governance for detailed clinical models.

Science.gov (United States)

Goossen, William; Goossen-Baremans, Anneke

2013-01-01

This chapter describes the need for Detailed Clinical Models for contemporary Electronic Health Systems, data exchange and data reuse. It starts with an explanation of the components related to Detailed Clinical Models with a brief summary of knowledge representation, including terminologies representing clinic relevant "things" in the real world, and information models that abstract these in order to let computers process data about these things. Next, Detailed Clinical Models are defined and their purpose is described. It builds on existing developments around the world and accumulates in current work to create a technical specification at the level of the International Standards Organization. The core components of properly expressed Detailed Clinical Models are illustrated, including clinical knowledge and context, data element specification, code bindings to terminologies and meta-information about authors, versioning among others. Detailed Clinical Models to date are heavily based on user requirements and specify the conceptual and logical levels of modelling. It is not precise enough for specific implementations, which requires an additional step. However, this allows Detailed Clinical Models to serve as specifications for many different kinds of implementations. Examples of Detailed Clinical Models are presented both in text and in Unified Modelling Language. Detailed Clinical Models can be positioned in health information architectures, where they serve at the most detailed granular level. The chapter ends with examples of projects that create and deploy Detailed Clinical Models. All have in common that they can often reuse materials from earlier projects, and that strict governance of these models is essential to use them safely in health care information and communication technology. Clinical validation is one point of such governance, and model testing another. The Plan Do Check Act cycle can be applied for governance of Detailed Clinical Models

Clinical Trials

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Full Text Available ... Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... and Clinical Studies Web page. Children and Clinical Studies Learn more about Children and Clinical Studies Importance ...

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Full Text Available ... questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical ... multi-pronged approach to Optimize our Clinical Trials Enterprise that will make our clinical trials enterprise even ...

Clinical Trials

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Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... humans. What Are Clinical Trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or ...

Maintenance of Clinical Expertise and Clinical Research by the Clinical Professors at Gifu Pharmaceutical University.

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Tachi, Tomoya; Noguchi, Yoshihiro; Teramachi, Hitomi

2017-01-01

The clinical professors at Gifu Pharmaceutical University (GPU) provide pharmaceutical services at GPU Pharmacy, Gifu University Hospital, and Gifu Municipal Hospital to keep their clinical skills up-to-date; they also perform clinical research in collaboration with many clinical institutes. The Laboratory of Clinical Pharmacy is part of the Department of Pharmacy Practice and Science, to which the clinical professors belong, and is composed of three clinical professors (a professor, an associate professor, and an assistant professor). The professor administers the GPU Pharmacy as its director, while the associate professor and assistant professor provide pharmaceutical services to patients at Gifu Municipal Hospital, and also provide practical training for students in the GPU Pharmacy. Collectively, they have performed research on such topics as medication education for students, clinical communication education, and analysis of clinical big data. They have also conducted research in collaboration with clinical institutes, hospitals, and pharmacies. Here, we introduce the collaborative research between the Laboratory of Clinical Pharmacy and Gifu Municipal Hospital. These studies include "Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy", "Hyponatremia and hypokalemia as risk factors for falls", "Economic evaluation of adjustments of levofloxacin dosage by dispensing pharmacists for patients with renal dysfunction", and "Effect of patient education upon discharge for use of a medication notebook on purchasing over-the-counter drugs and health foods". In this symposium, we would like to demonstrate one model of the association and collaborative research between these clinical professors and clinical institutes.

Interleukin-18 and interleukin-18 Binding Protein

Directory of Open Access Journals (Sweden)

Charles eDinarello

2013-10-01

Full Text Available Interleukin-18 (IL 18 is a member of the IL 1 family of cytokines. Increasing reports have expanded the role of IL 18 in mediating inflammation in animal models of disease using IL 18 deficient mice, neutralization of IL 18 or deficiency in the IL 18 receptor alpha chain. Similar to IL 1β, IL 18 is synthesized as an inactive precursor requiering processing by caspase 1 into an active cytokine but unlike IL 1β, the IL 18 precursor is constitutively present in nearly all cells in healthy humans and animals. The activity of IL 18 is balanced by the presence of a high-affinity naturally occuring IL 18 binding protein (IL 18BP. In humans, disease increased disease severity can be associated with an imbalance of IL 18 to IL 18BP such that the levels of free IL 18 are elevated in the circulation. A role for IL 18 has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, hemophagocytic syndromes, macrophage activation syndrome, sepsis and acute kidney injury, although in some diseases, IL 18 is protective. IL 18 plays a major role in the production of interferon-g from natural killer cells. The IL 18BP has been used safely in humans and clinical trials of IL 18BP as well as neutralizing anti-IL 18 antibodies are in clinical trials. This review updates the biology of IL 18 as well as its role in human disease

An Important Finding of Systemic Aspergillosis: Skin Involvement and Amphotericin B Resistance in an Adolescent

Directory of Open Access Journals (Sweden)

Aslinur Ozkaya-Parlakay

2016-08-01

Full Text Available Invasive aspergillosis is a life-threatening infectious complication in immunocompromised patients, especially with malignancy, and in some cases, it causes extensive tissue destruction and subsequent systemic illness, leading to multiorgan failure and death. Skin involvement and amphotericin B resistance are very rare findings of aspergillosis. Herein, we report the case of a primary hemophagocytic syndrome patient who developed subcutaneous nodules in the 3rd month of bone marrow transplantation from which Aspergillus fumigatus was cultivated despite the fact that she was under antifungal therapy. In immunocompromised patients with prolonged fever, atypical presentations of invasive mycosis should be kept in mind, and early appropriate therapy should be initiated promptly to decrease morbidity and mortality.

Clinical Pharmacopsychology

DEFF Research Database (Denmark)

Fava, Giovanni A.; Tomba, Elena; Bech, Per

2017-01-01

of its most representative expressions and reference to current challenges of clinical research, with particular reference to clinimetrics. The domains of clinical pharmacopsychology encompass the clinical benefits of psychotropic drugs, the characteristics that predict responsiveness to treatment...... effects, (b) treatment-induced unwanted side effects, and (c) the patient's own personal experience of a change in terms of well-being and/or quality of life. Clinical pharmacopsychology offers a unifying framework for the understanding of clinical phenomena in medical and psychiatric settings. Research......The aim of this critical review was to outline emerging trends and perspectives of clinical pharmacopsychology, an area of clinical psychology that is concerned with the psychological effects of medications. The historical development of clinical pharmacopsychology is outlined, with discussion...

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Construction of ethics in clinical research: clinical trials registration

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C. A. Caramori

2007-01-01

Full Text Available Scientific development that has been achieved through decades finds in clinical research a great possibility of translating findings to human health application. Evidence given by clinical trials allows everyone to have access to the best health services. However, the millionaire world of pharmaceutical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials and scientific publications (selective, manipulated and with wrong conclusions led to an inappropriate clinical practice, favoring the involved economic aspect. In 2005, the International Committee of Medical Journal Editors (ICMJE, supported by the World Association of Medical Editors, started demanding as a requisite for publication that all clinical trials be registered at the database ClinicalTrials.gov. In 2006, the World Health Organization (WHO created the International Clinical Trial Registry Platform (ICTRP, which gathers several registry centers from all over the world, and required that all researchers and pharmaceutical industries register clinical trials. Such obligatory registration has progressed and will extend to all scientific journals indexed in all worldwide databases. Registration of clinical trials means another step of clinical research towards transparency, ethics and impartiality, resulting in real evidence to the forthcoming changes in clinical practice as well as in the health situation.

Clinical Trials

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Full Text Available ... clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a ... will be done during the clinical trial and why. Each medical center that does the study uses ...

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Full Text Available ... Studies Learn more about Children and Clinical Studies Importance of Children in Clinical Studies Children have often ... participants. Children and Clinical Studies Learn about the importance of children in clinical studies and get answers ...

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Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...

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Full Text Available ... Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... tool for advancing medical knowledge and patient care. Clinical research is done only if doctors don't know ...

Clinical Reasoning Terms Included in Clinical Problem Solving Exercises?

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Musgrove, John L; Morris, Jason; Estrada, Carlos A; Kraemer, Ryan R

2016-05-01

Background Published clinical problem solving exercises have emerged as a common tool to illustrate aspects of the clinical reasoning process. The specific clinical reasoning terms mentioned in such exercises is unknown. Objective We identified which clinical reasoning terms are mentioned in published clinical problem solving exercises and compared them to clinical reasoning terms given high priority by clinician educators. Methods A convenience sample of clinician educators prioritized a list of clinical reasoning terms (whether to include, weight percentage of top 20 terms). The authors then electronically searched the terms in the text of published reports of 4 internal medicine journals between January 2010 and May 2013. Results The top 5 clinical reasoning terms ranked by educators were dual-process thinking (weight percentage = 24%), problem representation (12%), illness scripts (9%), hypothesis generation (7%), and problem categorization (7%). The top clinical reasoning terms mentioned in the text of 79 published reports were context specificity (n = 20, 25%), bias (n = 13, 17%), dual-process thinking (n = 11, 14%), illness scripts (n = 11, 14%), and problem representation (n = 10, 13%). Context specificity and bias were not ranked highly by educators. Conclusions Some core concepts of modern clinical reasoning theory ranked highly by educators are mentioned explicitly in published clinical problem solving exercises. However, some highly ranked terms were not used, and some terms used were not ranked by the clinician educators. Effort to teach clinical reasoning to trainees may benefit from a common nomenclature of clinical reasoning terms.

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Full Text Available ... child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Clinical trials for children have the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ...

Clinical Trials

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Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key ... Enterprise NHLBI has a strong tradition of supporting clinical trials that have not only shaped medical practice around the world, but have improved the health ...

Clinical Trials

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Full Text Available ... resources to the strategies and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, you may get tests or treatments in a hospital, clinic, or doctor's office. In some ways, taking part in a clinical trial is different ...

Pursuing Improvement in Clinical Reasoning: The Integrated Clinical Education Theory.

Science.gov (United States)

Jessee, Mary Ann

2018-01-01

The link between clinical education and development of clinical reasoning is not well supported by one theoretical perspective. Learning to reason during clinical education may be best achieved in a supportive sociocultural context of nursing practice that maximizes reasoning opportunities and facilitates discourse and meaningful feedback. Prelicensure clinical education seldom incorporates these critical components and thus may fail to directly promote clinical reasoning skill. Theoretical frameworks supporting the development of clinical reasoning during clinical education were evaluated. Analysis of strengths and gaps in each framework's support of clinical reasoning development was conducted. Commensurability of philosophical underpinnings was confirmed, and complex relationships among key concepts were elucidated. Six key concepts and three tenets comprise an explanatory predictive theory-the integrated clinical education theory (ICET). ICET provides critical theoretical support for inquiry and action to promote clinical education that improves development of clinical reasoning skill. [J Nurs Educ. 2018;57(1):7-13.]. Copyright 2018, SLACK Incorporated.

Clinical Trials

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Full Text Available ... about your health or fill out forms about how you feel. Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place ...

Clinical Trials

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Full Text Available ... part in a clinical trial is your decision. Talk with your doctor about all of your treatment options. Together, you can make the ... more about, or taking part in, clinical trials, talk with your doctor. He or she may know about ... clinical trials. NIH Clinical Research Studies ...

Connecting Classroom, Clinic, and Context: Clinical Reasoning Strategies for Clinical Instructors and Academic Faculty.

Science.gov (United States)

Furze, Jennifer; Kenyon, Lisa K; Jensen, Gail M

2015-01-01

Clinical reasoning is an essential skill in pediatric physical therapist (PT) practice. As such, explicit instruction in clinical reasoning should be emphasized in PT education. This article provides academic faculty and clinical instructors with an overview of strategies to develop and expand the clinical reasoning capacity of PT students within the scope of pediatric PT practice. Achieving a balance between deductive reasoning strategies that provide a framework for thinking and inductive reasoning strategies that emphasize patient factors and the context of the clinical situation is an important variable in educational pedagogy. Consideration should be given to implementing various teaching and learning approaches across the curriculum that reflect the developmental level of the student(s). Deductive strategies may be helpful early in the curriculum, whereas inductive strategies are often advantageous after patient interactions; however, exposure to both is necessary to fully develop the learner's clinical reasoning abilities. For more insights from the authors, see Supplemental Digital Content 1, available at http://links.lww.com/PPT/A87.

Clinical Trials

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Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...

42 CFR 405.2450 - Clinical psychologist and clinical social worker services.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Clinical psychologist and clinical social worker... § 405.2450 Clinical psychologist and clinical social worker services. (a) For clinical psychologist or clinical social worker professional services to be payable under this subpart, the services must be— (1...

Anaplasma phagocytophilum-Related Defects in CD8, NKT, and NK Lymphocyte Cytotoxicity

Directory of Open Access Journals (Sweden)

Diana G. Scorpio

2018-04-01

Full Text Available Human granulocytic anaplasmosis, caused by the tick-transmitted Anaplasma phagocytophilum, is not controlled by innate immunity, and induces a proinflammatory disease state with innate immune cell activation. In A. phagocytophilum murine infection models, hepatic injury occurs with production of IFNγ thought to be derived from NK, NKT cells, and CD8 T lymphocytes. Specific A. phagocytophilum ligands that drive inflammation and disease are not known, but suggest a clinical and pathophysiologic basis strikingly like macrophage activation syndrome (MAS and hemophagocytic syndrome (HPS. We studied in vivo responses of NK, NKT, and CD8 T lymphocytes from infected animals for correlates of lymphocyte-mediated cytotoxicity and examined in vitro interactions with A. phagocytophilum-loaded antigen-presenting cells (APCs. Murine splenocytes were examined and found deficient in cytotoxicity as determined by CD107a expression in vitro for specific CTL effector subsets as determined by flow cytometry. Moreover, A. phagocytophilum-loaded APCs did not lead to IFNγ production among CTLs in vitro. These findings support the concept of impaired cytotoxicity with A. phagocytophilum presentation by APCs that express MHC class I and that interact with innate and adaptive immune cells with or after infection. The findings strengthen the concept of an enhanced proinflammatory phenotype, such as MAS and HPS disease states as the basis of disease and severity with A. phagocytophilum infection, and perhaps by other obligate intracellular bacteria.

Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort.

Science.gov (United States)

Riveros Frutos, A; Casas, I; Rúa-Figueroa, I; López-Longo, F J; Calvo-Alén, J; Galindo, M; Fernández-Nebro, A; Pego-Reigosa, J M; Olivé Marqués, A

2017-06-01

Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18-92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p lupus nephritis was more common in men, being present in 155 (44.8%) of males versus 933 (29%) of females ( p  50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50 years have an increased risk of mortality. In Caucasians, age at diagnosis and symptom onset is higher in men than in women. The diagnostic delay is shorter in men. Male SLE patients present more cardiovascular comorbidities, and also more serositis, adenopathies, splenomegaly, renal involvement, convulsion, thrombosis, and lupus anticoagulant positivity than women.

Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

Science.gov (United States)

Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

2017-11-01

Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Trials

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Full Text Available ... the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ... based on what is known to work in adults. To improve clinical care of children, more studies ...

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Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

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Full Text Available ... or vulnerable patients (such as children). A DSMB's role is to review data from a clinical trial ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

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Full Text Available ... you to explore NIH Clinical Center for patient recruitment and clinical trial information. For more information, please email the NIH Clinical Center Office of Patient Recruitment at cc-prpl@cc.nih.gov or call ...

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Full Text Available ... clinical trials are vital to the process of improving medical care. Many people volunteer because they want ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

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Full Text Available ... comparison groups by chance, rather than choice. This method helps ensure that any differences observed during a ... to learn more about clinical research and to search for clinical trials: NHLBI Clinical Trials Browse a ...

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Full Text Available ... these results are important because they advance medical knowledge and help improve patient care. Sponsorship and Funding ... All types of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical ...

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Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are ... earlier than they would be in general medical practice. This is because late-phase trials have large ...

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Full Text Available ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies ... parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, ...

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Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human ...

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Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... to learn more about clinical research and to search for clinical trials: NHLBI Clinical Trials Browse a ...

Physiotherapy clinical educators' perceptions and experiences of clinical prediction rules.

Science.gov (United States)

Knox, Grahame M; Snodgrass, Suzanne J; Rivett, Darren A

2015-12-01

Clinical prediction rules (CPRs) are widely used in medicine, but their application to physiotherapy practice is more recent and less widespread, and their implementation in physiotherapy clinical education has not been investigated. This study aimed to determine the experiences and perceptions of physiotherapy clinical educators regarding CPRs, and whether they are teaching CPRs to students on clinical placement. Cross-sectional observational survey using a modified Dillman method. Clinical educators (n=211, response rate 81%) supervising physiotherapy students from 10 universities across 5 states and territories in Australia. Half (48%) of respondents had never heard of CPRs, and a further 25% had never used CPRs. Only 27% reported using CPRs, and of these half (51%) were rarely if ever teaching CPRs to students in the clinical setting. However most respondents (81%) believed CPRs assisted in the development of clinical reasoning skills and few (9%) were opposed to teaching CPRs to students. Users of CPRs were more likely to be male (pphysiotherapy (pStudents are unlikely to be learning about CPRs on clinical placement, as few clinical educators use them. Clinical educators will require training in CPRs and assistance in teaching them if students are to better learn about implementing CPRs in physiotherapy clinical practice. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Pre-clinical medical student experience in a pediatric pulmonary clinic

Directory of Open Access Journals (Sweden)

Thomas G. Saba

2015-11-01

Full Text Available Objective: Our objective was to evaluate the educational value of introducing pre-clinical medical students to pediatric patients and their families in a subspecialty clinic setting. Methods: First- and second-year medical students at the University of Michigan seeking clinical experience outside of the classroom attended an outpatient pediatric pulmonary clinic. Evaluation of the experience consisted of pre- and post-clinic student surveys and post-clinic parent surveys with statements employing a four-point Likert scale as well as open-ended questions. Results: Twenty-eight first-year students, 6 second-year students, and 33 parents participated in the study. Post-clinic statement scores significantly increased for statements addressing empathic attitudes, confidence communicating with children and families, comfort in the clinical environment, and social awareness. Scores did not change for statements addressing motivation, a sense of team membership, or confidence with career goals. Students achieved their goals of gaining experience interacting with patients, learning about pulmonary diseases, and observing clinic workflow. Parents felt that they contributed to student education and were not inconvenienced. Conclusions: Students identified several educational benefits of exposure to a single pediatric pulmonary clinic. Patients and families were not inconvenienced by the participation of a student. Additional studies are warranted to further investigate the value of this model of pre-clinical medical student exposure to subspecialty pediatrics.

Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

Directory of Open Access Journals (Sweden)

Simon Krabbe

2016-01-01

Full Text Available This case report describes a patient with arthritis of the large joints, bilateral sacroiliitis, and positive anti-SSA and anti-dsDNA antibody, who received sulfasalazine and shortly thereafter became critically ill. He developed toxic epidermal necrolysis, hemolytic anemia, lymphopenia, markedly elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations.

Construction of ethics in clinical research: clinical trials registration

OpenAIRE

C. A. Caramori

2007-01-01

Scientific development that has been achieved through decades finds in clinical research a great possibility of translating findings to human health application. Evidence given by clinical trials allows everyone to have access to the best health services. However, the millionaire world of pharmaceutical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials) and scientific publications (selective, manipulated and with wrong c...

Clinical Trials

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Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...

Clinical Trials

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Full Text Available ... give permission for their child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Find a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

Optimal use of MRI in clinical trials, clinical care and clinical registries of patients with rheumatoid arthritis

DEFF Research Database (Denmark)

Østergaard, Mikkel; Møller-Bisgaard, Signe

2014-01-01

the benefits of including MRI in treat-to-target strategies. The benefits of incorporating MRI into clinical registries are not yet known, but may include improved knowledge about the real-life advantages of MRI, as well as opportunities to develop better clinical and laboratory composite measures to monitor......Magnetic resonance imaging (MRI) clearly is more sensitive than clinical examination and conventional radiography (x-ray) for detection of inflammation (synovitis, bone marrow oedema (osteitis) and tenosynovitis) and damage (bone erosion and cartilage loss/joint space narrowing) in patients...... with rheumatoid arthritis (RA). The question is when and how MRI should be used. The present article reviews our knowledge about, and provides suggestions for, the use of MRI in clinical trials, clinical care and clinical registries. In clinical trials, the OMERACT RA MRI scoring system (RAMRIS) is a thoroughly...

Communities of clinical practice: the social organization of clinical learning.

Science.gov (United States)

Egan, Tony; Jaye, Chrystal

2009-01-01

The social organization of clinical learning is under-theorized in the sociological literature on the social organization of health care. Professional scopes of practice and jurisdictions are formally defined by professional principles and standards and reflected in legislation; however, these are mediated through the day-to-day clinical activities of social groupings of clinical teams. The activities of health service providers typically occur within communities of clinical practice. These are also major sites for clinical curriculum delivery, where clinical students learn not only clinical skills but also how to be health professionals. In this article, we apply Wenger's model of social learning within organizations to curriculum delivery within a health service setting. Here, social participation is the basis of learning. We suggest that it offers a powerful framework for recognizing and explaining paradox and incongruence in clinical teaching and learning, and also for recognizing opportunities, and devising means, to add value to students' learning experiences.

Improvement of Clinical Skills through Pharmaceutical Education and Clinical Research.

Science.gov (United States)

Ishizaki, Junko

2017-01-01

Professors and teaching staff in the field of pharmaceutical sciences should devote themselves to staying abreast of relevant education and research. Similarly those in clinical pharmacies should contribute to the advancement of pharmaceutical research and the development of next generation pharmacists and pharmaceuticals. It is thought that those who work in clinical pharmacies should improve their own skills and expertise in problem-finding and -solving, i.e., "clinical skills". They should be keen to learn new standard treatments based on the latest drug information, and should try to be in a position where collecting clinical information is readily possible. In the case of pharmacists in hospitals and pharmacies, they are able to aim at improving their clinical skills simply through performing their pharmaceutical duties. On the other hand, when a pharmaceutical educator aims to improve clinical skills at a level comparable to those of clinical pharmacists, it is necessary to devote or set aside considerable time for pharmacist duties, in addition to teaching, which may result in a shortage of time for hands-on clinical practice and/or in a decline in the quality of education and research. This could be a nightmare for teaching staff in clinical pharmacy who aim to take part in such activities. Nonetheless, I believe that teaching staff in the clinical pharmacy area could improve his/her clinical skills through actively engaging in education and research. In this review, I would like to introduce topics on such possibilities from my own experiences.

Clinical Trials

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Full Text Available ... benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials ... child to enroll. Also, children aged 7 and older often must agree (assent) to ... as clinical trials for adults. For more information, go to "How Do Clinical ...

Opioid detoxification : from controlled clinical trial to clinical practice

NARCIS (Netherlands)

Dijkstra, Boukje A G; De Jong, Cor A J; Wensing, Michel; Krabbe, Paul F M; van der Staak, Cees P F

2010-01-01

Controlled clinical trials have high internal validity but suffer from difficulties in external validity. This study evaluates the generalizability of the results of a controlled clinical trial on rapid detoxification in the everyday clinical practice of two addiction treatment centers. The results

Clinical Studies

DEFF Research Database (Denmark)

Pallesen, Ulla

universities and practicing dentists restore millions of teeth throughout the World with composite resin materials. Do we know enough about the clinical performance of these restorations over time? Numerous in vitro studies are being published on resin materials and adhesion, some of them attempting to imitate...... in vivo conditions. But real life is different and in vitro studies cannot include all variables. Only clinical studies can provide valid information on the clinical performance of restorations over time. What do we know about longevity of posterior resin restorations? What are the reasons for replacement...... and results from own up to 30-year prospective clinical university studies and practice based studies from Public Dental Health Service on the clinical performance of posterior composite resin restorations....

Integrating clinical communication with clinical reasoning and the broader medical curriculum.

Science.gov (United States)

Cary, Julie; Kurtz, Suzanne

2013-09-01

The objectives of this paper are to discuss the results of a workshop conducted at EACH 2012. Specifically, we will (1) examine the link between communication, clinical reasoning, and medical problem solving, (2) explore strategies for (a) integrating clinical reasoning, medical problem solving, and content from the broader curriculum into clinical communication teaching and (b) integrating communication into the broader curriculum, and (3) discuss benefits gained from such integration. Salient features from the workshop were recorded and will be presented here, as well as a case example to illustrate important connections between clinical communication and clinical reasoning. Potential links between clinical communication, clinical reasoning, and medical problem solving as well as strategies to integrate clinical communication teaching and the broader curricula in human and veterinary medicine are enumerated. Participants expressed enthusiasm and keen interest in integration of clinical communication teaching and clinical reasoning during this workshop, came to the idea of the interdependence of these skills easily, and embraced the rationale immediately. Valuing the importance of communication as clinical skill and embracing the interdependence between communication and thought processes related to clinical reasoning and medical problem solving will be beneficial in teaching programs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Clinical Trials

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Full Text Available ... clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about ...

Clinical leadership in contemporary clinical practice: implications for nursing in Australia.

Science.gov (United States)

Davidson, P M; Elliott, D; Daly, J

2006-04-01

Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.

Clinical education and clinical evaluation of respiratory therapy students.

Science.gov (United States)

Cullen, Deborah L

2005-09-01

Different blends of knowledge, decision making, problem solving,professional behaviors, values, and technical skills are necessary in the changing health care environments in which respiratory therapists practice. Frequently, novice students are expected to perform quickly and efficiently,and it may be forgotten that students are still learning and mastering the foundation pieces of practice. Clinical educators take on the responsibility of student development in addition to overseeing patient care. Normally,these volunteer instructors are role models for respiratory therapy students. The characteristic of initiative when demonstrated by a beginning student is attractive to the clinical instructor, promotes sharing of experiences, and may evolve into a mentor-protege relationship. Some clinical instructors may be underprepared to teach and are uncomfortable with student evaluation. Respiratory therapy facilities in conjunction with academic institutions may consider sponsoring ongoing programs for clinical teachers. Teaching and learning in the clinical environment is more than demonstration of skills and knowledge. Furthermore, it can be debated whether the memorization of facts or of the steps of a skill is more valuable than competency in problem solving, clinical reasoning, or information retrieval. New knowledge is built within a context and is further integrated when grounded by experience. Development of "prediction in practice" or the anticipation of the next necessary actions may be worth integrating into the instructional toolbox. Intuition has been defined as an "understanding without a rationale". This definition separates intuition from rational decision making and presents intuition as a type of innate ability. Reflection when guided by clinical instructors can help deepen critical thinking, as will Socratic questioning on a regular basis. Most clinical staff can agree on the performance of an incompetent student, but discrimination of the levels of

Clinical mastitis in ewes; bacteriology, epidemiology and clinical features

Directory of Open Access Journals (Sweden)

Kvitle Bjørg

2007-09-01

Full Text Available Abstract Background Clinical mastitis is an important disease in sheep. The objective of this work was to identify causal bacteria and study certain epidemiological and clinical features of clinical mastitis in ewes kept for meat and wool production. Methods The study included 509 ewes with clinical mastitis from 353 flocks located in 14 of the 19 counties in Norway. Clinical examination and collection of udder secretions were carried out by veterinarians. Pulsed-field gel electrophoresis (PFGE was performed on 92 Staphylococcus aureus isolates from 64 ewes. Results and conclusion S. aureus was recovered from 65.3% of 547 clinically affected mammary glands, coagulase-negative staphylococci from 2.9%, enterobacteria, mainly Escherichia coli, from 7.3%, Streptococcus spp. from 4.6%, Mannheimia haemolytica from 1.8% and various other bacteria from 4.9%, while no bacteria were cultured from 13.2% of the samples. Forty percent of the ewes with unilateral clinical S. aureus mastitis also had a subclinical S. aureus infection in the other mammary gland. Twenty-four of 28 (86% pairs of S. aureus isolates obtained from clinically and subclinically affected mammary glands of the same ewe were indistinguishable by PFGE. The number of identical pairs was significantly greater than expected, based on the distribution of different S. aureus types within the flocks. One-third of the cases occurred during the first week after lambing, while a second peak was observed in the third week of lactation. Gangrene was present in 8.8% of the clinically affected glands; S. aureus was recovered from 72.9%, Clostridium perfringens from 6.3% and E. coli from 6.3% of the secretions from such glands. This study shows that S. aureus predominates as a cause of clinical ovine mastitis in Norway, also in very severe cases. Results also indicate that S. aureus is frequently spread between udder halves of infected ewes.

Critical thinking versus clinical reasoning versus clinical judgment: differential diagnosis.

Science.gov (United States)

Victor-Chmil, Joyce

2013-01-01

Concepts of critical thinking, clinical reasoning, and clinical judgment are often used interchangeably. However, they are not one and the same, and understanding subtle difference among them is important. Following a review of the literature for definitions and uses of the terms, the author provides a summary focused on similarities and differences in the processes of critical thinking, clinical reasoning, and clinical judgment and notes suggested methods of measuring each.

Medical student resilience and stressful clinical events during clinical training.

Science.gov (United States)

Houpy, Jennifer C; Lee, Wei Wei; Woodruff, James N; Pincavage, Amber T

2017-01-01

Medical students face numerous stressors during their clinical years, including difficult clinical events. Fostering resilience is a promising way to mitigate negative effects of stressors, prevent burnout, and help students thrive after difficult experiences. However, little is known about medical student resilience. To characterize medical student resilience and responses to difficult clinical events during clinical training. Sixty-two third-year (MS3) and 55 fourth-year (MS4) University of Chicago medical students completed surveys in 2016 assessing resilience (Connor Davidson Resilience Scale, CD-RISC 10), symptoms of burnout, need for resilience training, and responses to difficult clinical events. Medical student mean resilience was lower than in a general population sample. Resilience was higher in males, MS4s, those without burnout symptoms, and students who felt able to cope with difficult clinical events. When students experienced difficult events in the clinical setting, the majority identified poor team dynamics among the most stressful, and agreed their wellbeing was affected by difficult clinical events. A majority also would prefer to discuss these events with their team later that day. Students discussed events with peers more than with attendings or residents. Students comfortable discussing stress and burnout with peers had higher resilience. Most students believed resilience training would be helpful and most beneficial during MS3 year. Clinical medical student resilience was lower than in the general population but higher in MS4s and students reporting no burnout. Students had some insight into their resilience and most thought resilience training would be helpful. Students discussed difficult clinical events most often with peers. More curricula promoting medical student resilience are needed.

Clinical epidemiology.

Science.gov (United States)

Martin, S W; Bonnett, B

1987-06-01

Rational clinical practice requires deductive particularization of diagnostic findings, prognoses, and therapeutic responses from groups of animals (herds) to the individual animal (herd) under consideration This process utilizes concepts, skills, and methods of epidemiology, as they relate to the study of the distribution and determinants of health and disease in populations, and casts them in a clinical perspective.We briefly outline diagnostic strategies and introduce a measure of agreement, called kappa, between clinical diagnoses. This statistic is useful not only as a measure of diagnostic accuracy, but also as a means of quantifying and understanding disagreement between diagnosticians. It is disconcerting to many, clinicians included, that given a general deficit of data on sensitivity and specificity, the level of agreement between many clinical diagnoses is only moderate at best with kappa values of 0.3 to 0.6.Sensitivity, specificity, pretest odds, and posttest probability of disease are defined and related to the interpretation of clinical findings and ancillary diagnostic test results. An understanding of these features and how they relate to ruling-in or ruling-out a diagnosis, or minimizzing diagnostic errors will greatly enhance the diagnostic accuracy of the practitioner, and reduce the frequency of clinical disagreement. The approach of running multiple tests on every patient is not only wasteful and expensive, it is unlikely to improve the ability of the clinician to establish the correct diagnosis.We conclude with a discussion of how to decide on the best therapy, a discussion which centers on, and outlines the key features of, the well designed clinical trial. Like a diagnosis, the results from a clinical trial may not always be definitive, nonetheless it is the best available method of gleaning information about treatment efficacy.

Clinical trial methodology

National Research Council Canada - National Science Library

Peace, Karl E; Chen, Ding-Geng

2011-01-01

... in the pharmaceutical industry, Clinical trial methodology emphasizes the importance of statistical thinking in clinical research and presents the methodology as a key component of clinical research...

A study on job satisfaction among clinical and non-clinical hospital ...

African Journals Online (AJOL)

Methods: Two hundred clinical and non-clinical hospital staff were invited to take part in the study. They completed a sociodemographic questionnaire and the Job Descriptive Index (JDI). Results: The results indicated that majority clinical and non-clinical staff were satisfied with their jobs as regards the parameters of the ...

Learning clinical reasoning.

Science.gov (United States)

Pinnock, Ralph; Welch, Paul

2014-04-01

Errors in clinical reasoning continue to account for significant morbidity and mortality, despite evidence-based guidelines and improved technology. Experts in clinical reasoning often use unconscious cognitive processes that they are not aware of unless they explain how they are thinking. Understanding the intuitive and analytical thinking processes provides a guide for instruction. How knowledge is stored is critical to expertise in clinical reasoning. Curricula should be designed so that trainees store knowledge in a way that is clinically relevant. Competence in clinical reasoning is acquired by supervised practice with effective feedback. Clinicians must recognise the common errors in clinical reasoning and how to avoid them. Trainees can learn clinical reasoning effectively in everyday practice if teachers provide guidance on the cognitive processes involved in making diagnostic decisions. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Clinical Trials

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Full Text Available ... Entire Site NHLBI Entire Site Health Topics News & Resources Intramural Research ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ...

F-18 FDG PET/CT Findings of Subcutaneous Panniculitis - Like T- Cell Lymphoma : A Case Report

International Nuclear Information System (INIS)

Kong, Eun Jung; Cho, Ihn Ho; Chun, Kyung Ah; Bae, Yeung Kyung; Choi, Joon Hyuk; Hyun, Myung Soo

2009-01-01

F-18 FDG PET is a metabolic imaging modality that is efficacious in staging and assessment of treatment response for variety of lymphomas. We report usefulness of F-18 FDG PET/CT in evaluating severity of the disease and response to therapy in a patient with subcutaneous panniculitis- like T-cell lymphoma (SPTCL). Here we describe a case of SPTCL in 24-year-old man who had wide spread firm and tender nodular lesions with increased F-18 FDG uptake. After chemotherapy follow up F-18 FDG PET/CT image shows disseminated malignancy and then the patient died with hemophagocytic syndrome. This report suggests that F-18 FDG PET/CT may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected outcome of SPTCL

Assuring Quality Control of Clinical Education in Multiple Clinical Affiliates.

Science.gov (United States)

Davis, Judith A.

A plan was developed to assure equivalency of clinical education among the medical laboratory technician (MLT) programs affiliated with Sandhills Community College. The plan was designed by faculty to monitor the quality of clinical courses offered by the clinical affiliates. The major strategies were to develop competencies, slide/tape modules, a…

Clinical Trials

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Full Text Available ... to main content U.S. Department of Health & Human ... of people. Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ...

Clinical Trials

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Full Text Available ... risks that outweigh any possible benefits. Clinical Trial Phases Clinical trials of new medicines or medical devices are done in phases. These phases have different purposes and help researchers ...

Understanding Clinical Trials

Science.gov (United States)

Watch these videos to learn about some basic aspects of cancer clinical trials such as the different phases of clinical trials, methods used to protect patient safety, and how the costs of clinical trials are covered.

Overgeneral autobiographical memory bias in clinical and non-clinical voice hearers.

Science.gov (United States)

Jacobsen, Pamela; Peters, Emmanuelle; Ward, Thomas; Garety, Philippa A; Jackson, Mike; Chadwick, Paul

2018-03-14

Hearing voices can be a distressing and disabling experience for some, whilst it is a valued experience for others, so-called 'healthy voice-hearers'. Cognitive models of psychosis highlight the role of memory, appraisal and cognitive biases in determining emotional and behavioural responses to voices. A memory bias potentially associated with distressing voices is the overgeneral memory bias (OGM), namely the tendency to recall a summary of events rather than specific occasions. It may limit access to autobiographical information that could be helpful in re-appraising distressing experiences, including voices. We investigated the possible links between OGM and distressing voices in psychosis by comparing three groups: (1) clinical voice-hearers (N = 39), (2) non-clinical voice-hearers (N = 35) and (3) controls without voices (N = 77) on a standard version of the autobiographical memory test (AMT). Clinical and non-clinical voice-hearers also completed a newly adapted version of the task, designed to assess voices-related memories (vAMT). As hypothesised, the clinical group displayed an OGM bias by retrieving fewer specific autobiographical memories on the AMT compared with both the non-clinical and control groups, who did not differ from each other. The clinical group also showed an OGM bias in recall of voice-related memories on the vAMT, compared with the non-clinical group. Clinical voice-hearers display an OGM bias when compared with non-clinical voice-hearers on both general and voices-specific recall tasks. These findings have implications for the refinement and targeting of psychological interventions for psychosis.

Student centredness in clinical learning: the influence of the clinical teacher.

Science.gov (United States)

Newton, Jennifer M; Jolly, Brian C; Ockerby, Cherene M; Cross, Wendy M

2012-10-01

This article reports a longitudinal study examining how nursing students learn on clinical placements in three cohorts of undergraduates at a large Australian university. Preceptorship models of clinical learning are increasing in popularity as a strategy to maximize collaboration between university and healthcare organizations. A clinical education model, underpinned by preceptorship, was offered by an Australian university in partnership with a tertiary healthcare organization to some students. The study utilized a mixed method approach of surveys and interviews. It was hypothesized that students participating in the preceptorship partnership model would have more positive perceptions of the clinical learning environment than students participating in other models of clinical education. Data were collected over 3 years, from 2006-2008, using a modified Clinical Learning Environment Inventory from second (n = 396) and third (n = 263) year nursing students. Students were classified into three groups based on which educational model they received. On the inventory factor, 'Student centredness', a Welch test indicated an important difference between the responses of students in the three groups. Games-Howell post hoc test indicated that students in the clinical preceptorship partnership model responded more positively than students who had both a clinical teacher and a preceptor in a non-preceptorship partnership model. Developing sustainable approaches to enhance the clinical learning environment experience for student nurses is an international concern. The significance of continuity of clinical teachers to the contribution of student centredness is an important aspect to be considered. © 2012 Blackwell Publishing Ltd.

How GPs implement clinical guidelines in everyday clinical practice

DEFF Research Database (Denmark)

Videbæk Le, Jette; Hansen, Helle P; Riisgaard, Helle

2015-01-01

BACKGROUND: Clinical guidelines are considered to be essential for improving quality and safety of health care. However, interventions to promote implementation of guidelines have demonstrated only partial effectiveness and the reasons for this apparent failure are not yet fully understood....... OBJECTIVE: To investigate how GPs implement clinical guidelines in everyday clinical practice and how implementation approaches differ between practices. METHODS: Individual semi-structured open-ended interviews with seven GPs who were purposefully sampled with regard to gender, age and practice form....... Interviews were recorded, transcribed verbatim and then analysed using systematic text condensation. RESULTS: Analysis of the interviews revealed three different approaches to the implementation of guidelines in clinical practice. In some practices the GPs prioritized time and resources on collective...

Clinical Trials

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Full Text Available ... Some companies and groups sponsor clinical trials that test the safety of products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ...

Clinical Research

DEFF Research Database (Denmark)

Christensen, Irene

2016-01-01

This paper is about the logic of problem solving and the production of scientific knowledge through the utilisation of clinical research perspective. Ramp-up effectiveness, productivity, efficiency and organizational excellence are topics that continue to engage research and will continue doing so...... for years to come. This paper seeks to provide insights into ramp-up management studies through providing an agenda for conducting collaborative clinical research and extend this area by proposing how clinical research could be designed and executed in the Ramp- up management setting....

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Full Text Available ... more information about eligibility criteria, go to "How Do Clinical Trials Work?" Some trials enroll people who ... for adults. For more information, go to "How Do Clinical Trials Protect Participants?" For more information about ...

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Full Text Available ... sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, ... and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually ...

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Clinical simulation training improves the clinical performance of Chinese medical students

Directory of Open Access Journals (Sweden)

Ming-ya Zhang

2015-10-01

Full Text Available Background: Modern medical education promotes medical students’ clinical operating capacity rather than the mastery of theoretical knowledge. To accomplish this objective, clinical skill training using various simulations was introduced into medical education to cultivate creativity and develop the practical ability of students. However, quantitative analysis of the efficiency of clinical skill training with simulations is lacking. Methods: In the present study, we compared the mean scores of medical students (Jinan University who graduated in 2013 and 2014 on 16 stations between traditional training (control and simulative training groups. In addition, in a clinical skill competition, the objective structured clinical examination (OSCE scores of participating medical students trained using traditional and simulative training were compared. The data were statistically analyzed and qualitatively described. Results: The results revealed that simulative training could significantly enhance the graduate score of medical students compared with the control. The OSCE scores of participating medical students in the clinical skill competition, trained using simulations, were dramatically higher than those of students trained through traditional methods, and we also observed that the OSCE marks were significantly increased for the same participant after simulative training for the clinical skill competition. Conclusions: Taken together, these data indicate that clinical skill training with a variety of simulations could substantially promote the clinical performance of medical students and optimize the resources used for medical education, although a precise analysis of each specialization is needed in the future.

Clinical expectations: what facilitators expect from ESL students on clinical placement.

Science.gov (United States)

San Miguel, Caroline; Rogan, Fran

2012-03-01

Many nursing students for whom English is a second language (ESL) face challenges related to communication on clinical placement and although clinical facilitators are not usually trained language assessors, they are often in a position of needing to assess ESL students' clinical language performance. Little is known, however, about the particular areas of clinical performance facilitators focus on when they are assessing ESL students. This paper discusses the results of a study of facilitators' written assessment comments about the clinical performance of a small group of ESL nursing students over a two and a half year period. These comments were documented on students' clinical assessment forms at the end of each placement. The results provide a more detailed insight into facilitators' expectations of students' language performance and the particular challenges faced by ESL students and indicate that facilitators have clear expectations of ESL students regarding communication, learning styles and professional demeanour. These findings may help both ESL students and their facilitators better prepare for clinical placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Full Text Available ... treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ... are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and ...

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Full Text Available ... go to the NHLBI's Children and Clinical Studies Web page. Children and Clinical Studies Learn more about ... Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees ...

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Full Text Available ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers ( ...

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

Science.gov (United States)

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

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Full Text Available ... Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ... and advance medical care. They also can help health care decisionmakers direct resources to the strategies and treatments ...

Clinical PET application

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Lim, Sang Moo; Hong, Song W.; Choi, Chang W.; Yang, Seong Dae [Korea Cancer Center Hospital, Seoul (Korea)

1997-12-01

PET gives various methabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 250 cases of PET images were obtained, which resulted total income of 180,000,000 won. 50,000,000 won was deposited for the 1998 PET clinical research. Second year PET clinical research should be managed under unified project. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18}FDG in a day purchase of HPLC pump and {sup 68}Ga pin source which was delayed due to economic crisis, should be done early in 1998. (author). 2 figs., 3 tabs.

Clinical Views: Object-Oriented Views for Clinical Databases

Science.gov (United States)

Portoni, Luisa; Combi, Carlo; Pinciroli, Francesco

1998-01-01

We present here a prototype of a clinical information system for the archiving and the management of multimedia and temporally-oriented clinical data related to PTCA patients. The system is based on an object-oriented DBMS and supports multiple views and view schemas on patients' data. Remote data access is supported too.

Clinical judgement within the South African clinical nursing environment: A concept analysis

Directory of Open Access Journals (Sweden)

Anna C. van Graan

2016-12-01

The findings emphasized clinical judgement as skill within the clinical nursing environment, thereby improving autonomous and accountable nursing care. These findings will assist nurse leaders and clinical nurse educators in developing a teaching-learning strategy to promote clinical judgement in undergraduate nursing students, thereby contributing to the quality of nursing care.

Clinical Trials

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Full Text Available ... the clinical trial you take part in, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because ...

Clinical outcomes in clinical trials of anti-HIV treatment

DEFF Research Database (Denmark)

Reekie, J; Mocroft, A; J, Neaton

2007-01-01

Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

Clinical research informatics

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Richesson, Rachel L

2012-01-01

This book provides foundational coverage of key areas, concepts, constructs, and approaches of medical informatics as it applies to clinical research activities, in both current settings and in light of emerging policies. The field of clinical research is fully characterized (in terms of study design and overarching business processes), and there is emphasis on information management aspects and informatics implications (including needed activities) within various clinical research environments. The purpose of the book is to provide an overview of clinical research (types), activities, and are

Hypothyroidism in clinical practice

Directory of Open Access Journals (Sweden)

Faiza Qari

2014-01-01

Full Text Available Background: Hypothyroidism is the most common endocrine disease that was seen in the clinical practice especially for family physicians. Methods: This review article covered the important practical clinical issues for managing overt hypothyroidism, subclinical hypothyroidism and hypothyroidism during pregnancy. Conclusions: The clinical issues were addressed by clinical scenario followed by questions and stressed on the important clinical points.

Clinical proteomics

DEFF Research Database (Denmark)

Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

2018-01-01

Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

Cognitive development, clinical knowledge, and clinical experience related to diagnostic ability.

Science.gov (United States)

Aquilino, M L

1997-01-01

To examine the relationship among cognitive development, clinical knowledge, and clinical experience in nursing students. A survey of junior and senior baccalaureate nursing students from three Midwestern colleges (N = 55). Students' diagnostic ability increased as they gained clinical experience and clinical knowledge. However, students failed to identify many nursing diagnoses and demonstrated only moderate levels of cognitive development. Nurse educators and nursing students need to change their approaches to teaching and learning to enhance students' diagnostic ability and cognitive development.

Clinical Trials

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Full Text Available ... Wide Range of Audiences The Children and Clinical Studies Program has been successfully developed and evaluated to fill an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, ...

Clinical microbiology informatics.

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Rhoads, Daniel D; Sintchenko, Vitali; Rauch, Carol A; Pantanowitz, Liron

2014-10-01

The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Detecting clinically relevant new information in clinical notes across specialties and settings.

Science.gov (United States)

Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

2017-07-05

Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

Clinical Trials

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Full Text Available ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, talk with your doctor. He or she may know about studies going on in your area. You can visit the following website to learn more about ...

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Full Text Available ... Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ... phase II clinical trials. The risk of side effects might be even greater for ... treatments. Health insurance and health care providers don't always ...

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Full Text Available ... more screening tests to see which test produces the best results. Some companies and groups sponsor clinical trials that test the ... and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

Quality improvement in clinical documentation: does clinical governance work?

Directory of Open Access Journals (Sweden)

Dehghan M

2013-12-01

Full Text Available Mahlegha Dehghan,1 Dorsa Dehghan,2 Akbar Sheikhrabori,3 Masoume Sadeghi,4 Mehrdad Jalalian5 1Department of Medical Surgical Nursing, School of Nursing and Midwifery, Kerman University of Medical Sciences, Kerman, 2Department of Pediatric Nursing, School of Nursing and Midwifery, Islamic Azad University Kerman Branch, Kerman, 3Department of Medical Surgical Nursing, School of Nursing and Midwifery, Kerman University of Medical Sciences, Kerman, 4Research Center for Modeling in Health, Institute of Futures Studies in Health, Kerman University of Medical Sciences, Kerman, 5Electronic Physician Journal, Mashhad, Iran Introduction: The quality of nursing documentation is still a challenge in the nursing profession and, thus, in the health care industry. One major quality improvement program is clinical governance, whose mission is to continuously improve the quality of patient care and overcome service quality problems. The aim of this study was to identify whether clinical governance improves the quality of nursing documentation. Methods: A quasi-experimental method was used to show nursing documentation quality improvement after a 2-year clinical governance implementation. Two hundred twenty random nursing documents were assessed structurally and by content using a valid and reliable researcher made checklist. Results: There were no differences between a nurse's demographic data before and after 2 years (P>0.05 and the nursing documentation score did not improve after a 2-year clinical governance program. Conclusion: Although some efforts were made to improve nursing documentation through clinical governance, these were not sufficient and more attempts are needed. Keywords: nursing documentation, clinical governance, quality improvement, nursing record

Treatment of clinical mastitis.

Science.gov (United States)

Roberson, Jerry R

2012-07-01

In summary, culture-based therapy and severity levels are key to management of clinical mastitis. Antibiotic therapy should be strongly considered for gram-positive clinical mastitis. Antibiotic therapy is not necessary for mild-to-moderate gram-negative clinical mastitis. Antibiotic therapy is warranted for practically all severe clinical mastitis as well as fluids and anti-inflammatory drugs. Clinical mastitis cases due to yeast and fungal pathogens or no growth isolates do not warrant antibiotic therapy.

Clinical Trials

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Full Text Available ... products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ... cancer also increased. As a result, the U.S. Food and Drug Administration now recommends never using HT ... Clinical Trials Work If you take ...

Cognitive performance in both clinical and non-clinical burnout

NARCIS (Netherlands)

Oosterholt, B.G.; Maes, J.H.R.; Linden, D. van der; Verbraak, M.J.P.M.; Kompier, M.A.J.

2014-01-01

Relatively little is known about cognitive performance in burnout. The aim of the present study was to further our knowledge on this topic by examining, in one study, cognitive performance in both clinical and non-clinical burnout while focusing on three interrelated aspects of cognitive

BOVINE PLASMA FIBRINOGEN AS MARKER IN CLINICAL AND SUB-CLINICAL MASTITIS

Directory of Open Access Journals (Sweden)

R. Ali

2018-06-01

Full Text Available Plasma samples were collected from healthy as well as clinical and sub-clinical mastitis affected cows from Barasat, West Bengal, India. Plasma samples, after ammonium sulphate precipitation, were dialyzed against several changes of PBS (pH 7.2 to remove the excess ammonium sulphate. Then plasma fibrinogens were purified by gel filtration chromatography on Sephacryl S-200 HR. SDS-PAGE (10% of purified fibrinogen from plasma of healthy cow revealed polypeptide bands of 74, 67 and 57 kDa which represent the α (alpha, β (beta and γ (gamma- chains respectively. On the other hand, purified fibrinogen from plasma of sub-clinical and clinical mastitis affected cow revealed polypeptide bands of 73 (α-chain, 68 kDa (β-chain and 72 (γ-chain, 68 kDa (β-chain respectively. The SDS-PAGE analysis showed the absence of gamma (γ- chain of fibrinogen in both the samples of sub-clinical and clinical mastitis positive cow. Single precipitin line was observed in double immunodiffusion test when purified fibrinogen from healthy, clinical and subclinical mastitis positive cows reacted with hyper immune sera raised in rabbit. No precipitin line was found against the normal control serum. These purified fibrinogens also showed cross reactivity against antibody raised in rabbit when analyzed by western blot technique.

Acceptance of clinical decision support surveillance technology in the clinical pharmacy.

Science.gov (United States)

English, Dan; Ankem, Kalyani; English, Kathleen

2017-03-01

There are clinical and economic benefits to incorporating clinical decision support systems (CDSSs) in patient care interventions in the clinical pharmacy setting. However, user dissatisfaction and resistance to HIT can prevent optimal use of such systems, particularly when users employ system workarounds and overrides. The present study applied a modified version of the unified theory of acceptance and use of technology (UTAUT) to evaluate the disposition and satisfaction with CDSS among clinical pharmacists who perform surveillance to identify potential medication therapy interventions on patients in the hospital setting. A survey of clinical pharmacists (N = 48) was conducted. Partial least squares (PLS) regression was used to analyze the influence of the UTAUT-related variables on behavioral intention and satisfaction with CDSS among clinical pharmacists. While behavioral intention did not predict actual use of HIT, facilitating conditions had a direct effect on pharmacists' use of CDSS. Likewise, satisfaction with CDSS was found to have a direct effect on use, with more satisfied users being less inclined to employ workarounds or overrides of the system. Based on the findings, organizational structures that facilitate CDSS use and user satisfaction affect the extent to which pharmacy and health care management maximize use in the clinical pharmacy setting.

59th Medical Wing Clinical Research Division Clinical Investigations Program Pathology Poster

Science.gov (United States)

2017-04-28

59 MDW/SGVU SUBJECT: Professional Presentation Approval 1. Your paper, entitled 59th Medical Wing Clinical Research Division Clinical Investigations...Program Pathology Poster presented at/published to For hanging in a hallway of the 591h Medical Wing Clinical Research Division, Bldg 4430 in...Graduate Health Sciences Education student and your department has told you they cannot fund your publication, the 59th Clinical Research Division may

Clinical Trials

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Full Text Available ... from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative ... safe a treatment is or how well it works. Children (aged 18 and younger) get ... legal consent for their child to take part in a clinical trial. When ...

Clinical Trials

Medline Plus

Full Text Available ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ... clinical trials are vital to the process of improving medical care. Many people ... participants, it may not work for you. A new treatment may have side ...

Evidence-based clinical practice

DEFF Research Database (Denmark)

Gluud, Christian

2002-01-01

, and single clinics. Accordingly, there is an urgent need to improve this situation. Guidelines for Good Clinical (Research) Practice, conduct of more trials as multicentre trials, The Consort Statement, and The Cochrane Collaboration may all help in the application of the best research evidence in clinical......Evidence-based medicine combines the patient's preferences with clinical experience and the best research evidence. Randomized clinical trials are considered the most valid research design for evaluating health-care interventions. However, empirical research shows that intervention effects may...... practice. By investments in education, applied research, and The Cochrane Collaboration, evidence-based medicine may form a stronger basis for clinical practice....

Attitudes of Pre-Clinical and Clinical Medical Students to Psychiatry ...

African Journals Online (AJOL)

Attitudes of Pre-Clinical and Clinical Medical Students to Psychiatry. ... Nigerian Hospital Practice ... Abstract. Medical training provides an environment in which proper and professional attitudes towards psychiatric patients can be acquired.

Variability in Clinical Integration Achieved by Athletic Training Students across Different Clinical Sport Assignments

Science.gov (United States)

Dodge, Thomas M.; Mazerolle, Stephanie M.; Bowman, Thomas G.

2015-01-01

Context: Clinical integration impacts athletic training students' (ATSs) motivation and persistence. Research has yet to elucidate the manner in which different clinical placements can influence clinical integration. Objective: To examine differences in the levels of clinical integration achieved by ATSs across various clinical sport assignments.…

Comparing the Effectiveness of a Clinical Registry and a Clinical Data Warehouse for Supporting Clinical Trial Recruitment: A Case Study

Science.gov (United States)

Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual

2010-01-01

This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost. PMID:21347102

Guide to clinical PET in oncology: Improving clinical management of cancer patients

International Nuclear Information System (INIS)

2008-10-01

Positron emission tomography (PET) has an approximately 50 year-history. It was developed as a tool of medical science to quantitatively measure metabolic rates of bio-substances in vivo and in particular the number of receptors in neuroscience. Until the late 1990s PET was, in most cases, research oriented activity. In 2001, positron emission tomography/X ray computed tomography (PET/CT) hybrid imaging system became commercially available. An era of clinical PET then emerged, in which PET images were utilized for clinical practice in the treatment and diagnosis of cancer patients. PET imaging could recognize areas of abnormal metabolic behaviour of cancers in vivo, and the addition of CT imaging underlines the site of malignancy. More accurate and precise interpretation of cancer lesions can therefore be performed by PET/CT imaging than PET or CT imaging alone. Clinical PET, in particular with fluorine-18-fluorodeoxyglucose ( 18 F-FDG), has already proven itself to have considerable value in oncology. The indications include malignant lymphoma and melanoma, head and neck cancers, oesophageal cancer, breast cancer, lung cancer and colorectal cancer, and it is still being expanded. The roles of clinical PET could be for 1) preoperative staging of cancers, 2) differentiation between residual tumour and scarring, 3) demonstration of suspected recurrences, 4) monitoring response to therapy, 5) prognosis and 6) radiotherapy treatment planning. Clinical PET can be used to illustrate exactly which treatment should be applied for a cancer patient as well as where surgeons should operate and where radiation oncologists should target radiation therapy. An almost exponential rise in the introduction of clinical PET, as well as the installation of PET/CT has been seen throughout the world. Clinical PET is currently viewed as the most powerful diagnostic tool in its field. This IAEA-TECDOC presents an overview of clinical PET for cancer patients and a relevant source of

Clinical review

DEFF Research Database (Denmark)

Groth, Kristian; Skakkebæk, Anne; Høst, Christian

2013-01-01

Recently, new clinically important information regarding Klinefelter syndrome (KS) has been published. We review aspects of epidemiology, endocrinology, metabolism, body composition, and neuropsychology with reference to recent genetic discoveries.......Recently, new clinically important information regarding Klinefelter syndrome (KS) has been published. We review aspects of epidemiology, endocrinology, metabolism, body composition, and neuropsychology with reference to recent genetic discoveries....

Report of a rare case of histiocytic necrotizing lymphadenitis with bilateral pleural effusion diagnosed via cervical lymph node biopsy

Directory of Open Access Journals (Sweden)

Xuchun Liu

2017-07-01

Full Text Available ABSTRACT CONTEXT: Histiocytic necrotizing lymphadenitis (HNL is a rare disorder that is often benign and self-limiting. There have been reports of co-occurrence of HNL with other diseases, including systemic lupus erythematosus, hemophagocytic syndrome and antiphospholipid syndrome. CASE REPORT: Here, we report a case in which a patient experienced unexplained fever, swelling of the cervical lymph node and bilateral pleural effusion and was ultimately diagnosed with HNL based on results from a lymph node biopsy. After treatment with glucocorticoid, the patient regained normal body temperature, the swelling of the lymph nodes disappeared and the pleural effusion was reabsorbed. CONCLUSIONS: The pathogenesis of HNL remains unclear, and pleural effusion is rarely reported in HNL patients. We presented this case to improve diagnostic awareness of this condition among clinicians and help reduce the likelihood of misdiagnosis.

Transforming RN education: clinical learning and clinical knowledge development.

Science.gov (United States)

Benner, P

1993-04-01

Transforming RN education has the potential for transforming clinical teaching and learning for all students. The returning RN student offers possibilities for clinical learning that the generic student does not have, but this should not cause us to limit the returning RN student to the generic level. Where possible innovative programs should be developed to move the RN student from baccalaureate level to the Master's level. As educators, we should take the opportunity to increase the numbers of nurses who are educationally prepared to move into advanced levels of practice. The returning RN student offers a rich human resource for the profession, and a rich resource for improving our clinical teaching as well as our practice.

Fertility Clinic Success Rates

Science.gov (United States)

... Defects ART and Autism 2013 Assisted Reproductive Technology Fertility Clinic Success Rates Report Recommend on Facebook Tweet ... Additional Information About ART in the United States. Fertility Clinic Tables Introduction to Fertility Clinic Tables [PDF - ...

Clinical dosimetry

International Nuclear Information System (INIS)

Rassow, J.

1973-01-01

The main point of this paper on clinical dosimetry which is to be understood here as application of physical dosimetry on accelerators in medical practice, is based on dosimetric methodics. Following an explanation of the dose parameters and description of the dose distribution important for clinical practice as well as geometric irradiation parameters, the significance of a series of physical parameters such as accelerator energy, surface energy of average stopping power etc. is dealt with in detail. Following a section on field homogenization with bremsstrahlung and electron radiation, details on dosimetry in clinical practice are given. Finally, a few problems of dosemeter or monitor calibration on accelerators are described. The explanations are supplemented by a series of diagrams and tables. (ORU/LH) [de

Clinical trial methodology

National Research Council Canada - National Science Library

Peace, Karl E; Chen, Ding-Geng

2011-01-01

"Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide...

NIH Clinical Centers

Data.gov (United States)

Federal Laboratory Consortium — The NIH Clinical Center consists of two main facilities: The Mark O. Hatfield Clinical Research Center, which opened in 2005, houses inpatient units, day hospitals,...

The Relationship between Clinical Competence and Clinical Self-efficacy among Nursing and Midwifery Students

Directory of Open Access Journals (Sweden)

Shahla Mohamadirizi

2015-12-01

Full Text Available Introduction  Self-efficacy in clinical performance had an important role in applying competencies; also competencies and self-efficacy in clinical performance influenced to quality care of nursing and midwifery students. So the present study aimed to define the relationship between clinical competencies and clinical self-efficacy among nursing and midwifery students. Materials and Methods  This is a cross-sectional study conducted on 150 of nursing and midwifery students in Isfahan University of Medical Science, selected through two stage sampling in 2014. The participant completed questionnaires about personal/ educational characteristics and nursing competencies questionnaire (18 items and clinical self-efficacy scale (37 items. The data were analyzed by, Pearson statistical test, t-test, variance analysis through SPSS version16. Results The results showed that 50% (n=75 and 37.4% (n=56 of nursing and midwifery students had good clinical competence and clinical Self-Efficacy, respectively. Also the mean competencies and self-efficacy in clinical performance scores were 35.05± 1.2 and 76.03± 0.4 respectively. Pearson correlation coefficient showed that there was a positive linear correlation between the score of clinical competence and clinical self-efficacy (P

Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice.

Science.gov (United States)

Hajjaj, F M; Salek, M S; Basra, M K A; Finlay, A Y

2010-05-01

This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine.

Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

Science.gov (United States)

Gillespie, Mary

2010-11-01

Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Clinical judgement within the South African clinical nursing environment: A concept analysis

Directory of Open Access Journals (Sweden)

Anna C. van Graan

2016-10-01

Full Text Available Reform in the South African healthcare and educational system were characterized by the ideals that the country needs to produce independent, critical thinkers. Nurses need to cope with diversity in a more creative way, defining their role in a complex, uncertain, rapidly changing health care environment. Quality clinical judgement is therefore imperative as an identified characteristic of newly qualified professional nurses. The objective of this study was to explore and describe clinical judgement through various data sources and review of literature to clarify the meaning and promote a common understanding through formulating the characteristics and developing a connotative (theoretical definition of the concept. An explorative, descriptive qualitative design was used to discover the complexity and meaning of the phenomenon. Multiple data sources and search strategies were used, for the time frame 1982—2013. A concept analysis was used to arrive at a theoretical definition of the concept of ‘clinical judgement’ as a complex cognitive skill to evaluate patient needs, adaption of current treatment protocols as well as new treatment strategies, prevention of adverse side effects through being proactive rather than reactive within the clinical nursing environment. The findings emphasized clinical judgement as skill within the clinical nursing environment, thereby improving autonomous and accountable nursing care. These findings will assist nurse leaders and clinical nurse educators in developing a teaching-learning strategy to promote clinical judgement in undergraduate nursing students, thereby contributing to the quality of nursing care.

Nursing students' clinical competencies: a survey on clinical education objectives.

Science.gov (United States)

Arrigoni, C; Grugnetti, A M; Caruso, R; Gallotti, M L; Borrelli, P; Puci, M

2017-01-01

Developing clearly defined competencies and identifying strategies for their measurement remain unfortunately a critical aspect of nursing training. In the current international context, which continues to be characterised by deep economic crisis, universities have a fundamental role to play in redefining the educational goals to respond to the expectations of certain geographical areas of interest, as underscored in the Bologna Process (Joint Declaration of the European Ministers of Education Convened in Bologna 19 June 1999). The aim of this observational study was to examine the clinical learning context of nursing students using a tool developed by a team of teachers for the analysis of clinical learning. Redefinition of the clinical learning objectives with reference to the competencies set out in the questionnaire validated by Venturini et al. (2012) and the subsequent use of the tool created by the team of teachers for students in the first, second and third-year courses of the 2013/14 academic year, covering all the internships called for in those years. All nursing students enrolled in the first, second and third year of the nursing undergraduate degree program at the University of Pavia (no. 471) participated in this survey. A total of 1,758 clinical internships were carried out: 461 for the first year, 471 for the second year and 826 for the third year. Setting objectives, beginning with the educational offerings in the several clinical contexts, represents a strong point for this process. The results highlight a level of heterogeneity and complexity intrinsic to the University of Pavia educational system, characterized by clinical settings with different clinical levels (Research hospital and other traditional hospitals) that offering different levels of training. The use of the self-evaluation form for clinical learning made it possible to perform real-time observations of the training activities of the entire student body. An educational model

Clinical review: Riedel's thyroiditis: a clinical review.

Science.gov (United States)

Hennessey, James V

2011-10-01

Riedel's thyroiditis is a rare inflammatory process involving the thyroid and surrounding cervical tissues and is associated with various forms of systemic fibrosis. Riedel's presentation is complex, including a thyroid mass associated with local symptoms, characteristic biochemical abnormalities such as hypocalcemia and hypothyroidism, as well as the involvement of a wide range of other organ systems. Diagnosis of Riedel's thyroiditis requires histopathological confirmation, but due to high complication rates, the role of surgical intervention is limited to airway decompression and diagnostic tissue retrieval. Unique among processes of the thyroid, Riedel's is commonly treated with long-term antiinflammatory medications to arrest progression and maintain a symptom-free course. Due to its rarity, Riedel's may not be immediately diagnosed, so clinicians benefit from recognizing the constellation of findings that should make prompt diagnosis possible. A review of print and electronic reviews was conducted. Source references were identified, and available literature was reviewed. A search of the PubMed database using the search term "Riedel's thyroiditis" was cross-referenced with associated clinical findings, systemic fibrosis diagnoses, and therapeutic search terms. Because most of the literature consisted of case reports and very small series, inclusion of identified articles was based on clinical descriptions of the subjects included and the criteria for diagnosis reported. More weight was attributed to series, using contemporary criteria for diagnosis. Case reports were included if the diagnosis was clear and clinical presentation was unique to illustrate the spectrum of disease. Because the majority of therapeutic intervention data were based upon case reports and very small series, an evidence-based approach was problematic, but information is presented as objectively and with as much balance as the limited quality of the data allows. Clinical awareness of the

Evaluating the MEDLINE Core Clinical Journals filter: data-driven evidence assessing clinical utility.

Science.gov (United States)

Klein-Fedyshin, Michele; Ketchum, Andrea M; Arnold, Robert M; Fedyshin, Peter J

2014-12-01

MEDLINE offers the Core Clinical Journals filter to limit to clinically useful journals. To determine its effectiveness for searching and patient-centric decision making, this study compared literature used for Morning Report in Internal Medicine with journals in the filter. An EndNote library with references answering 327 patient-related questions during Morning Report from 2007 to 2012 was exported to a file listing variables including designated Core Clinical Journal, Impact Factor, date used and medical subject. Bradford's law of scattering was applied ranking the journals and reflecting their clinical utility. Recall (sensitivity) and precision of the Core Morning Report journals and non-Core set was calculated. This study applied bibliometrics to compare the 628 articles used against these criteria to determine journals impacting decision making. Analysis shows 30% of clinically used articles are from the Core Clinical Journals filter and 16% of the journals represented are Core titles. When Bradford-ranked, 55% of the top 20 journals are Core. Articles sources used. Among the 63 Morning Report subjects, 55 have <50% precision and 41 have <50% recall including 37 subjects with 0% precision and 0% recall. Low usage of publications within the Core Clinical Journals filter indicates less relevance for hospital-based care. The divergence from high-impact medicine titles suggests clinically valuable journals differ from academically important titles. With few subjects demonstrating high recall or precision, the MEDLINE Core Clinical Journals filter may require a review and update to better align with current clinical needs. © 2014 John Wiley & Sons, Ltd.

Clinical reasoning: concept analysis.

Science.gov (United States)

Simmons, Barbara

2010-05-01

This paper is a report of a concept analysis of clinical reasoning in nursing. Clinical reasoning is an ambiguous term that is often used synonymously with decision-making and clinical judgment. Clinical reasoning has not been clearly defined in the literature. Healthcare settings are increasingly filled with uncertainty, risk and complexity due to increased patient acuity, multiple comorbidities, and enhanced use of technology, all of which require clinical reasoning. Data sources. Literature for this concept analysis was retrieved from several databases, including CINAHL, PubMed, PsycINFO, ERIC and OvidMEDLINE, for the years 1980 to 2008. Rodgers's evolutionary method of concept analysis was used because of its applicability to concepts that are still evolving. Multiple terms have been used synonymously to describe the thinking skills that nurses use. Research in the past 20 years has elucidated differences among these terms and identified the cognitive processes that precede judgment and decision-making. Our concept analysis defines one of these terms, 'clinical reasoning,' as a complex process that uses cognition, metacognition, and discipline-specific knowledge to gather and analyse patient information, evaluate its significance, and weigh alternative actions. This concept analysis provides a middle-range descriptive theory of clinical reasoning in nursing that helps clarify meaning and gives direction for future research. Appropriate instruments to operationalize the concept need to be developed. Research is needed to identify additional variables that have an impact on clinical reasoning and what are the consequences of clinical reasoning in specific situations.

ACCP Clinical Pharmacist Competencies.

Science.gov (United States)

Saseen, Joseph J; Ripley, Toni L; Bondi, Deborah; Burke, John M; Cohen, Lawrence J; McBane, Sarah; McConnell, Karen J; Sackey, Bryan; Sanoski, Cynthia; Simonyan, Anahit; Taylor, Jodi; Vande Griend, Joseph P

2017-05-01

The purpose of the American College of Clinical Pharmacy (ACCP) is to advance human health by extending the frontiers of clinical pharmacy. Consistent with this mission and its core values, ACCP is committed to ensuring that clinical pharmacists possess the knowledge, skills, attitudes, and behaviors necessary to deliver comprehensive medication management (CMM) in team-based, direct patient care environments. These components form the basis for the core competencies of a clinical pharmacist and reflect the competencies of other direct patient care providers. This paper is an update to a previous ACCP document and includes the expectation that clinical pharmacists be competent in six essential domains: direct patient care, pharmacotherapy knowledge, systems-based care and population health, communication, professionalism, and continuing professional development. Although these domains align with the competencies of physician providers, they are specifically designed to better reflect the clinical pharmacy expertise required to provide CMM in patient-centered, team-based settings. Clinical pharmacists must be prepared to complete the education and training needed to achieve these competencies and must commit to ongoing efforts to maintain competence through ongoing professional development. Collaboration among stakeholders will be needed to ensure that these competencies guide clinical pharmacists' professional development and evaluation by educational institutions, postgraduate training programs, professional societies, and employers. © 2017 Pharmacotherapy Publications, Inc.

Reorganizing the General Clinical Research Center to improve the clinical and translational research enterprise.

Science.gov (United States)

Allen, David; Ripley, Elizabeth; Coe, Antoinette; Clore, John

2013-12-01

In 2010, Virginia Commonwealth University (VCU) was granted a Clinical and Translational Science Award which prompted reorganization and expansion of their clinical research infrastructure. A case study approach is used to describe the implementation of a business and cost recovery model for clinical and translational research and the transformation of VCU's General Clinical Research Center and Clinical Trials Office to a combined Clinical Research Services entity. We outline the use of a Plan, Do, Study, Act cycle that facilitated a thoughtful transition process, which included the identification of required changes and cost recovery processes for implementation. Through this process, the VCU Center for Clinical and Translational Research improved efficiency, increased revenue recovered, reduced costs, and brought a high level of fiscal responsibility through financial reporting.

Discharge planning in a cardiology out-patient clinic: a clinical audit.

Science.gov (United States)

Ingram, Shirley; Khan, Barkat

2014-01-01

The purpose of this paper is to audit the active discharge (DC) planning process in a general cardiology clinic, by pre-assessing patients' medical notes and highlighting those suitable for potential DC to the clinic physician. The cardiology clinical nurse specialist (CNS) identified patients' for nine- to 12-month return visits one week prior to attendance. The previous consultation letter was accessed and information was documented by the CNS in the medical record. The key performance indicator (KPI) used was patient DCs for each clinic visit. The process was audited at three separate times to reflect recommended action carried out. The CNS pre-assessment and presence at the clinics significantly increased total DCs during the first period compared to usual care, 11 vs 34 per cent (p audit period, DCs fell (9 per cent) with a reduction in CNS pre-assessed DCs (10 per cent). Recommendations were implemented. The process was continued by clinic administration staff, colour coding all nine- to 12-month returns, resulted in a 19 per cent DC rate in 2012. CNS pre-assessment and highlighting DC suitability increased the number of patient DCs. As the CNS presence at the clinic reduced so did the rate of DC. Specific personnel need to be responsible for monitoring and reminding staff of the process; this does not always have to be medical or nursing. Implementing positive discharging procedures is aimed at improving quality, increasing efficiency and accessibility of services for patients. This audit describes a process to promote DC planning from cardiology outpatients.

Transforming practice into clinical scholarship.

Science.gov (United States)

Limoges, Jacqueline; Acorn, Sonia

2016-04-01

The aims of this paper were to explicate clinical scholarship as synonymous with the scholarship of application and to explore the evolution of scholarly practice to clinical scholarship. Boyer contributed an expanded view of scholarship that recognized various approaches to knowledge production beyond pure research (discovery) to include the scholarship of integration, application and teaching. There is growing interest in using Boyer's framework to advance knowledge production in nursing but the discussion of clinical scholarship in relation to Boyer's framework is sparse. Discussion paper. Literature from 1983-2015 and Boyer's framework. When clinical scholarship is viewed as a synonym for Boyer's scholarship of application, it can be aligned to this well established framework to support knowledge generated in clinical practice. For instance, applying the three criteria for scholarship (documentation, peer review and dissemination) can ensure that the knowledge produced is rigorous, available for critique and used by others to advance nursing practice and patient care. Understanding the differences between scholarly practice and clinical scholarship can promote the development of clinical scholarship. Supporting clinical leaders to identify issues confronting nursing practice can enable scholarly practice to be transformed into clinical scholarship. Expanding the understanding of clinical scholarship and linking it to Boyer's scholarship of application can assist nurses to generate knowledge that addresses clinical concerns. Further dialogue about how clinical scholarship can address the theory-practice gap and how publication of clinical scholarship could be expanded given the goals of clinical scholarship is warranted. © 2016 John Wiley & Sons Ltd.

Designing for Anxiety Therapy, Bridging Clinical and Non-Clinical

DEFF Research Database (Denmark)

Bertelsen, Olav Wedege; Kramp, Gunnar

2012-01-01

In this position paper we discuss, in terms of the concept of boundary objects, how a mobile application, the MIKAT.app, bridge between clinical intervention in anxiety therapy, and life and coping strategies outside the clinic and across phases of being a person suffering from, or having suffered...... from anxiety. Thereby, we hope to provide a counterpoint in the discussion on illness trajectories....

Use of an Objective Clinical Examination to Determine Clinical Competence.

Science.gov (United States)

Dupras, Denise M.; Li, James T. C.

1995-01-01

A study investigated performance of 51 second-year internal medicine residents on an objective structured clinical examination and analyzed the test's role in evaluating clinical competence. The examination included nine physical diagnoses and several test-interpretation stations. Performance was analyzed statistically and correlated with…

Transforming clinical practice guidelines and clinical pathways into fast-and-frugal decision trees to improve clinical care strategies.

Science.gov (United States)

Djulbegovic, Benjamin; Hozo, Iztok; Dale, William

2018-02-27

Contemporary delivery of health care is inappropriate in many ways, largely due to suboptimal Q5 decision-making. A typical approach to improve practitioners' decision-making is to develop evidence-based clinical practice guidelines (CPG) by guidelines panels, who are instructed to use their judgments to derive practice recommendations. However, mechanisms for the formulation of guideline judgments remains a "black-box" operation-a process with defined inputs and outputs but without sufficient knowledge of its internal workings. Increased explicitness and transparency in the process can be achieved by implementing CPG as clinical pathways (CPs) (also known as clinical algorithms or flow-charts). However, clinical recommendations thus derived are typically ad hoc and developed by experts in a theory-free environment. As any recommendation can be right (true positive or negative), or wrong (false positive or negative), the lack of theoretical structure precludes the quantitative assessment of the management strategies recommended by CPGs/CPs. To realize the full potential of CPGs/CPs, they need to be placed on more solid theoretical grounds. We believe this potential can be best realized by converting CPGs/CPs within the heuristic theory of decision-making, often implemented as fast-and-frugal (FFT) decision trees. This is possible because FFT heuristic strategy of decision-making can be linked to signal detection theory, evidence accumulation theory, and a threshold model of decision-making, which, in turn, allows quantitative analysis of the accuracy of clinical management strategies. Fast-and-frugal provides a simple and transparent, yet solid and robust, methodological framework connecting decision science to clinical care, a sorely needed missing link between CPGs/CPs and patient outcomes. We therefore advocate that all guidelines panels express their recommendations as CPs, which in turn should be converted into FFTs to guide clinical care. © 2018 John Wiley

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

Science.gov (United States)

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p research coordination and management" (p clinical practice.

Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation.

Science.gov (United States)

Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

2018-06-04

Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

Clinical implementation of pharmacogenetics.

Science.gov (United States)

García-González, Xandra; Cabaleiro, Teresa; Herrero, María José; McLeod, Howard; López-Fernández, Luis A

2016-03-01

In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not been as fast as desirable. The current situation of clinical implementation of pharmacogenetics is discussed. This review focuses on the advances of pharmacogenomics to individualize cancer treatments, the relationship between pharmacogenetics and pharmacodynamics in the clinical course of transplant patients receiving a combination of immunosuppressive therapy, the needs and barriers facing pharmacogenetic clinical application, and the situation of pharmacogenetic testing in Spain. It is based on lectures presented by speakers of the Clinical Implementation of Pharmacogenetics Symposium at the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held in April 20, 2015.

Importance of training on clinical thinking and clinical competence to interventional radiologists

International Nuclear Information System (INIS)

Xu Ke; Zhong Hongshan

2010-01-01

Although the history of Interventional Radiology is no longer than 50 years, interventional techniques have been dramatically developed. Interventional radiologists have been responsible for much of the medical innovations and development of the minimally invasive procedures that are commonplace today to treat many complicated diseases as physicians. But the education backgrounds of interventional radiologist in China are different. Therefore, we should be aware that the job of an interventional radiologist is totally different from that of a diagnostic radiologist. It is very important to train interventional radiologists for improving their clinical thinking and clinical competence. Herein, we propose our suggestions on how to improve the clinical thinking and clinical competence of interventional radiologists. In this paper we also systemically introduce the accurate and proper treatment procedures which should be strictly followed in clinical work and,meanwhile, the perioperative patients care is emphasized. (authors)

Varieties of clinical reasoning.

Science.gov (United States)

Bolton, Jonathan W

2015-06-01

Clinical reasoning comprises a variety of different modes of inference. The modes that are practiced will be influenced by the sociological characteristics of the clinical settings and the tasks to be performed by the clinician. This article presents C.S. Peirce's typology of modes of inference: deduction, induction and abduction. It describes their differences and their roles as stages in scientific argument. The article applies the typology to reasoning in clinical settings. The article describes their differences, and their roles as stages in scientific argument. It then applies the typology to reasoning in typical clinical settings. Abduction is less commonly taught or discussed than induction and deduction. However, it is a common mode of inference in clinical settings, especially when the clinician must try to make sense of a surprising phenomenon. Whether abduction is followed up with deductive and inductive verification is strongly influenced by situational constraints and the cognitive and psychological stamina of the clinician. Recognizing the inevitability of abduction in clinical practice and its value to discovery is important to an accurate understanding of clinical reasoning. © 2015 John Wiley & Sons, Ltd.

American Association for Clinical Chemistry

Science.gov (United States)

... Find the answer to your question IN CLINICAL CHEMISTRY Hs-cTnI as a Gatekeeper for Further Cardiac ... Online Harmonization.net Commission on Accreditation in Clinical Chemistry American Board of Clinical Chemistry Clinical Chemistry Trainee ...

Fundamentals of clinical trials

CERN Document Server

Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B

2015-01-01

This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise.  Most chapters have been revised considerably from the fourth edition.  A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded.  Many contemporary clinical trial examples have been added.  There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials.  This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...

Conducting clinical trials in Singapore.

Science.gov (United States)

Woo, K T

1999-04-01

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Characteristics of student preparedness for clinical learning: clinical educator perspectives using the Delphi approach

Directory of Open Access Journals (Sweden)

Chipchase Lucinda S

2012-11-01

Full Text Available Abstract Background During clinical placements, clinical educators facilitate student learning. Previous research has defined the skills, attitudes and practices that pertain to an ideal clinical educator. However, less attention has been paid to the role of student readiness in terms of foundational knowledge and attitudes at the commencement of practice education. Therefore, the aim of this study was to ascertain clinical educators’ views on the characteristics that they perceive demonstrate that a student is well prepared for clinical learning. Methods A two round on-line Delphi study was conducted. The first questionnaire was emailed to a total of 636 expert clinical educators from the disciplines of occupational therapy, physiotherapy and speech pathology. Expert clinical educators were asked to describe the key characteristics that indicate a student is prepared for a clinical placement and ready to learn. Open-ended responses received from the first round were subject to a thematic analysis and resulted in six themes with 62 characteristics. In the second round, participants were asked to rate each characteristic on a 7 point Likert Scale. Results A total of 258 (40.56% responded to the first round of the Delphi survey while 161 clinical educators completed the second (62.40% retention rate. Consensus was reached on 57 characteristics (six themes using a cut off of greater than 70% positive respondents and an interquartile deviation IQD of equal or less than 1. Conclusions This study identified 57 characteristics (six themes perceived by clinical educators as indicators of a student who is prepared and ready for clinical learning. A list of characteristics relating to behaviours has been compiled and could be provided to students to aid their preparation for clinical learning and to universities to incorporate within curricula. In addition, the list provides a platform for discussions by professional bodies about the role of placement

Clinical governance and external audit.

Science.gov (United States)

Glazebrook, S G; Buchanan, J G

2001-01-01

This paper describes a model of clinical governance that was developed at South Auckland Health during the period 1995 to 2000. Clinical quality and safety are core objectives. A multidisciplinary Clinical Board is responsible for the development and publicising of sound clinical policies together with monitoring the effects of their implementation on quality and safety. The Clinical Board has several committees, including an organization-wide Continuous Quality Improvement Committee to enhance the explicit nature of the quality system in terms of structure, staff awareness and involvement, and to develop the internal audit system. The second stream stems from the Chief Medical Officer and clinical directors in a clinical management sense. The Audit Committee of the Board of Directors covers both clinical and financial audit. The reporting lines back to that committee are described and the role of the external auditor of clinical standards is explained. The aim has been to create a supportive culture where quality initiatives and innovation can flourish, and where the emphasis is not on censure but improvement.

Clinical image quality evaluation for panoramic radiography in Korean dental clinics

International Nuclear Information System (INIS)

Choi, Bo Ram; Choi, Da Hye; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Choi, Soon Chul; Bae, Kwang Hak; Lee, Sam Sun

2012-01-01

The purpose of this study was to investigate the level of clinical image quality of panoramic radiographs and to analyze the parameters that influence the overall image quality. Korean dental clinics were asked to provide three randomly selected panoramic radiographs. An oral and maxillofacial radiology specialist evaluated those images using our self-developed Clinical Image Quality Evaluation Chart. Three evaluators classified the overall image quality of the panoramic radiographs and evaluated the causes of imaging errors. A total of 297 panoramic radiographs were collected from 99 dental hospitals and clinics. The mean of the scores according to the Clinical Image Quality Evaluation Chart was 79.9. In the classification of the overall image quality, 17 images were deemed 'optimal for obtaining diagnostic information,' 153 were 'adequate for diagnosis,' 109 were 'poor but diagnosable,' and nine were 'unrecognizable and too poor for diagnosis'. The results of the analysis of the causes of the errors in all the images are as follows: 139 errors in the positioning, 135 in the processing, 50 from the radiographic unit, and 13 due to anatomic abnormality. Panoramic radiographs taken at local dental clinics generally have a normal or higher-level image quality. Principal factors affecting image quality were positioning of the patient and image density, sharpness, and contrast. Therefore, when images are taken, the patient position should be adjusted with great care. Also, standardizing objective criteria of image density, sharpness, and contrast is required to evaluate image quality effectively.

Site Characteristics Influencing the Translation of Clinical Research Into Clinical Practice

DEFF Research Database (Denmark)

Smed, Marie; Getz, Kenneth A.

2014-01-01

Investigative sites participating in clinical trials play an instrumental role in aiding market adoption. Site experiences in clinical research help physician investigators and research professionals gain familiarity with and exposure to investigational treatments. This knowledge may be passed...

Learning for clinical leadership.

Science.gov (United States)

Cook, Michael J; Leathard, Helen L

2004-11-01

Clinical leadership has been acclaimed widely as a major factor influencing the quality of patient care but research has revealed a paucity of preparation for this significant role. Leadership literature has rarely addressed clinical leadership specifically or referred to the difficulties in characterizing effective clinical leaders. The research informing this paper focused on clinical leadership and identified five attributes of effective clinical leaders: creativity, highlighting, influencing, respecting, and supporting. Effective clinical leaders adopted a transformational leadership style and improved care, through others, by including transformational (soft) knowledge as an integral part of their effective practice repertoire. Phronesis is introduced as practical wisdom that is gained through immersion in relevant experience, and as an essential element of preparation for clinical nursing leadership practice. It is argued, that learning to transform care requires opportunities to work within an environment that engenders and supports aspiring leaders. The paper describes the research process, elucidates the attributes through illustrative examples from the research data, and discusses an emergent educational strategy for the development of these attributes by clinicians in their practice environments. The paper also describes the application of this research through an interdisciplinary programme for staff leading teams in both health and social services sectors.

Clinical outcomes in clinical trials of anti-HIV treatment

DEFF Research Database (Denmark)

Reekie, J; Mocroft, A; J, Neaton

2007-01-01

Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

The educational and professional status of clinical embryology and clinical embryologists in Europe.

Science.gov (United States)

Kovačič, B; Plas, C; Woodward, B J; Verheyen, G; Prados, F J; Hreinsson, J; De los Santos, M J; Magli, M C; Lundin, K; Plancha, C E

2015-08-01

What is the recognition of clinical embryology and the current status of clinical embryologists in European countries, regarding educational levels, responsibilities and workload, and need for a formal education in assisted reproductive technology (ART)? It is striking that the profession of clinical embryology, almost 40 years after the introduction of IVF, is still not officially recognized in most European countries. Reproductive medicine has developed into a sophisticated multidisciplinary medical branch since the birth of Louise Brown 37 years ago. The European Board & College of Obstetrics and Gynaecology (EBCOG) has recognized reproductive medicine as a subspeciality and has developed a subspeciality training for gynaecologists in collaboration with the European Society for Human Reproduction and Embryology (ESHRE). However, nothing similar exists for the field of clinical embryology or for clinical embryologists. A questionnaire about the situation in clinical embryology in the period of 2012-2013 in the respective European country was sent to ESHRE National representatives (basic scientists only) in December 2013. At this time, 28 European countries had at least one basic scientist in the ESHRE Committee of National Representatives. The survey consisted of 46 numeric, dichotomous (yes/no) or descriptive questions. Answers were obtained from 27 out of 28 countries and the data were tabulated. Data about the numbers of 'ESHRE Certified Embryologists' were taken from the ESHRE Steering Committee for Embryologist Certification. In 2012, more than 7000 laboratory staff from 1349 IVF clinics in 27 European countries performed over 700 000 fresh and frozen ART cycles. Despite this, clinical embryology is only recognized as an official profession in 3 out of 27 national health systems. In most countries clinical embryologists need to be registered under another profession, and have limited possibilities for organized education in clinical embryology. Mostly they

Developing Clinical Competence

NARCIS (Netherlands)

P.F. Wimmers (Paul)

2006-01-01

textabstractThe development of clinical competence is the main purpose of medical education. The long road to become clinically competent starts on the first day of medical school, and every institution strives to select the best students. The responsibility of medical schools is to train

Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice

OpenAIRE

Hajjaj, FM; Salek, MS; Basra, MKA; Finlay, AY

2010-01-01

This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional co...

Tools in a clinical information system supporting clinical trials at a Swiss University Hospital.

Science.gov (United States)

Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg

2014-12-01

Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of

Clinical diagnostic ultrasound

International Nuclear Information System (INIS)

Barnett, E.; Morley, P.

1986-01-01

This textbook on diagnostic ultrasound covers the main systems, with emphasis being placed on the clinical application of diagnostic ultrasound in everyday practice. It provides not only a textbook for postgraduates (particularly FRCR candidates), but also a reference work for practitioners of clinical ultrasound and clinicians generally

Clinical leadership project.

Science.gov (United States)

Kling, Vera G

2010-11-01

Nurse educators seek innovative strategies to maximize student learning in the classroom and clinical settings. Students enrolled in a nursing leadership and management course often find they spend more clinical time observing leaders than practicing the necessary skills to lead others in the provision of nursing care. In addition, opportunities to explore the nurse educator role often do not exist in baccalaureate nursing education, despite the shortage of nurse educators. An experience was developed in a baccalaureate nursing program to give senior students, under supervision of faculty, the opportunity to lead and evaluate lower-level students providing patient care in the clinical setting and to experience the role of nursing faculty. Feedback from senior students was positive, and students noted increased proficiency in leadership ability and critical thinking. Student interest in the nurse educator role was also enhanced. Program expansion and evaluation with faculty, clinical staff, and patients are planned. Copyright 2010, SLACK Incorporated.

[Future roles of clinical laboratories and clinical laboratory technologists in university hospitals].

Science.gov (United States)

Yokota, Hiromitsu; Yatomi, Yutaka

2013-08-01

Clinical laboratories in university hospitals should be operated with a good balance of medical practice, education, research, and management. The role of a clinical laboratory is to promptly provide highly reliable laboratory data to satisfy the needs of clinicians involved in medical practice and health maintenance of patients. Improvement and maintenance of the quality of the laboratory staff and environment are essential to achieve this goal. In order to implement these requirements efficiently, an appropriate quality management system should be introduced and established, and evaluated objectively by a third party (e.g. by obtaining ISO 15189 certification). ISO 15189 is an international standard regarding the quality and competence of clinical laboratories, and specifies a review of the efficient operational system and technical requirements such as competence in implementing practical tests and calibration. This means the results of laboratory tests reported by accredited laboratories withstand any international evaluation, which is very important to assure the future importance of the existence and management of clinical laboratories as well as internationalization of medical practice. "Education" and "research" have important implications in addition to "medical practice" and "management", as the roles that clinical laboratories should play in university hospitals. University hospital laboratories should be operated by keeping these four factors in good balance. Why are "education" and "research" required in addition to "medical practice" services? If individual clinical laboratory technologists can provide an appropriate response to this question, the importance of the existence of clinical laboratories would be reinforced, without being compromised.

Clinical image quality evaluation for panoramic radiography in Korean dental clinics

Energy Technology Data Exchange (ETDEWEB)

Choi, Bo Ram; Choi, Da Hye; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Choi, Soon Chul; Bae, Kwang Hak; Lee, Sam Sun [School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

2012-09-15

The purpose of this study was to investigate the level of clinical image quality of panoramic radiographs and to analyze the parameters that influence the overall image quality. Korean dental clinics were asked to provide three randomly selected panoramic radiographs. An oral and maxillofacial radiology specialist evaluated those images using our self-developed Clinical Image Quality Evaluation Chart. Three evaluators classified the overall image quality of the panoramic radiographs and evaluated the causes of imaging errors. A total of 297 panoramic radiographs were collected from 99 dental hospitals and clinics. The mean of the scores according to the Clinical Image Quality Evaluation Chart was 79.9. In the classification of the overall image quality, 17 images were deemed 'optimal for obtaining diagnostic information,' 153 were 'adequate for diagnosis,' 109 were 'poor but diagnosable,' and nine were 'unrecognizable and too poor for diagnosis'. The results of the analysis of the causes of the errors in all the images are as follows: 139 errors in the positioning, 135 in the processing, 50 from the radiographic unit, and 13 due to anatomic abnormality. Panoramic radiographs taken at local dental clinics generally have a normal or higher-level image quality. Principal factors affecting image quality were positioning of the patient and image density, sharpness, and contrast. Therefore, when images are taken, the patient position should be adjusted with great care. Also, standardizing objective criteria of image density, sharpness, and contrast is required to evaluate image quality effectively.

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

Science.gov (United States)

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Recognition of clinical deterioration: a clinical leadership opportunity for nurse executive.

Science.gov (United States)

Swartz, Colleen

2013-01-01

Recognition and avoidance of further clinical deterioration can be termed a critical success factor in every care delivery model. As care resources become more constrained and allocated to the most critical of patients, some patients are being shifted to less intense and costly care settings where continuous physiologic monitoring may not be an option. Nurse executives are facing these complex issues as they work with clinical experts to develop systems of safety in the patient care arena. A systematic review of the literature related to the recognition of clinical deterioration is needed to identify areas for further leadership, research, and practice advancements.

Clinical supervisors' perceived needs for teaching communication skills in clinical practice.

Science.gov (United States)

Perron, N Junod; Sommer, J; Hudelson, P; Demaurex, F; Luthy, C; Louis-Simonet, M; Nendaz, M; De Grave, W; Dolmans, D; van der Vleuten, C P M

2009-07-01

Lack of faculty training is often cited as the main obstacle to post-graduate teaching in communication skills. To explore clinical supervisors' needs and perceptions regarding their role as communication skills trainers. Four focus group discussions were conducted with clinical supervisors from two in-patient and one out-patient medical services from the Geneva University Hospitals. Focus groups were audio taped, transcribed verbatim and analyzed in a thematic way using Maxqda software for qualitative data analysis. Clinical supervisors said that they frequently addressed communication issues with residents but tended to intervene as rescuers, clinicians or coaches rather than as formal instructors. They felt their own training did not prepare them to teach communication skills. Other barriers to teach communication skills include lack of time, competing demands, lack of interest and experience on the part of residents, and lack of institutional priority given to communication issues. Respondents expressed a desire for experiential and reflective training in a work-based setting and emphasised the need for a non-judgmental learning atmosphere. Results suggest that organisational priorities, culture and climate strongly influence the degree to which clinical supervisors may feel comfortable to teach communication skills to residents. Attention must be given to these contextual factors in the development of an effective communication skills teaching program for clinical supervisors.

Clinical Outcomes Used in Clinical Pharmacy Intervention Studies in Secondary Care

Directory of Open Access Journals (Sweden)

Lene Juel Kjeldsen

2017-05-01

Full Text Available The objective was to investigate type, frequency and result of clinical outcomes used in studies to assess the effect of clinical pharmacy interventions in inpatient care. The literature search using Pubmed.gov was performed for the period up to 2013 using the search phrases: “Intervention(s” and “pharmacist(s” and “controlled” and “outcome(s” or “effect(s”. Primary research studies in English of controlled, clinical pharmacy intervention studies, including outcome evaluation, were selected. Titles, abstracts and full-text papers were assessed individually by two reviewers, and inclusion was determined by consensus. In total, 37 publications were included in the review. The publications presented similar intervention elements but differed in study design. A large variety of outcome measures (135 had been used to evaluate the effect of the interventions; most frequently clinical measures/assessments by physician and health care service use. No apparent pattern was established among primary outcome measures with significant effect in favour of the intervention, but positive effect was most frequently related to studies that included power calculations and sufficient inclusion of patients (73% vs. 25%. This review emphasizes the importance of considering the relevance of outcomes selected to assess clinical pharmacy interventions and the importance of conducting a proper power calculation.

Danish clinical databases: An overview

DEFF Research Database (Denmark)

Green, Anders

2011-01-01

Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark.......Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark....

4 pitfalls to clinical integration.

Science.gov (United States)

Redding, John

2012-11-01

Four common mistakes can easily thwart clinical integration: Assuming that EHR adoption is the cornerstone of successful integration; Delaying the development of ambulatory services that support clinical integration; Believing that knowledge of clinical integration initiatives will passively diffuse through the ranks; Attaching too much weight to Federal Trade Commission/Department of Justice approval of a clinical integration model.

Clinical Data Warehousing - A Survey

DEFF Research Database (Denmark)

Pedersen, Torben Bach; Jensen, Christian Søndergaard

1998-01-01

In this article we present the concept of data warehousing, and its use in the clinical area. Clinical data warehousing will become very important in the near future, as healthcare enterprises need to gain more information from their clinical, administrative, and financial data, in order to impro...... in the area, and providing criteria for comparing clinical data warehouse systems....

Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

Science.gov (United States)

Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

2015-01-01

The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

A descriptive survey investigating pre-registration student nurses' perceptions of clinical skill development in clinical placements.

Science.gov (United States)

Stayt, Louise C; Merriman, Clair

2013-04-01

Clinical skill development is essential to nurse education. Clinical skills are frequently taught in higher education institutions using clinical simulation. It is unclear if clinical skills are subsequently consolidated and developed in clinical placements. The aim of this survey was to evaluate pre-registration student nurses perceptions of the frequency of opportunities to practise, the level of supervision and assessment of, clinical skills in their clinical placements. This was a cross-sectional survey design using an online, self-report questionnaire including a Likert-type scale and open ended comments. Four hundred and twenty one students, from all year groups, from a university in the south of England on a wide variety of clinical placements participated. Participants evaluated the frequency of opportunity to practise, level of supervision and assessment of and feedback on performance of specific clinical skills. Clinical skills evaluated were measurement of vital signs, aseptic non-touch technique, assisting with eating and drinking, and assisting with comfort and hygiene. Data were analysed utilising Statistical Package for the Social Sciences Version 19. The frequency of opportunities to practise skills in clinical placement was variable with some participants reporting that they never had opportunity to practise essential skills. Similarly the level of supervision and assessment was also inconsistent suggesting that participants frequently practised clinical skills unsupervised without being assessed as competent. Inconsistencies in clinical skill development may lead to graduates who are not work ready and as a result, insufficient clinical competence potentially leads to unsafe practice and poor patient care. This calls for stronger partnerships between educators and clinical areas and the prioritisation of mentor preparation and education as well as organisational support in terms of mentor workload planning. Copyright © 2012 Elsevier Ltd. All

New insights into how trafficking regulates T cell receptor signaling

Directory of Open Access Journals (Sweden)

Jieqiong Lou

2016-07-01

Full Text Available AbstractThere is emerging evidence that exocytosis plays an important role in regulating T cell receptor (TCR signaling. The trafficking molecules involved in lytic granule (LG secretion in cytotoxic T lymphocytes (CTL have been well studied due to the immune disorder known as familial hemophagocytic lymphohisiocytosis (FHLH. However, the knowledge of trafficking machineries regulating the exocytosis of receptors and signaling molecules remains quite limited. In this review, we summarize the reported trafficking molecules involved in the transport of the TCR and downstream signaling molecules to the cell surface. By combining this information with the known knowledge of LG exocytosis and general exocytic trafficking machinery, we attempt to draw a more complete picture of how the TCR signaling network and exocytic trafficking matrix are interconnected to facilitate T cell activation. This also highlights how membrane compartmentalization facilitates the spatiotemporal organization of cellular responses that are essential for immune functions.

Future requirements. Clinical investigations

DEFF Research Database (Denmark)

Qvist, V.

2002-01-01

Biocompatability, Cariology, Clinical trials, Dental materials, Helath services research, Human, Pedodontics......Biocompatability, Cariology, Clinical trials, Dental materials, Helath services research, Human, Pedodontics...

Effect of Objective Structured Clinical Examination on Nursing Students' Clinical Skills

Directory of Open Access Journals (Sweden)

Seyedeh Narjes Mousavizadeh

2018-01-01

Full Text Available Considering the daily increasing changes in clinical training approaches, the necessity of using new evaluation methods in proportion with these approaches is also becoming more and more obvious for measuring all of the cognitive, emotional and psychomotor dimensions of students. The present study was designed and conducted for reviewing the effect of objective structured clinical examination method on the clinical skills of nursing students. In this quasi-experimental study, 48 nursing students have participated that were randomly assigned to two groups of intervention and control. The intervention group students were evaluated at the end of educational period of their clinical skills and principles course using objective structured clinical examination (OSCE. The OSCE included five core skills in this course: assessing and fulfilling patients’ basic needs, dressing up, injectable drug therapy, noninjectable drug therapy, infection control. The control group students were evaluated using the routine method. Both groups of students were followed up in the next semester and were compared in terms of learning enhancement in these five skills. Evaluation of procedures was based on valid and reliable check-lists made by the researcher. Results were analyzed using descriptive and inferential statistics (Chi-square, independent and paired T tests. The mean score of the final evaluation in the intervention group was significantly higher than that of the control group (P= 0.000. Final evaluation scores of the intervention group students showed a better performance than their previous semester (P= 0.000, while the final evaluation scores of the control group students showed a lack of progress in their skills (P<0.05. It seems that this evaluation method also is a support for students' learning and resulted in improvement of clinical skills among them. Accordingly, it is recommended that nursing education centers apply this method to assess students�

Using systematically observed clinical encounters (SOCEs to assess medical students’ skills in clinical settings

Directory of Open Access Journals (Sweden)

George R Bergus

2010-11-01

Full Text Available George R Bergus1–3, Jerold C Woodhead4, Clarence D Kreiter2,51Performance Based Assessment Program, Office of Student Affairs and Curriculum, 2Department of Family Medicine, 3Department of Psychiatry, 4Department of Pediatrics, 5Office of Consultation and Research in Medical Education, Roy J and Lucille A Carver College of Medicine, The University of Iowa, Iowa City, IA, USAIntroduction: The Objective Structured Clinical Examination (OSCE is widely used to assess the clinical performance of medical students. However, concerns related to cost, availability, and validity, have led educators to investigate alternatives to the OSCE. Some alternatives involve assessing students while they provide care to patients – the mini-CEX (mini-Clinical Evaluation Exercise and the Long Case are examples. We investigated the psychometrics of systematically observed clinical encounters (SOCEs, in which physicians are supplemented by lay trained observers, as a means of assessing the clinical performances of medical students.Methods: During the pediatrics clerkship at the University of Iowa, trained lay observers assessed the communication skills of third-year medical students using a communication checklist while the students interviewed and examined pediatric patients. Students then verbally presented their findings to faculty, who assessed students’ clinical skills using a standardized form. The reliability of the combined communication and clinical skills scores was calculated using generalizability theory.Results: Fifty-one medical students completed 199 observed patient encounters. The mean combined clinical and communication skills score (out of a maximum 45 points was 40.8 (standard deviation 3.3. The calculated reliability of the SOCE scores, using generalizability theory, from 10 observed patient encounters was 0.81. Students reported receiving helpful feedback from faculty after 97% of their observed clinical encounters.Conclusion: The SOCE can

Brucellosis in Kosovo and Clinical Features of Brucellosis at University clinical center of Kosovo

OpenAIRE

Buçaj, Emine; Puca, Edmond; Namani, Sadie; Bajrami, Muharem; Krasniqi, Valbon; Berisha, Lindita; Jakupi, Xhevat; Halili, Bahrie; Kraja, Dhimiter

2015-01-01

Objective: Brucellosis became a remarkable disease in Kosovo. But there is not a comprehensive epidemiological study about pidemiology and clinical course of this disease from Kosovo. The aim of our study is to present demographic and clinical data of patients with brucellosis at University Clinical Center of Kosovo.Methods: A retrospective study was performed for the patients with brucellosis treated in our clinic during years 2011- 2012. The data about demography, history of the disease, cl...

Demystifying the reflective clinical journal

International Nuclear Information System (INIS)

Milinkovic, Danielle; Field, Nikki

2005-01-01

Student learning on clinical placement is a complex issue and cannot be defined solely by just doing things. Reflection during clinical practice is essential if the student is going to learn from the experience. Therefore it is important for educators to include as part of clinical education programs learning strategies that encourage reflection. The reflective clinical journal is an educational tool that is employed by the School of Medical Radiation Sciences at the University of Sydney to encourage reflection of undergraduate radiation therapy students whilst on clinical placement. This discussion paper explores the key concepts of reflection and the reflective clinical journal. Due to the paucity of information about this issue in radiation therapy the literature reviewed is from across all areas of the health sciences

Clinical physiology grand rounds.

Science.gov (United States)

Richards, Jeremy; Schwartzstein, Richard; Irish, Julie; Almeida, Jacqueline; Roberts, David

2013-04-01

Clinical Physiology Grand Rounds (CPGR) is an interactive, case-based conference for medical students designed to: (1) integrate preclinical and clinical learning; (2) promote inductive clinical reasoning; and (3) emphasise students as peer teachers. CPGR specifically encourages mixed learning level student interactions and emphasises the use of concept mapping. We describe the theoretical basis and logistical considerations for an interactive, integrative, mixed-learner environment such as CPGR. In addition, we report qualitative data regarding students' attitudes towards and perceptions of CPGR. Medical students from first to fourth year participate in a monthly, interactive conference. The CPGR was designed to bridge gaps and reinforce linkages between basic science and clinical concepts, and to incorporate interactive vertical integration between preclinical and clinical students. Medical education and content experts use Socratic, interactive teaching methods to develop real-time concept maps to emphasise the presence and importance of linkages across curricula. Student focus groups were held to assess attitudes towards and perceptions of the mixed-learner environment and concept maps in CPGR. Qualitative analyses of focus group transcripts were performed to develop themes and codes describing the students' impressions of CPGR. CPGR is a case-based, interactive conference designed to help students gain an increased appreciation of linkages between basic science and clinical medicine concepts, and an increased awareness of clinical reasoning thought processes. Success is dependent upon explicit attention being given to goals for students' integrated learning. © Blackwell Publishing Ltd 2013.

Financial and clinical governance implications of clinical coding accuracy in neurosurgery: a multidisciplinary audit.

Science.gov (United States)

Haliasos, N; Rezajooi, K; O'neill, K S; Van Dellen, J; Hudovsky, Anita; Nouraei, Sar

2010-04-01

Clinical coding is the translation of documented clinical activities during an admission to a codified language. Healthcare Resource Groupings (HRGs) are derived from coding data and are used to calculate payment to hospitals in England, Wales and Scotland and to conduct national audit and benchmarking exercises. Coding is an error-prone process and an understanding of its accuracy within neurosurgery is critical for financial, organizational and clinical governance purposes. We undertook a multidisciplinary audit of neurosurgical clinical coding accuracy. Neurosurgeons trained in coding assessed the accuracy of 386 patient episodes. Where clinicians felt a coding error was present, the case was discussed with an experienced clinical coder. Concordance between the initial coder-only clinical coding and the final clinician-coder multidisciplinary coding was assessed. At least one coding error occurred in 71/386 patients (18.4%). There were 36 diagnosis and 93 procedure errors and in 40 cases, the initial HRG changed (10.4%). Financially, this translated to pound111 revenue-loss per patient episode and projected to pound171,452 of annual loss to the department. 85% of all coding errors were due to accumulation of coding changes that occurred only once in the whole data set. Neurosurgical clinical coding is error-prone. This is financially disadvantageous and with the coding data being the source of comparisons within and between departments, coding inaccuracies paint a distorted picture of departmental activity and subspecialism in audit and benchmarking. Clinical engagement improves accuracy and is encouraged within a clinical governance framework.

Students' Assessment and Self-assessment of Nursing Clinical Faculty Competencies: Important Feedback in Clinical Education?

Science.gov (United States)

Lovrić, Robert; Prlić, Nada; Zec, Davor; Pušeljić, Silvija; Žvanut, Boštjan

2015-01-01

The students' assessment of clinical faculty competencies and the faculty members' self-assessment can provide important information about nursing clinical education. The aim of this study was to identify the differences between the students' assessment of the clinical faculty member's competencies and the faculty member's self-assessment. These differences can reveal interesting insights relevant for improving clinical practice.

Social media in clinical trials.

Science.gov (United States)

Thompson, Michael A

2014-01-01

Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

Science.gov (United States)

Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

2013-01-01

Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; pdisintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

Ophthalmology patients' interest in online access to clinic notes at three US clinics.

Science.gov (United States)

Lee, Bryan S; Oster, Natalia V; Chen, Galen Y; Ding, Leona L; Walker, Janice D; Elmore, Joann G

2017-07-01

This study aimed to understand patients' perceptions about potential benefits and harms of accessing their own ophthalmology clinic notes via an electronic patient portal as part of the OpenNotes initiative. The authors conducted a cross-sectional, in-person survey of ophthalmology patients at three US eye clinics. The paper survey was self-administered or administered with assistance from study staff before or after patients' clinical visits. The authors used descriptive statistics to summarise patient characteristics and patient attitudes about accessing their ophthalmology notes online. Chi-square and t-tests were performed to assess differences in patient responses between clinic locations. Four hundred and fifty-one patients responded (response rate 65%). Most patients thought that accessing doctors' notes online was a good idea (95%), wanted to view their clinic notes online (94%), and agreed online access would increase their understanding of their eye problems (95%) and help them better remember their care plan (94%); 14% said online access would increase their worry; 43% had privacy concerns; and 96% indicated they would show or discuss their notes with at least one other person. Non-white patients were more likely than white patients to perceive online clinic notes as a useful tool, but they were also more likely to worry and to express greater privacy concerns. Patients at three US eye clinics were strongly in favour of online access to ophthalmology notes and were optimistic this access would improve their understanding and self-care. Ophthalmologists should consider offering online access to their notes to enhance doctor-patient communication and improve clinical outcomes. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

[Clinical pharmacy and surgery: Review].

Science.gov (United States)

Jarfaut, A; Nivoix, Y; Vigouroux, D; Kehrli, P; Gaudias, J; Kempf, J-F; Levêque, D; Gourieux, B

2014-05-01

Clinical pharmacy has been developed and evaluated in various medical hospital activities. Reviews conducted in this area reported a higher value of this discipline. In surgical services, evenly adverse drug events may occur, so clinical pharmacy activities must also help to optimize the management of drug's patient. The objectives of this literature review is to determine the profile of clinical pharmacy activities developed in surgical services and identify indicators. The research was conducted on Pubmed(®) database with the following keywords (2000-2013), "surgery", "pharmacy", "pharmacist", "pharmaceutical care", "impact" and limited to French or English papers. Studies dealing on simultaneously medical and surgical areas were excluded. Twenty-one papers were selected. The most frequently developed clinical pharmacy activities were history and therapeutic drug monitoring (antibiotics or anticoagulants). Two types of indicators were identified: activity indicators with the number of pharmaceutical interventions, their description and clinical signification, the acceptance rate and workload. Impact indicators were mostly clinical and economic impacts. The development of clinical pharmacy related to surgical patients is documented and appears to have, as for medical patients, a clinical and economical value. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

Science.gov (United States)

Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

2014-01-01

Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment.

Doctors and nurses on wards with greater access to clinical dietitians have better focus on clinical nutrition

DEFF Research Database (Denmark)

Thoresen, L.; Rothenberg, E.; Beck, Anne Marie

2008-01-01

According to the Council of Europe, clinical dietitians should assume a more central role in nutritional support. The aim of this study was to assess the opinions among doctors, nurses and clinical dietitians regarding the use of clinical dietitians' expertise in the hospital units and, further......, to assess whether the presence of clinical dietitians in hospital departments influenced doctors and nurses focus on clinical nutrition. A questionnaire about the use of clinical nutrition was mailed to 6000 doctors and 6000 nurses working in hospital units where undernutrition is documented to be common...... into the importance of adequate nutrition was better than those who saw clinical dietitians seldom. Clinical nutrition had a higher priority in units with frequent visits by clinical dietitians. The present study shows that doctors and nurses on wards with greater access to clinical dietitians had better focus...

Clinical audit of COPD in outpatient respiratory clinics in Spain: the EPOCONSUL study

Directory of Open Access Journals (Sweden)

Calle Rubio M

2017-01-01

Full Text Available Myriam Calle Rubio,1–3 Bernardino Alcázar Navarrete,4 Joan B Soriano,5 Juan J Soler-Cataluña,6 José Miguel Rodríguez González-Moro,7 Manuel E Fuentes Ferrer,2,3,8 José Luis López-Campos9 On behalf of the EPOCONSUL Study 1Pulmonary Department, Hospital Clínico San Carlos, 2Department of Medicine, Faculty of Medicine, University Complutense of Madrid, 3Research Institute of Hospital Clínico San Carlos (IdISSC, Madrid, 4Pulmonary Department, Hospital de Alta Resolución de Noja, Granada, 5Research Institute of Hospital University La Princesa (IISP, University Autónoma of Madrid, 6Pulmonary Department, Hospital de Arnau de Villanova, Valencia, 7Pulmonary Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Madrid, 8UGC of Preventive Medicine and Research Institute of Hospital Clínico San Carlos, Madrid, 9Pulmonary Department, Hospital University Virgen del Rocio, Institute of Biomedicine of Sevilla (IBiS, Sevilla, Spain Background: Chronic obstructive pulmonary disease (COPD outpatients account for a large burden of usual care by respirologists. EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics. We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.Methodology: This is an observational study with prospective recruitment (May 2014–May 2015 of patients with a COPD diagnosis as seen in outpatient respiratory clinics. The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.Results: A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated. Of the 5,726 patients selected, 4,508 (78.7% were eligible. Overall, 12.1% of COPD patients

A Clinical Evaluation of Definitive and Clinical Allergic Bronchopulmonary Mycosis

OpenAIRE

Matsuse, Hiroto; Nakata, Hiroko; Fukahori, Susumu; Tsuchida, Tomoko; Kawano, Tetsuya; Tomari, Shinya; Fukushima, Chizu; Matsuo, Nobuko; Asai, Sadahiro; Kohno, Shigeru

2006-01-01

Objective: The present study aims to overcome problems associated with the early diagnosis of allergic bronchopulmonary mycosis (ABPM) using the current criteria. Patients and Methods: Clinical features including radiographic findings from 10 patients with definitive ABPM based on the diagnostic criteria of Rosenberg-Patterson were compared with those from 9 patients with ABPM clinically diagnosed by respiratory allergy specialists. Results: ABPM should be considered in patients with peripher...

Use of an Objective Structured Clinical Examination in Clinical Nurse Specialist Education.

Science.gov (United States)

Cuevas, Heather E; Timmerman, Gayle M

2016-01-01

Helping patients maximize their potential using expert coaching to facilitate lifestyle change is an important practice area for clinical nurse specialists (CNSs). The purpose is to determine the usefulness of objective structured clinical examinations (OSCEs) for evaluating CNS students' coaching competencies in the context of facilitating lifestyle change. Despite the use of OSCEs to assess competencies in clinical skills (eg, performance of procedures, decision making), its potential for evaluating coaching competencies for lifestyle change has not been demonstrated. We developed 4 OSCEs dealing with coaching patients in exercise, weight loss, stress reduction, or nonpharmacologic management of hyperlipidemia. Evaluation criteria included (1) approach to the patient, (2) information gathering, (3) motivational interviewing, and (4) management (medical and behavioral strategies). Student performance ranged from highly organized with proficient coaching skills to disorganized and focused solely on clinical management and prescriptive communication. Student responses were positive. Objective structured clinical examinations were highly useful for evaluating CNS students' coaching competencies for lifestyle change. Using OSCEs early in the semester to provide students feedback on their performance and again at the end to determine improvement optimizes use of this teaching strategy.

Clinical intuition versus statistics: different modes of tacit knowledge in clinical epidemiology and evidence-based medicine.

Science.gov (United States)

Braude, Hillel D

2009-01-01

Despite its phenomenal success since its inception in the early nineteen-nineties, the evidence-based medicine movement has not succeeded in shaking off an epistemological critique derived from the experiential or tacit dimensions of clinical reasoning about particular individuals. This critique claims that the evidence-based medicine model does not take account of tacit knowing as developed by the philosopher Michael Polanyi. However, the epistemology of evidence-based medicine is premised on the elimination of the tacit dimension from clinical judgment. This is demonstrated through analyzing the dichotomy between clinical and statistical intuition in evidence-based medicine's epistemology of clinical reasoning. I argue that clinical epidemiology presents a more nuanced epistemological model for the application of statistical epidemiology to the clinical context. Polanyi's theory of tacit knowing is compatible with the model of clinical reasoning associated with clinical epidemiology, but not evidence-based medicine.

Development of a clinical data warehouse from an intensive care clinical information system.

Science.gov (United States)

de Mul, Marleen; Alons, Peter; van der Velde, Peter; Konings, Ilse; Bakker, Jan; Hazelzet, Jan

2012-01-01

There are relatively few institutions that have developed clinical data warehouses, containing patient data from the point of care. Because of the various care practices, data types and definitions, and the perceived incompleteness of clinical information systems, the development of a clinical data warehouse is a challenge. In order to deal with managerial and clinical information needs, as well as educational and research aims that are important in the setting of a university hospital, Erasmus Medical Center Rotterdam, The Netherlands, developed a data warehouse incrementally. In this paper we report on the in-house development of an integral part of the data warehouse specifically for the intensive care units (ICU-DWH). It was modeled using Atos Origin Metadata Frame method. The paper describes the methodology, the development process and the content of the ICU-DWH, and discusses the need for (clinical) data warehouses in intensive care. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Research Areas - Clinical Trials

Science.gov (United States)

Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

Assessing student clinical learning experiences.

Science.gov (United States)

Nehyba, Katrine; Miller, Susan; Connaughton, Joanne; Singer, Barbara

2017-08-01

This article describes the use of an activity worksheet and questionnaire to investigate the learning experience of students on clinical placement. The worksheet measures the amount of time students spend in different learning activities, and the questionnaire explores student satisfaction and preferred learning activities. An activity worksheet and questionnaire … investigate[d] the learning experiences of students on clinical placement METHODS: The activity worksheet and questionnaire were used in a cohort pilot study of physiotherapy students on clinical placement. The activity worksheet provides details of the amount of time students engage in a range of clinical and non-clinical tasks while on placement, such as time spent treating patients, working individually, working with their peers and engaging in reflective practice. In combination with the questionnaire results, it allows clinicians to gain an understanding of the clinical learning environment experienced by their students. The data collected using these tools provide a description of the students' activities while undertaking the clinical placement. This information may guide the refinement of the clinical experience, and offers an opportunity to individualise learning activities to match students' needs and preferences. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Rewards and advancements for clinical pharmacists.

Science.gov (United States)

Goodwin, S Diane; Kane-Gill, Sandra L; Ng, Tien M H; Melroy, Joel T; Hess, Mary M; Tallian, Kimberly; Trujillo, Toby C; Vermeulen, Lee C

2010-01-01

The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient.

The clinical utility of the Maslach Burnout Inventory in a clinical population

NARCIS (Netherlands)

Kleijweg, J.H.M.; Verbraak, M.J.P.M.; Dijk, M.K. van

2013-01-01

This replication study examines the use of the Maslach Burnout Inventory (MBI-GS), a self-report questionnaire on burnout, as a clinical diagnostic instrument for measuring clinical burnout. The MBI and Mini International Neuropsychiatric Interview (MINI), a semistructured interview based on

Supporting Student Nurses Learning in and through Clinical Practice: The Role of the Clinical Guide.

Science.gov (United States)

Andrews, Margaret; Roberts, Debbie

2003-01-01

A clinical guide is an experienced nurse who supports nursing students throughout the program, particularly in clinical placements. More than a mentor, a guide is fully involved in promoting deep learning in clinical settings. (SK)

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

Science.gov (United States)

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

Fidelity in clinical simulation

DEFF Research Database (Denmark)

Jensen, Sanne; Nøhr, Christian; Rasmussen, Stine Loft

2013-01-01

Clinical simulation may be used to identify user needs for context sensitive functionalities in e-Health. The objective with this paper is to describe how user requirements and use cases in a large EHR-platform procurement may be validated by clinical simulation using a very low-fidelity prototype...... without any existing test data. Instead of using test scenarios and use cases, the healthcare professionals who are participating in the clinical simulation are generating both scenario and patient data themselves. We found that this approach allows for an imaginative discussion, not restricted by known...... functionalities and limitations, of the ideal EHR-platform. Subsequently, we discuss benefits and challenges of using an extremely low fidelity environment and discuss the degree of fidelity necessary for conducting clinical simulation....

Changes in information behavior in clinical teams after introduction of a clinical librarian service

Science.gov (United States)

Urquhart, Christine; Turner, Janet; Durbin, Jane; Ryan, Jean

2007-01-01

Objectives: The eighteen-month evaluation of a clinical librarian project (October 2003–March 2005) conducted in North Wales, United Kingdom (UK) assessed the benefits of clinical librarian support to clinical teams, the impact of mediated searching services, and the effectiveness of information skills training, including journal club support. Methods: The evaluation assessed changes in teams' information-seeking behavior and their willingness to delegate searching to a clinical librarian. Baseline (n = 69 responses, 73% response rate) and final questionnaire (n = 57, 77% response rate) surveys were complemented by telephone and face-to-face interviews (n = 33) among 3 sites served. Those attending information skills training sessions (n = 130) completed evaluations at the session and were surveyed 1 month after training (n = 24 questionnaire responses, n = 12 interviews). Results: Health professionals in clinical teams reported that they were more willing to undertake their own searching, but also more willing to delegate some literature searching, than at the start of the project. The extent of change depended on the team and the type of information required. Information skills training was particularly effective when organized around journal clubs. Conclusions: Collaboration with a clinical librarian increased clinician willingness to seek information. Clinical librarian services should leverage structured training opportunities such as journal clubs. PMID:17252062

Perspectives on Clinical Informatics: Integrating Large-Scale Clinical, Genomic, and Health Information for Clinical Care

Directory of Open Access Journals (Sweden)

In Young Choi

2013-12-01

Full Text Available The advances in electronic medical records (EMRs and bioinformatics (BI represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

42 CFR 405.2452 - Services and supplies incident to clinical psychologist and clinical social worker services.

Science.gov (United States)

2010-10-01

... psychologist and clinical social worker services. 405.2452 Section 405.2452 Public Health CENTERS FOR MEDICARE... clinical social worker services. (a) Services and supplies incident to a clinical psychologist's or clinical social worker's services are reimbursable under this subpart if the service or supply is— (1) Of a...

Clinical multiphoton tomography and clinical two-photon microendoscopy

Science.gov (United States)

König, Karsten; Bückle, Rainer; Weinigel, Martin; Elsner, Peter; Kaatz, Martin

2009-02-01

We report on applications of high-resolution clinical multiphoton tomography based on the femtosecond laser system DermaInspectTM with its flexible mirror arm in Australia, Asia, and Europe. Applications include early detection of melanoma, in situ tracing of pharmacological and cosmetical compounds including ZnO nanoparticles in the epidermis and upper dermis, the determination of the skin aging index SAAID as well as the study of the effects of anti-aging products. In addition, first clinical studies with novel rigid high-NA two-photon 1.6 mm GRIN microendoscopes have been conducted to study the effect of wound healing in chronic wounds (ulcus ulcera) as well as to perform intrabody imaging with subcellular resolution in small animals.

The Ethics of Clinical Care and the Ethics of Clinical Research: Yin and Yang.

Science.gov (United States)

Kowalski, Charles J; Hutchinson, Raymond J; Mrdjenovich, Adam J

2017-02-01

The Belmont Report's distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Concept-Based Learning in Clinical Experiences: Bringing Theory to Clinical Education for Deep Learning.

Science.gov (United States)

Nielsen, Ann

2016-07-01

Concept-based learning is used increasingly in nursing education to support the organization, transfer, and retention of knowledge. Concept-based learning activities (CBLAs) have been used in clinical education to explore key aspects of the patient situation and principles of nursing care, without responsibility for total patient care. The nature of best practices in teaching and the resultant learning are not well understood. The purpose of this multiple-case study research was to explore and describe concept-based learning in the context of clinical education in inpatient settings. Four clinical groups (each a case) were observed while they used CBLAs in the clinical setting. Major findings include that concept-based learning fosters deep learning, connection of theory with practice, and clinical judgment. Strategies used to support learning, major teaching-learning foci, and preconditions for concept-based teaching and learning will be described. Concept-based learning is promising to support integration of theory with practice and clinical judgment through application experiences with patients. [J Nurs Educ. 2016;55(7):365-371.]. Copyright 2016, SLACK Incorporated.

Clinical dosimetry using mosfets

International Nuclear Information System (INIS)

Ramani, Ramaseshan; Russell, Stephen; O'Brien, Peter

1997-01-01

Purpose: The use of metal oxide-silicon field effect transistors (MOSFETs) as clinical dosimeters is demonstrated for a number of patients with targets at different clinical sites. Methods and Materials: Commercially available MOSFETs were characterized for energy response, angular dependency of response, and effect of accumulated dose on sensitivity and some inherent properties of MOSFETs. The doses determined both by thermoluminescence dosimetry (TLD) and MOSFETs in clinical situation were evaluated and compared to expected doses determined by calculation. Results: It was observed that a standard calibration of 0.01 Gy/mV gave MOSFET determined doses which agreed with expected doses to within 5% at the 95% confidence limit for photon beams from 6 to 25 MV and electron beams from 5 to 14 MeV. An energy-dependent variation in response of up to 28% was observed between two orientations of a MOSFET. The MOSFET doses compared very well with the doses estimated by TLDs, and the patients tolerated MOSFETs very well. A standard deviation of 3.9% between expected dose and MOSFET determined dose was observed, while for TLDs the standard deviation was 5.1%. The advantages and disadvantages of using MOSFETs for clinical dosimetry are discussed in detail. Conclusion: It was concluded that MOSFETs can be used as clinical dosimeters and can be a good alternative to TLDs. However, they have limitations under certain clinical situations

Clinical biochemistry education in Spain.

Science.gov (United States)

Queraltó, J M

1994-12-31

Clinical biochemistry in Spain was first established in 1978 as an independent specialty. It is one of several clinical laboratory sciences specialties, together with haematology, microbiology, immunology and general laboratory (Clinical analysis, análisis clinicos). Graduates in Medicine, Pharmacy, Chemistry and Biological Sciences can enter post-graduate training in Clinical Chemistry after a nation-wide examination. Training in an accredited Clinical Chemistry department is 4 years. A national committee for medical and pharmacist specialties advises the government on the number of trainees, program and educational units accreditation criteria. Technical staff includes nurses and specifically trained technologists. Accreditation of laboratories is developed at different regional levels. The Spanish Society for Clinical Biochemistry and Molecular Pathology (SECQ), the national representative in the IFCC, has 1600 members, currently publishes a scientific journal (Química Clinica) and a newsletter. It organizes a continuous education program, a quality control program and an annual Congress.

HISTIOCYTOSIS X: CLINICAL OBSERVATIONS

Directory of Open Access Journals (Sweden)

E. Y. Ponomareva

2012-01-01

Full Text Available Two clinical cases of pulmonary Langerhans cell histiocytosis X have been analyzed demonstrating lung and other inner organ pathology, common clinical and X-ray features but different life prognosis.

Clinical immunology - Autoimmunity in the Netherlands

NARCIS (Netherlands)

Tervaert, Jan Willem Cohen; Kallenberg, Cees G. M.

2014-01-01

Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking

Clinical and para-clinical tests in the routine examination of headache patients

DEFF Research Database (Denmark)

Friberg, L; Sandrini, G; Jänig, W

2000-01-01

Para-clinical examinations in the diagnosis and treatment control of headache patients vary considerably between clinics and headache centers. Among the neurological societies in Europe there has been a consensus that some common procedures and recommendations should be created. In the Fall of 19...

The changing landscape for clinical research.

Science.gov (United States)

Heinig, S J; Quon, A S; Meyer, R E; Korn, D

1999-06-01

The authors review the history of U.S. clinical research and identify the profound changes stemming from advancements in the biomedical sciences, the recent transformation in the organization and financing of health care delivery, and the increasing application of information technologies. They observe that the enterprise must reorganize to account for the changed landscape, but there is a lack of the data necessary to monitor change and determine the extent to which clinical research is successfully realigning and sustaining itself. The authors discuss the evolving definition, scope, and venues for clinical research, and review previous analyses of clinical research's difficulties and remedies proposed: shared responsibility in the financing of academic medicine, support by federal and private health insurers for routine costs of patient care in clinical trials, and strengthened collaboration between and among industry, academia, insurers, and government. The authors conclude by describing two major initiatives to foster clinical investigation in the new landscape. The first is the Clinical Research Summit Project, a convocation of representative stakeholders from the health care system with an interest in clinical research, whose charge will be to formulate a national agenda for clinical research that has the broad-based support of the stakeholders. Among the challenges of this undertaking are the needs to identify new and stable sources of support for clinical research infrastructure, assess the future workforce needs for clinical investigation, and devise new methods to ensure the continued vitality and account-ability of clinical research. The second is the Clinical Research Task Force, an initiative of the Association of American Medical Colleges (AAMC), which is already exploring and advising on how AAMC member organizations can best strengthen their capacity to support clinical research programs in the current scientific, health care delivery, and financial

Clinical Laboratory Fee Schedule

Data.gov (United States)

U.S. Department of Health & Human Services — Outpatient clinical laboratory services are paid based on a fee schedule in accordance with Section 1833(h) of the Social Security Act. The clinical laboratory fee...

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

Science.gov (United States)

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Beninese vaccination clinic

OpenAIRE

Linda Sun

2017-01-01

This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

Is a clinical sociolinguistics possible?

Science.gov (United States)

Ball, M J

1992-01-01

This paper considers the idea of developing a clinical sociolinguistics. Various areas of the field are examined, and the importance of the 'core' area of the correlation of non-linguistic variables with linguistic variables stressed. Issues concerning language and class, region, sex, age and context of utterance are investigated, together with the implications for clinical linguistics. Finally, the difficulty of integrating such issues into clinical assessment is explored, and a tentative step forward suggested along the lines of a 'clinical sociolinguistic checklist'.

Learning Clinical Procedures Through Internet Digital Objects: Experience of Undergraduate Students Across Clinical Faculties.

Science.gov (United States)

Li, Tse Yan; Gao, Xiaoli; Wong, Kin; Tse, Christine Shuk Kwan; Chan, Ying Yee

2015-04-14

Various digital learning objects (DLOs) are available via the World Wide Web, showing the flow of clinical procedures. It is unclear to what extent these freely accessible Internet DLOs facilitate or hamper students' acquisition of clinical competence. This study aimed to understand the experience of undergraduate students across clinical disciplines-medicine, dentistry, and nursing-in using openly accessible Internet DLOs, and to investigate the role of Internet DLOs in facilitating their clinical learning. Mid-year and final-year groups were selected from each undergraduate clinical degree program of the University of Hong Kong-Bachelor of Medicine and Bachelor of Surgery (MBBS), Bachelor of Dental Surgery (BDS), and Bachelor of Nursing (BNurs). All students were invited to complete a questionnaire on their personal and educational backgrounds, and their experiences and views on using Internet DLOs in learning clinical procedures. The questionnaire design was informed by the findings of six focus groups. Among 439 respondents, 97.5% (428/439) learned a variety of clinical procedures through Internet DLOs. Most nursing students (107/122, 87.7%) learned preventive measures through Internet DLOs, with a lower percentage of medical students (99/215, 46.0%) and dental students (43/96, 45%) having learned them this way (both Plearning in the planned curriculum. This trend calls for a transformation of the educator's role from dispensing knowledge to guidance and support.

77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

Science.gov (United States)

2012-08-16

... investigator initiated research. Topics for discussion include the following: (1) What FDA Expects in a...] Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...-sponsorship with the Society of Clinical Research Associates (SoCRA) is announcing a public workshop. The...

Clinical Databases for Chest Physicians.

Science.gov (United States)

Courtwright, Andrew M; Gabriel, Peter E

2018-04-01

A clinical database is a repository of patient medical and sociodemographic information focused on one or more specific health condition or exposure. Although clinical databases may be used for research purposes, their primary goal is to collect and track patient data for quality improvement, quality assurance, and/or actual clinical management. This article aims to provide an introduction and practical advice on the development of small-scale clinical databases for chest physicians and practice groups. Through example projects, we discuss the pros and cons of available technical platforms, including Microsoft Excel and Access, relational database management systems such as Oracle and PostgreSQL, and Research Electronic Data Capture. We consider approaches to deciding the base unit of data collection, creating consensus around variable definitions, and structuring routine clinical care to complement database aims. We conclude with an overview of regulatory and security considerations for clinical databases. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Radioimmunoassay in clinical practice

Energy Technology Data Exchange (ETDEWEB)

Ametov, A S

1982-01-01

A wide application of radioimmunoassay in clinical practice is shown. The main theoretical aspects of radioimmunoassay and the fields of application in clinical practice - endocrinology, oncology, allergology, cardiology, pharmacology, pediatrics, hematology, obstetrics and gynecology, are presented.

A magneto-motive ultrasound platform designed for pre-clinical and clinical applications

Directory of Open Access Journals (Sweden)

Diego Ronaldo Thomaz Sampaio

Full Text Available Abstract Introduction Magneto-motive ultrasound (MMUS combines magnetism and ultrasound (US to detect magnetic nanoparticles in soft tissues. One type of MMUS called shear-wave dispersion magneto-motive ultrasound (SDMMUS analyzes magnetically induced shear waves (SW to quantify the elasticity and viscosity of the medium. The lack of an established presets or protocols for pre-clinical and clinical studies currently limits the use of MMUS techniques in the clinical setting. Methods This paper proposes a platform to acquire, process, and analyze MMUS and SDMMUS data integrated with a clinical ultrasound equipment. For this purpose, we developed an easy-to-use graphical user interface, written in C++/Qt4, to create an MMUS pulse sequence and collect the ultrasonic data. We designed a graphic interface written in MATLAB to process, display, and analyze the MMUS images. To exemplify how useful the platform is, we conducted two experiments, namely (i MMUS imaging to detect magnetic particles in the stomach of a rat, and (ii SDMMUS to estimate the viscoelasticity of a tissue-mimicking phantom containing a spherical target of ferrite. Results The developed software proved to be an easy-to-use platform to automate the acquisition of MMUS/SDMMUS data and image processing. In an in vivo experiment, the MMUS technique detected an area of 6.32 ± 1.32 mm2 where magnetic particles were heterogeneously distributed in the stomach of the rat. The SDMMUS method gave elasticity and viscosity values of 5.05 ± 0.18 kPa and 2.01 ± 0.09 Pa.s, respectively, for a tissue-mimicking phantom. Conclusion Implementation of an MMUS platform with addressed presets and protocols provides a step toward the clinical implementation of MMUS imaging equipment. This platform may help to localize magnetic particles and quantify the elasticity and viscosity of soft tissues, paving a way for its use in pre-clinical and clinical studies.

Assigning clinical codes with data-driven concept representation on Dutch clinical free text.

Science.gov (United States)

Scheurwegs, Elyne; Luyckx, Kim; Luyten, Léon; Goethals, Bart; Daelemans, Walter

2017-05-01

Clinical codes are used for public reporting purposes, are fundamental to determining public financing for hospitals, and form the basis for reimbursement claims to insurance providers. They are assigned to a patient stay to reflect the diagnosis and performed procedures during that stay. This paper aims to enrich algorithms for automated clinical coding by taking a data-driven approach and by using unsupervised and semi-supervised techniques for the extraction of multi-word expressions that convey a generalisable medical meaning (referred to as concepts). Several methods for extracting concepts from text are compared, two of which are constructed from a large unannotated corpus of clinical free text. A distributional semantic model (i.c. the word2vec skip-gram model) is used to generalize over concepts and retrieve relations between them. These methods are validated on three sets of patient stay data, in the disease areas of urology, cardiology, and gastroenterology. The datasets are in Dutch, which introduces a limitation on available concept definitions from expert-based ontologies (e.g. UMLS). The results show that when expert-based knowledge in ontologies is unavailable, concepts derived from raw clinical texts are a reliable alternative. Both concepts derived from raw clinical texts perform and concepts derived from expert-created dictionaries outperform a bag-of-words approach in clinical code assignment. Adding features based on tokens that appear in a semantically similar context has a positive influence for predicting diagnostic codes. Furthermore, the experiments indicate that a distributional semantics model can find relations between semantically related concepts in texts but also introduces erroneous and redundant relations, which can undermine clinical coding performance. Copyright © 2017. Published by Elsevier Inc.

Clinical and demographic trends in a sexually transmitted infection clinic in Mumbai (1994-2006): an epidemiologic analysis.

Science.gov (United States)

Setia, Maninder S; Jerajani, Hemangi R; Brassard, Paul; Boivin, Jean-Francois

2010-01-01

People presenting to sexually transmitted infections (STIs) clinics represent an important risk group for HIV infection; prevention strategies will depend on the clinical attendance. The demographic and clinical changes in clinic attendees in Mumbai, as well as the factors associated with HIV infection in this clinic over a 13-year period, were assessed. STI clinic data in 3417 individuals (1994 to 2006) were analyzed: clinical presentation, types of STIs, and serology over the 13-year period. We used a logistic regression model to assess socio-demographic and clinical associations with HIV infection. The clinic evaluated 689 patients in 1994 and the number had dropped to 97 in 2006. In 1994, the majority of STIs seen in the clinic were bacterial (53%, 95% confidence interval [CI] 50% to 57%); however, this proportion had dropped in 2006 (28%, 95% CI: 19% to 38%). There was a proportional increase in viral STIs during the same time period. Although women attending the clinic were younger than men, they were more likely to be married. The overall seropositivity for HIV was 28%. Viral STIs were more likely to be associated with HIV than bacterial infections (odds ratio: 1.5, 95% CI: 1.2 to 1.9). Viral infections were the most common STIs in recent years in a tertiary care center in Mumbai. HIV prevalence was high in this population. Thus, these clinical data suggest that STI patients were and continue to be an important group for HIV prevention in the country.

Credentialing for participation in clinical trials

International Nuclear Information System (INIS)

Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.

2012-01-01

The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

Credentialing for participation in clinical trials

Energy Technology Data Exchange (ETDEWEB)

Followill, David S. [Radiological Physics Center, Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Urie, Marcia [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Galvin, James M. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); Ulin, Kenneth [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); FitzGerald, Thomas J., E-mail: dfollowi@mdanderson.org [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States)

2012-12-26

The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

[Outlook for clinical hemorheology].

Science.gov (United States)

Stoltz, J F

1996-01-01

Harvey may be considered to be the precursor of modern hemorheology, but it was not until the pioneering work of Loewenhoeck, Poiseuille, Fahraeus and Copley that the essential role of the hemorheological properties of blood and its cellular components was recognized. Before the advent of modern hemorheology in the 70s, studies were mainly focussed on microcirculation and validation of global hemorheological equations applied to blood circulation. Parallel studies on the microrheological properties (erythrocyte deformability and aggregation) explained analytically the non-Newtonian behavior of blood, and the essential contribution of these parameters to the understanding hyperviscosity syndromes. The development of clinical hemorheology in fact started at the international conferences held in Reykjavik (1966) and Heidelberg (1969), and with the initiation of the periodical European Microcirculation (since Nancy in 1960) and Clinical Hemorheology (since Nancy in 1979) Conferences. The current main avenues of research involve flow modelling, studies of cell-cell interaction mechanisms (aggregation and adhesion), in relation to the associated pathophysiological phenomena, such as cellular activation (platelets and leukocytes in particular), gene expression linked to blood flow (e.g. endothelial cells)... Clinically and therapeutically, it is crucial that pathophysiological studies be undertaken on the relationship existing between rheological parameters and objective clinical data (local flow rates, ischemic markers, hemostatic parameters, tissue oxygen, clinical symptoms,...). The main clinical application fields are cardiovascular diseases, thrombosis, diabetes, hypercholesterolemia... Also, studies on new therapeutics or on biomaterials should also be given priority.

Assessing clinical reasoning abilities of medical students using clinical performance examination

Directory of Open Access Journals (Sweden)

Sunju Im

2016-03-01

Full Text Available Purpose: The purpose of this study is to investigate the reliability and validity of new clinical performance examination (CPX for assessing clinical reasoning skills and evaluating clinical reasoning ability of the students. Methods: Third-year medical school students (n=313 in Busan-Gyeongnam consortium in 2014 were included in the study. One of 12 stations was developed to assess clinical reasoning abilities. The scenario and checklists of the station were revised by six experts. Chief complaint of the case was rhinorrhea, accompanied by fever, headache, and vomiting. Checklists focused on identifying of the main problem and systematic approach to the problem. Students interviewed the patient and recorded subjective and objective findings, assessments, plans (SOAP note for 15 minutes. Two professors assessed students simultaneously. We performed statistical analysis on their scores and survey. Results: The Cronbach α of subject station was 0.878 and Cohen κ coefficient between graders was 0.785. Students agreed on CPX as an adequate tool to evaluate students’ performance, but some graders argued that the CPX failed to secure its validity due to their lack of understanding the case. One hundred eight students (34.5% identified essential problem early and only 58 (18.5% performed systematic history taking and physical examination. One hundred seventy-three of them (55.3% communicated correct diagnosis with the patient. Most of them had trouble in writing SOAP notes. Conclusion: To gain reliability and validity, interrater agreement should be secured. Students' clinical reasoning skills were not enough. Students need to be trained on problem identification, reasoning skills and accurate record-keeping.

Beninese vaccination clinic

Directory of Open Access Journals (Sweden)

Linda Sun

2017-04-01

Full Text Available This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

Nurses' Clinical Decision Making on Adopting a Wound Clinical Decision Support System.

Science.gov (United States)

Khong, Peck Chui Betty; Hoi, Shu Yin; Holroyd, Eleanor; Wang, Wenru

2015-07-01

Healthcare information technology systems are considered the ideal tool to inculcate evidence-based nursing practices. The wound clinical decision support system was built locally to support nurses to manage pressure ulcer wounds in their daily practice. However, its adoption rate is not optimal. The study's objective was to discover the concepts that informed the RNs' decisions to adopt the wound clinical decision support system as an evidence-based technology in their nursing practice. This was an exploratory, descriptive, and qualitative design using face-to-face interviews, individual interviews, and active participatory observation. A purposive, theoretical sample of 14 RNs was recruited from one of the largest public tertiary hospitals in Singapore after obtaining ethics approval. After consenting, the nurses were interviewed and observed separately. Recruitment stopped when data saturation was reached. All transcribed interview data underwent a concurrent thematic analysis, whereas observational data were content analyzed independently and subsequently triangulated with the interview data. Eight emerging themes were identified, namely, use of the wound clinical decision support system, beliefs in the wound clinical decision support system, influences of the workplace culture, extent of the benefits, professional control over nursing practices, use of knowledge, gut feelings, and emotions (fear, doubt, and frustration). These themes represented the nurses' mental outlook as they made decisions on adopting the wound clinical decision support system in light of the complexities of their roles and workloads. This research has provided insight on the nurses' thoughts regarding their decision to interact with the computer environment in a Singapore context. It captured the nurses' complex thoughts when deciding whether to adopt or reject information technology as they practice in a clinical setting.

21 CFR 862.3200 - Clinical toxicology calibrator.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

Mobile technology in clinical teaching.

Science.gov (United States)

Mackay, B J; Anderson, J; Harding, T

2017-01-01

Technology is having a profound effect on education in the 21st century and nurse educators are being challenged to integrate technological innovation to assist students in their learning. This paper reports a study on the introduction of smart mobile technology to support student learning in the clinical environment. In a climate of collaborative inquiry, clinical lecturers and two researchers from the same department carried out a project in three phases: formation, implementation and analysis. Following the formation phase, six clinical lecturers adopted iPads to support their clinical teaching (implementation phase). At this time they also kept reflective journals. In the analysis phase a thematic analysis of the data from the journals and from a focus group found both enabling and constraining factors influenced the use of iPads by clinical lecturers. The themes categorised as enablers were: resources and technology; and, management and technology support. Those identified as barriers or constraining factors were: clinical staff engagement; and lecturer experience with technology. Student engagement and learning, and connectivity were both enabling and constraining factors. This paper concludes that the use of a mobile device such as an iPad can enhance teaching in clinical settings but that in order for such devices to be successfully integrated into clinical teaching consideration needs to be given to professional development needs, adequate resourcing and technology support. Copyright © 2016 Elsevier Ltd. All rights reserved.

The pattern of clinical advice sought by general practitioners from a medical consultant in clinical biochemistry.

Science.gov (United States)

Bhatnagar, D

1997-01-01

Clinical biochemistry departments can be a valuable source of clinical advice for further investigations and the need for referral to specialist clinics. This paper outlines the pattern of clinical advice sought by general practitioners in a district hospital setting, and addresses some of the issues regarding seeking such advice and the implications for continuing medical education and training. PMID:9196966

LIMS and Clinical Data Management.

Science.gov (United States)

Chen, Yalan; Lin, Yuxin; Yuan, Xuye; Shen, Bairong

2016-01-01

In order to achieve more accurate disease prevention, diagnosis, and treatment, clinical and genetic data need extensive and systematically associated study. As one way to achieve precision medicine, a laboratory information management system (LIMS) can effectively associate clinical data in a macrocosmic aspect and genomic data in a microcosmic aspect. This chapter summarizes the application of the LIMS in a clinical data management and implementation mode. It also discusses the principles of a LIMS in clinical data management, as well as the opportunities and challenges in the context of medical informatics.

Clinical Physiology: A Successful Academic and Clinical Discipline is Threatened in Sweden

Science.gov (United States)

Arheden, Hakan

2009-01-01

Clinical physiologists in Sweden are physicians (the majority with a PhD degree) with thorough training in system physiology and pathophysiology. They investigate patients in a functional approach and are engaged in basic and applied physiology teaching and research. In 1954, clinical physiology was founded as an independent academic and clinical…

Decision analysis. Clinical art or Clinical Science

Science.gov (United States)

1977-05-01

having helped some clients. Over the past half century, psychotherapy has faced a series of crises concerned with its transformation from an art to a...clinical science . These include validation of the effectiveness of various forms of therapy, validating elements of treatment programs and

Clinical Practice in Portuguese Sexology.

Science.gov (United States)

Alarcão, Violeta; Ribeiro, Sofia; Almeida, Joana; Giami, Alain

2017-11-17

Few studies explore the clinicians' knowledge, attitudes, and practices regarding sexuality, despite their role in the sexual-health socialization process. This study focuses on Portuguese sexologists engaged in clinical practice. It aims to characterize sexologists' sex education and training and their clinical practices, including diagnostic and therapeutic approaches. This research followed the methodology of an European survey on sexology as a profession (Euro-Sexo). From the 91 respondents who completed questionnaires, 51 (56%) were active in clinical practice. Results indicate that the Portuguese clinical sexologist is significantly older, predominantly male, has had training in sexology, performs more scientific research, and is more engaged in teaching activities when compared to nonclinical working sexologists. This article describes the main sexual problems presented by patients to Portuguese clinical sexologists and highlights differences in the professional groups and approaches toward treating these problems by medical doctors and nonmedical professionals. Results reinforce the idea that there are intra-European differences in the educational background of sexologists and reveal important variations in Portuguese sexologists' education, training, and clinical practice. The representations and practices of the sexologists in Portugal, as in other European countries, are embedded in cultural scenarios and sexual cultures, with implications for the clinical practice.

Personalizing medicine with clinical pharmacogenetics

Science.gov (United States)

Scott, Stuart A.

2012-01-01

Clinical genetic testing has grown substantially over the past 30 years as the causative mutations for Mendelian diseases have been identified, particularly aided in part by the recent advances in molecular-based technologies. Importantly, the adoption of new tests and testing strategies (e.g., diagnostic confirmation, prenatal testing, and population-based carrier screening) has often been met with caution and careful consideration before clinical implementation, which facilitates the appropriate use of new genetic tests. Although the field of pharmacogenetics was established in the 1950s, clinical testing for constitutional pharmacogenetic variants implicated in interindividual drug response variability has only recently become available to help clinicians guide pharmacotherapy, in part due to US Food and Drug Administration-mediated product insert revisions that include pharmacogenetic information for selected drugs. However, despite pharmacogenetic associations with adverse outcomes, physician uptake of clinical pharmacogenetic testing has been slow. Compared with testing for Mendelian diseases, pharmacogenetic testing for certain indications can have a lower positive predictive value, which is one reason for underutilization. A number of other barriers remain with implementing clinical pharmacogenetics, including clinical utility, professional education, and regulatory and reimbursement issues, among others. This review presents some of the current opportunities and challenges with implementing clinical pharmacogenetic testing. PMID:22095251

[New intensifying screens in clinical radiology. II. Examinations in clinical practice].

Science.gov (United States)

Freyschmidt, J; Saure, D; Hagemann, G

1976-09-01

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.

Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

Directory of Open Access Journals (Sweden)

Xiao Xu

2017-01-01

Full Text Available Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

Learning to be a midwife in the clinical environment; tasks, clinical practicum hours or midwifery relationships.

Science.gov (United States)

Ebert, Lyn; Tierney, Olivia; Jones, Donovan

2016-01-01

Discussions continue within the midwifery profession around the number of and type of clinical experiences required to ensure competent midwifery graduates. Introduction of the three year Bachelor of Midwifery in Australia, almost two decades ago, was intended to reduce the pressure students were under to complete their academic requirements whilst ensuring students developed midwifery practice that encapsulates the philosophical values of midwifery. Currently, midwifery students are mandated to achieve a minimum number of clinical skills and Continuity of Care Experience (CCE) relationships in order to register upon completion of their degree. To achieve these experiences, universities require students to complete a number of clinical practicum hours. Furthermore students are required to demonstrate competent clinical performance of a number of clinical skills. However, there is no evidence to date that a set number of experiences or hours ensures professional competence in the clinical environment. The aim of this paper is to promote discussion regarding the mandated requirements for allocated clinical practicum hours, specified numbers of clinical-based skills and CCE relationships in the context of learning to be a midwife in Australia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence-based clinical practice

DEFF Research Database (Denmark)

Garattini, Silvio; Jakobsen, Janus C; Wetterslev, Jørn

2016-01-01

was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading...

CLINICAL FEATURES OF ACUTE FEBRILE THROMBOCYTOPAENIA AMONG PATIENTS ATTENDING PRIMARY CARE CLINICS

Directory of Open Access Journals (Sweden)

Khairani Omar

2006-01-01

Full Text Available Introduction: Identifying clinical features that differentiate acute febrile thrombocytopaenia from acute febrile illness without thrombocytopaenia can help primary care physician to decide whether to order a full blood count (FBC. This is important because thrombocytopaenia in viral fever may signify more serious underlying aetiology like dengue infection.Objective: The aim of this study was to compare the clinical features of acute febrile patients with thrombocytopaenia and acute febrile patients without thrombocytopaenia.Methodology: This was a clinic-based cross-sectional study from May to November 2003. Consecutive patients presenting with undifferentiated fever of less than two weeks were selected from the Primary Care Centre of Hospital Universiti Kebangsaan Malaysia and Batu 9 Cheras Health Clinic. Clinical features of these patients were recorded and FBC examination was done for all patients. Thrombocytopaenia was defined as platelet count <150X109/L. The odds ratio of thrombocytopaenia for each presenting symptoms was calculated.Result: Seventy-three patients participated in this study. Among them, 45.2% had thrombocytopaenia. Myalgia and headache were common among all patients. However, nausea and vomiting occurred significantly more often among patients with thrombocytopaenia than in patients with normal platelet count (OR 2.2, 95% CI 1.1-4.5.Conclusion: Acute non-specific febrile patients presenting with symptoms of nausea and vomiting may have higher risk of thrombocytopaenia and should be seriously considered for FBC.

A sense inventory for clinical abbreviations and acronyms created using clinical notes and medical dictionary resources.

Science.gov (United States)

Moon, Sungrim; Pakhomov, Serguei; Liu, Nathan; Ryan, James O; Melton, Genevieve B

2014-01-01

To create a sense inventory of abbreviations and acronyms from clinical texts. The most frequently occurring abbreviations and acronyms from 352,267 dictated clinical notes were used to create a clinical sense inventory. Senses of each abbreviation and acronym were manually annotated from 500 random instances and lexically matched with long forms within the Unified Medical Language System (UMLS V.2011AB), Another Database of Abbreviations in Medline (ADAM), and Stedman's Dictionary, Medical Abbreviations, Acronyms & Symbols, 4th edition (Stedman's). Redundant long forms were merged after they were lexically normalized using Lexical Variant Generation (LVG). The clinical sense inventory was found to have skewed sense distributions, practice-specific senses, and incorrect uses. Of 440 abbreviations and acronyms analyzed in this study, 949 long forms were identified in clinical notes. This set was mapped to 17,359, 5233, and 4879 long forms in UMLS, ADAM, and Stedman's, respectively. After merging long forms, only 2.3% matched across all medical resources. The UMLS, ADAM, and Stedman's covered 5.7%, 8.4%, and 11% of the merged clinical long forms, respectively. The sense inventory of clinical abbreviations and acronyms and anonymized datasets generated from this study are available for public use at http://www.bmhi.umn.edu/ihi/research/nlpie/resources/index.htm ('Sense Inventories', website). Clinical sense inventories of abbreviations and acronyms created using clinical notes and medical dictionary resources demonstrate challenges with term coverage and resource integration. Further work is needed to help with standardizing abbreviations and acronyms in clinical care and biomedicine to facilitate automated processes such as text-mining and information extraction.

Humor During Clinical Practice: Analysis of Recorded Clinical Encounters.

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Phillips, Kari A; Singh Ospina, Naykky; Rodriguez-Gutierrez, Rene; Castaneda-Guarderas, Ana; Gionfriddo, Michael R; Branda, Megan; Montori, Victor

2018-01-01

Little is known about humor's use in clinical encounters, despite its many potential benefits. We aimed to describe humor during clinical encounters. We analyzed 112 recorded clinical encounters. Two reviewers working independently identified instances of humor, as well as information surrounding the logistics of its use. Of the 112 encounters, 66 (59%) contained 131 instances of humor. Humor was similarly frequent in primary care (36/61, 59%) and in specialty care (30/51, 59%), was more common in gender-concordant interactions (43/63, 68%), and was most common during counseling (81/112, 62%). Patients and clinicians introduced humor similarly (63 vs 66 instances). Typically, humor was about the patient's medical condition (40/131, 31%). Humor is used commonly during counseling to discuss the patient's medical condition and to relate to general life events bringing warmth to the medical encounter. The timing and topic of humor and its use by all parties suggests humor plays a role in the social connection between patients and physicians and allows easier discussion of difficult topics. Further research is necessary to establish its impact on clinicians, patients, and outcomes. © Copyright 2018 by the American Board of Family Medicine.

Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic.

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Cai, Sophie; Elze, Tobias; Bex, Peter J; Wiggs, Janey L; Pasquale, Louis R; Shen, Lucy Q

2017-04-01

To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns. For each of 16 previously identified VF loss patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10-20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test. 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often ≥ 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often 6D (p = 0.069). Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.

A nurse- and pharmacist-led treatment advice clinic for patients attending an HIV outpatient clinic.

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Griffiths, C; Miles, K; Aldam, D; Cornforth, D; Minton, J; Edwards, S; Williams, I

2007-05-01

This paper is a report of a study to map care pathways, examine the approach of different treatment advisors and explore the acceptability of a nurse- and pharmacist-led treatment advice clinic in order to aid decision-making for the future development and evaluation of the clinic. High levels of adherence to antiretroviral drugs are a prerequisite for a successful and durable virological and immunological response to HIV. Treatment guidelines acknowledge that adherence is a process, not a single event, and that adherence support must be integrated into clinical follow-up for all patients receiving these drugs. Data were collected between September 2004 and January 2005 through 17 consultation observations and 10 patient interviews in a specialist treatment advice clinic located within a central London HIV outpatient clinic providing care for over 2200 patients, of whom more than 1300 are taking highly active antiretroviral therapy. The nurses and pharmacist had similar consultation approaches, although follow-up care varied in extent. Benefits of the clinic approach included permitting patients to observe real tablets, tailoring regimens to lifestyles and telephone follow-up. These factors, particularly telephone support, were perceived by patients to assist with adherence. The role of telephone support, perceived to assist with initial adherence, requires further investigation. Future work is also needed to explore the health economics of this approach and to determine the actual impact of the clinic on clinical and adherence outcomes.

Ubiquitous Multicriteria Clinic Recommendation System.

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Chen, Toly

2016-05-01

Advancements in information, communication, and sensor technologies have led to new opportunities in medical care and education. Patients in general prefer visiting the nearest clinic, attempt to avoid waiting for treatment, and have unequal preferences for different clinics and doctors. Therefore, to enable patients to compare multiple clinics, this study proposes a ubiquitous multicriteria clinic recommendation system. In this system, patients can send requests through their cell phones to the system server to obtain a clinic recommendation. Once the patient sends this information to the system, the system server first estimates the patient's speed according to the detection results of a global positioning system. It then applies a fuzzy integer nonlinear programming-ordered weighted average approach to assess four criteria and finally recommends a clinic with maximal utility to the patient. The proposed methodology was tested in a field experiment, and the experimental results showed that it is advantageous over two existing methods in elevating the utilities of recommendations. In addition, such an advantage was shown to be statistically significant.

Redesigning a clinical mentoring program for improved outcomes in the clinical training of clerks

OpenAIRE

Lin, Chia-Der; Lin, Blossom Yen-Ju; Lin, Cheng-Chieh; Lee, Cheng-Chun

2015-01-01

Introduction: Mentorship has been noted as critical to medical students adapting to clinical training in the medical workplace. A lack of infrastructure in a mentoring program might deter relationship building between mentors and mentees. This study assessed the effect of a redesigned clinical mentoring program from the perspective of clerks. The objective was to assess the benefits of the redesigned program and identify potential improvements.Methods: A redesigned clinical mentoring program ...

Clinical trial optimization: Monte Carlo simulation Markov model for planning clinical trials recruitment.

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Abbas, Ismail; Rovira, Joan; Casanovas, Josep

2007-05-01

The patient recruitment process of clinical trials is an essential element which needs to be designed properly. In this paper we describe different simulation models under continuous and discrete time assumptions for the design of recruitment in clinical trials. The results of hypothetical examples of clinical trial recruitments are presented. The recruitment time is calculated and the number of recruited patients is quantified for a given time and probability of recruitment. The expected delay and the effective recruitment durations are estimated using both continuous and discrete time modeling. The proposed type of Monte Carlo simulation Markov models will enable optimization of the recruitment process and the estimation and the calibration of its parameters to aid the proposed clinical trials. A continuous time simulation may minimize the duration of the recruitment and, consequently, the total duration of the trial.

Celiac disease: clinical observations

Directory of Open Access Journals (Sweden)

Yu. A. Emel’yanova

2016-01-01

Full Text Available Presented clinical cases of patients with a diagnosis of gluten enteropathy in treatment in the department of gastroenterology Regional Clinical Hospital. The case is of interest to doctors of different specialties for the differential diagnosis of anemia and malabsorption syndrome, demonstrate both the classic version, and atypical forms of the disease course. Diagnosis of celiac disease is based on three key positions: clinical findings, histology and serological markers. The clinical picture of celiac disease is characterized by pronounced polymorphism, by going beyond the a gastroenterological pathology. For screening of gluten sensitive celiac typically used an antibody to tissue transglutaminase. Morphological research of the mucous membrane of the small intestine is the determining criterion in the diagnosis of celiac disease. The use of specific gluten-free diet leads to the positive dynamics of the disease and improve the quality of life of patients.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

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Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

The effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick's model.

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Maddineshat, Maryam; Hashemi, Mitra; Besharati, Reza; Gholami, Sepideh; Ghavidel, Fatemeh

2018-01-01

Clinical experience associated with the fear and anxiety of nursing students in the psychiatric unit. Mental health nursing instructors find it challenging to teach nursing students to deal with patients with mental disorders in an environment where they need to provide patient teaching and clinical decision-making based on evidence and new technology. To measure the effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick's model evaluation in the psychiatry unit of Imam Reza Hospital, Bojnurd, Iran. This cross-sectional study was carried out from 2011 to 2016 on 76 nursing students from a university as part of a clinical mental health course in two semesters. The students were selected by a non-probable convenient sampling method. After completing their clinical education, each student responded to checklist questions based on the four-level Kirkpatrick's model evaluation and open questions relating to clinical supervision. Finally, all data was analyzed using the SPSS version 16. The students have evaluated clinical supervision as a useful approach, and appreciated the instructor's supportive behavior during teaching and imparting clinical skills. This has made them feel relaxed at the end of the clinical teaching course. In addition, in the evaluation through Kirkpatrick's model, more than 70% of the students have been satisfied with the method of conducting the teaching and average score of nursing students' attitude toward mental health students: Their mean self-confidence score was 18.33±1.69, and the mean score of their performance in the study was evaluated to be 93.74±5.3 from 100 points. The results of clinical mental health teaching through clinical supervision and Kirkpatrick's model evaluation show that the satisfaction, self-esteem, attitude, and skill of nursing students are excellent, thereby portraying the effectiveness of clinical teaching. But this program still needs to be reformed. To

Medical Paraclinical Standards, Political Economy of Clinic, and Patients’ Clinical Dependency; A Critical Conversation Analysis of Clinical Counseling in South of Iran

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Kalateh Sadati, Ahmad; Iman, Mohammad Taghi; Bagheri Lankarani, Kamran

2014-01-01

Background: Despite its benefits and importance, clinical counseling affects the patient both psychosocially and socially. Illness labeling not only leads to many problems for patient and his/her family but also it imposes high costs to health care system. Among various factors, doctor-patient relationship has an important role in the clinical counseling and its medical approach. The goal of this study is to evaluate the nature of clinical counseling based on critical approach. Methods: The context of research is the second major medical training center in Shiraz, Iran. In this study, Critical Conversation Analysis was used based on the methodologies of critical theories. Among about 50 consultation meetings digitally recorded, 33 were selected for this study. Results: Results show that the nature of doctor-patient relationship in these cases is based on paternalistic model. On the other hand, in all consultations, the important values that were legitimated with physicians were medical paraclinical standards. Paternalism in one hand and standardization on the other leads to dependency of patients to the clinic. Conclusion: Although we can’t condone the paraclinical standards, clinical counseling and doctor-patient relationship need to reduce its dominance over counseling based on interpretation of human relations, paying attention to social and economical differences of peoples and biosocial and biocultural differences, and focusing on clinical examinations. Also, we need to accept that medicine is an art of interaction that can’t reduce it to instrumental and linear methods of body treatment. PMID:25349858

Medical paraclinical standards, political economy of clinic, and patients' clinical dependency; a critical conversation analysis of clinical counseling in South of iran.

Science.gov (United States)

Kalateh Sadati, Ahmad; Iman, Mohammad Taghi; Bagheri Lankarani, Kamran

2014-07-01

Despite its benefits and importance, clinical counseling affects the patient both psychosocially and socially. Illness labeling not only leads to many problems for patient and his/her family but also it imposes high costs to health care system. Among various factors, doctor-patient relationship has an important role in the clinical counseling and its medical approach. The goal of this study is to evaluate the nature of clinical counseling based on critical approach. The context of research is the second major medical training center in Shiraz, Iran. In this study, Critical Conversation Analysis was used based on the methodologies of critical theories. Among about 50 consultation meetings digitally recorded, 33 were selected for this study. RESULTS show that the nature of doctor-patient relationship in these cases is based on paternalistic model. On the other hand, in all consultations, the important values that were legitimated with physicians were medical paraclinical standards. Paternalism in one hand and standardization on the other leads to dependency of patients to the clinic. Although we can't condone the paraclinical standards, clinical counseling and doctor-patient relationship need to reduce its dominance over counseling based on interpretation of human relations, paying attention to social and economical differences of peoples and biosocial and biocultural differences, and focusing on clinical examinations. Also, we need to accept that medicine is an art of interaction that can't reduce it to instrumental and linear methods of body treatment.

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

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Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter

Clinical reasoning and critical thinking.

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da Silva Bastos Cerullo, Josinete Aparecida; de Almeida Lopes Monteiro da Cruz, Diná

2010-01-01

This study identifies and analyzes nursing literature on clinical reasoning and critical thinking. A bibliographical search was performed in LILACS, SCIELO, PUBMED and CINAHL databases, followed by selection of abstracts and the reading of full texts. Through the review we verified that clinical reasoning develops from scientific and professional knowledge, is permeated by ethical decisions and nurses values and also that there are different personal and institutional strategies that might improve the critical thinking and clinical reasoning of nurses. Further research and evaluation of educational programs on clinical reasoning that integrate psychosocial responses to physiological responses of people cared by nurses is needed.

The Group Objective Structured Clinical Experience: building communication skills in the clinical reasoning context.

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Konopasek, Lyuba; Kelly, Kevin V; Bylund, Carma L; Wenderoth, Suzanne; Storey-Johnson, Carol

2014-07-01

Students are rarely taught communication skills in the context of clinical reasoning training. The purpose of this project was to combine the teaching of communication skills using SPs with clinical reasoning exercises in a Group Objective Structured Clinical Experience (GOSCE) to study feasibility of the approach, the effect on learners' self-efficacy and attitude toward learning communication skills, and the effect of providing multiple sources of immediate, collaborative feedback. GOSCE sessions were piloted in Pediatrics and Medicine clerkships with students assessing their own performance and receiving formative feedback on communication skills from peers, standardized patients (SPs), and faculty. The sessions were evaluated using a retrospective pre/post-training questionnaire rating changes in self-efficacy and attitudes, and the value of the feedback. Results indicate a positive impact on attitudes toward learning communication skills and self-efficacy regarding communication in the clinical setting. Also, learners considered feedback by peers, SPs, and faculty valuable in each GOSCE. The GOSCE is an efficient and learner-centered method to attend to multiple goals of teaching communication skills, clinical reasoning, self-assessment, and giving feedback in a formative setting. The GOSCE is a low-resource, feasible strategy for experiential learning in communication skills and clinical reasoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cost-effective clinical pharmacy services in a veterans administration drop-in clinic.

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Scrivens, J J; Magalian, P; Crozier, G A

1983-11-01

Services provided by a clinical pharmacist in a Veterans Administration outpatient clinic are described. Patients who come to the drop-in clinic for prescription refill authorization or medication-related problems are seen by a pharmacist rather than by a physician. The pharmacist interviews the patient, reviews the medical records and prescription and nonprescription drug profile, assesses appropriateness of current drug use, and records findings in the progress notes. The pharmacist may recommend presciption refill, change of medication or dosage, discontinuation, referral to a physician or nurse practitioner, follow-up appointments, or laboratory tests. The physician must countersign the pharmacist's prescriptions, referrals, and requests for laboratory tests. The clinical pharmacist's services reduced demand for physicians' time, allowed patients direct access to the health-care provider suited to deal with medication-related problems, and provided improved continuity of care. Potential benefits are cost savings from discontinuation of inappropriate drug therapy and from use of a pharmacist instead of a physician. The number of hospital admissions related to adverse drug reactions also may be reduced.

MYCOPLASMA INFECTION: CLINICAL TYPES, VARIATIONS OF CLINICAL COURSE AND DIAGNOSTIC MISTAKES

Directory of Open Access Journals (Sweden)

M.S. Savenkova

2013-01-01

Full Text Available Aim: to assess clinical course of various types of mycoplasma infection during the last epidemic (September 2012 – February 2013 according to the positive results of serological analyses. Patients and methods: 3553 laboratory tests were performed, 177 (20% positive results of mycoplasma were detected. During the study clinical types, gender and age of patients were analyzed; special characteristics of clinical course of mycoplasma pneumonia were identified. Results: among 78 patients with pneumonia severe form was detected only in one. Twenty five percent of patients had ENT-diseases. The authors performed comparative analysis of antibacterial treatment (first-line and macrolides. The duration of X-ray changes depended on treatment scheme; the best results were achieved in children who were administered combined treatment with first-line (cephalosporin and macrolide in suspension. Conclusions: during the period of 2012–2013 yy pneumonia has had a moderate clinical course, rarely — with complications. In 25% of children diseases of ENT organs were diagnosed. Mycoplasma was most often associated with chlamydia and types 1 and 2 of herpes simplex viruses, which is necessary to be considered in determination of therapy regimen. In treatment it is preferably to use combination of cephalosporin and macrolide in suspension.

[Development of an ophthalmological clinical information system for inpatient eye clinics].

Science.gov (United States)

Kortüm, K U; Müller, M; Babenko, A; Kampik, A; Kreutzer, T C

2015-12-01

In times of increased digitalization in healthcare, departments of ophthalmology are faced with the challenge of introducing electronic clinical health records (EHR); however, specialized software for ophthalmology is not available with most major EHR sytems. The aim of this project was to create specific ophthalmological user interfaces for large inpatient eye care providers within a hospitalwide EHR. Additionally the integration of ophthalmic imaging systems, scheduling and surgical documentation should be achieved. The existing EHR i.s.h.med (Siemens, Germany) was modified using advanced business application programming (ABAP) language to create specific ophthalmological user interfaces for reproduction and moreover optimization of the clinical workflow. A user interface for documentation of ambulatory patients with eight tabs was designed. From June 2013 to October 2014 a total of 61,551 patient contact details were documented. For surgical documentation a separate user interface was set up. Digital clinical orders for documentation of registration and scheduling of operations user interfaces were also set up. A direct integration of ophthalmic imaging modalities could be established. An ophthalmologist-orientated EHR for outpatient and surgical documentation for inpatient clinics was created and successfully implemented. By incorporation of imaging procedures the foundation of future smart/big data analyses was created.

Automation in Clinical Microbiology

Science.gov (United States)

Ledeboer, Nathan A.

2013-01-01

Historically, the trend toward automation in clinical pathology laboratories has largely bypassed the clinical microbiology laboratory. In this article, we review the historical impediments to automation in the microbiology laboratory and offer insight into the reasons why we believe that we are on the cusp of a dramatic change that will sweep a wave of automation into clinical microbiology laboratories. We review the currently available specimen-processing instruments as well as the total laboratory automation solutions. Lastly, we outline the types of studies that will need to be performed to fully assess the benefits of automation in microbiology laboratories. PMID:23515547

Radiography student perceptions of clinical stressors.

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Mason, Starla L

2006-01-01

Technological change and the increasingly rapid pace of life in the United States and globally have contributed to increased levels of stress and burnout experienced by workers and their families. Although studies are available on the levels of workplace stress and burnout affecting radiographers, little to no research has been conducted to assess the stressors encountered by radiography students in the clinical environment. This study was designed to pinpoint the primary sources of stress for radiography students and to determine the most effective measures to alleviate the stress that students experience in the clinical environment. It also sought to identify the clinical activities and practices that enhance learning. A convenience sample of radiography students attending an Association of Collegiate Educators in Radiologic Technology meeting was surveyed. Students were asked to rank their greatest stressors in the clinical environment, the most desired qualities in a clinical instructor and clinical environment, and the clinical practices and activities that best enhance their learning. Descriptive statistics were used to report the results. Data were collected for 82 first-year and second-year students. Students identified 7 primary clinical stressors: fear of making a mistake/repeat, feeling unprepared/inexperienced, intimidation by staff and by instructors, difficult/critical patients, hurtful criticism, too much supervision and negative responses to questions/requests for help. Students indicated that more frequent feedback, availability of the clinical instructor and other staff, assurance that mistakes happen and the opportunity to make mistakes were clinical practices that eased stress. The majority of students cited hands-on learning and repetition as the clinical activities that most reinforced their learning. Summary Radiography students in this survey experience some of the same clinical stressors as radiographers and other allied health workers

Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

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Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

2013-01-01

Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

A sense inventory for clinical abbreviations and acronyms created using clinical notes and medical dictionary resources

Science.gov (United States)

Moon, Sungrim; Pakhomov, Serguei; Liu, Nathan; Ryan, James O; Melton, Genevieve B

2014-01-01

Objective To create a sense inventory of abbreviations and acronyms from clinical texts. Methods The most frequently occurring abbreviations and acronyms from 352 267 dictated clinical notes were used to create a clinical sense inventory. Senses of each abbreviation and acronym were manually annotated from 500 random instances and lexically matched with long forms within the Unified Medical Language System (UMLS V.2011AB), Another Database of Abbreviations in Medline (ADAM), and Stedman's Dictionary, Medical Abbreviations, Acronyms & Symbols, 4th edition (Stedman's). Redundant long forms were merged after they were lexically normalized using Lexical Variant Generation (LVG). Results The clinical sense inventory was found to have skewed sense distributions, practice-specific senses, and incorrect uses. Of 440 abbreviations and acronyms analyzed in this study, 949 long forms were identified in clinical notes. This set was mapped to 17 359, 5233, and 4879 long forms in UMLS, ADAM, and Stedman's, respectively. After merging long forms, only 2.3% matched across all medical resources. The UMLS, ADAM, and Stedman's covered 5.7%, 8.4%, and 11% of the merged clinical long forms, respectively. The sense inventory of clinical abbreviations and acronyms and anonymized datasets generated from this study are available for public use at http://www.bmhi.umn.edu/ihi/research/nlpie/resources/index.htm (‘Sense Inventories’, website). Conclusions Clinical sense inventories of abbreviations and acronyms created using clinical notes and medical dictionary resources demonstrate challenges with term coverage and resource integration. Further work is needed to help with standardizing abbreviations and acronyms in clinical care and biomedicine to facilitate automated processes such as text-mining and information extraction. PMID:23813539

Implementation and evaluation of Parkinson disease management in an outpatient clinical pharmacist-run neurology telephone clinic.

Science.gov (United States)

Stefan, Teodora Cristina; Elharar, Nicole; Garcia, Guadalupe

2018-05-01

Parkinson disease (PD) is a progressive, debilitating neurodegenerative disease that often requires complex pharmacologic treatment regimens. Prior to this clinic, there was no involvement of a clinical pharmacy specialist (CPS) in the outpatient neurology clinic at the West Palm Beach Veterans Affairs Medical Center. This was a prospective, quality-improvement project to develop a clinical pharmacist-run neurology telephone clinic and evaluate pharmacologic and nonpharmacologic interventions in an effort to improve the quality of care for patients with PD. Additionally, the CPS conducted medication education groups to 24 patients with PD and their caregivers, if applicable, at this medical center with the purpose of promoting patient knowledge and medication awareness. Medication management was performed via telephone rather than face to face. Only patients with a concomitant mental health diagnosis for which they were receiving at least one psychotropic medication were included for individual visits due to the established scope of practice of the CPS being limited to mental health and primary care medications. Data collection included patient and clinic demographics as well as pharmacologic and nonpharmacologic interventions made for patients enrolled from January 6, 2017, through March 31, 2017. A total of 49 pharmacologic and nonpharmacologic interventions were made for 10 patients. We successfully implemented and evaluated a clinical pharmacist-run neurology telephone clinic for patients with PD. Expansion of this clinic to patients with various neurological disorders may improve access to care using an innovative method of medication management expertise by a CPS.

Avoidable Technical and Clinical Denial Write-Off Management in Hospitals, Physician Offices, and Clinics.

Science.gov (United States)

Terra, Sandra Marlene; Byrne, Amanda

2016-01-01

This article reviews the various types of technical and clinical denials that are usually "written off" and proposes strategies to prevent this loss. For purposes of this writing, avoidable technical and clinical denial write-offs are defined as revenue lost from "first-pass" denials rejections. For example, a procedure that requires an authorization is performed without having had an authorization obtained. After appeals and attempts to recoup the revenue, often unsuccessful, the organization ultimately "writes off" the revenue as not collectable. The question to ask is: Are these claims really not collectable or can actionable steps be taken to conserve these dollars and improve the bottom line? Acute care hospitals, physician offices, and clinics. In today's environment, the need to manage costs is ubiquitous. Cost management is on the priority list of all savvy health care executives, even if margins are healthy, revenue is under pressure, and the magnitude of cost reduction needed is greater than what past efforts have achieved. As hospitals and physician clinics prioritize areas for improvement, reduction in lost revenue-especially avoidable lost revenue-should be at the top of the list. Attentively managing claim denial write-offs will significantly reduce lost revenue. There is significant interface between case management and the revenue cycle. Developing core competencies for reducing clinical and technical denials should be a critical imperative in overall cost management strategy. Case managers are well placed to prevent these unnecessary losses through accurate status determination and clinical documentation review. These clinical professionals can also provide insight into work flow and other processes inherent in the preauthorization process.

Psychological functioning in adolescents referred to specialist gender identity clinics across Europe: a clinical comparison study between four clinics.

Science.gov (United States)

de Graaf, Nastasja M; Cohen-Kettenis, Peggy T; Carmichael, Polly; de Vries, Annelou L C; Dhondt, Karlien; Laridaen, Jolien; Pauli, Dagmar; Ball, Juliane; Steensma, Thomas D

2018-07-01

Adolescents seeking professional help with their gender identity development often present with psychological difficulties. Existing literature on psychological functioning of gender diverse young people is limited and mostly bound to national chart reviews. This study examined the prevalence of psychological functioning and peer relationship problems in adolescents across four European specialist gender services (The Netherlands, Belgium, the UK, and Switzerland), using the Child Behavioural Checklist (CBCL) and the Youth Self-Report (YSR). Differences in psychological functioning and peer relationships were found in gender diverse adolescents across Europe. Overall, emotional and behavioural problems and peer relationship problems were most prevalent in adolescents from the UK, followed by Switzerland and Belgium. The least behavioural and emotional problems and peer relationship problems were reported by adolescents from The Netherlands. Across the four clinics, a similar pattern of gender differences was found. Birth-assigned girls showed more behavioural problems and externalising problems in the clinical range, as reported by their parents. According to self-report, internalising problems in the clinical range were more prevalent in adolescent birth-assigned boys. More research is needed to gain a better understanding of the difference in clinical presentations in gender diverse adolescents and to investigate what contextual factors that may contribute to this.

[Clinical reasoning in nursing, concept analysis].

Science.gov (United States)

Côté, Sarah; St-Cyr Tribble, Denise

2012-12-01

Nurses work in situations of complex care requiring great clinical reasoning abilities. In literature, clinical reasoning is often confused with other concepts and it has no consensual definition. To conduct a concept analysis of a nurse's clinical reasoning in order to clarify, define and distinguish it from the other concepts as well as to better understand clinical reasoning. Rodgers's method of concept analysis was used, after literature was retrieved with the use of clinical reasoning, concept analysis, nurse, intensive care and decision making as key-words. The use of cognition, cognitive strategies, a systematic approach of analysis and data interpretation, generating hypothesis and alternatives are attributes of clinical reasoning. The antecedents are experience, knowledge, memory, cues, intuition and data collection. The consequences are decision making, action, clues and problem resolution. This concept analysis helped to define clinical reasoning, to distinguish it from other concepts used synonymously and to guide future research.

Teaching clinical reasoning to medical students.

Science.gov (United States)

Gay, Simon; Bartlett, Maggie; McKinley, Robert

2013-10-01

Keele Medical School's new curriculum includes a 5-week course to extend medical students' consultation skills beyond those historically required for competent inductive diagnosis. Clinical reasoning is a core skill for the practice of medicine, and is known to have implications for patient safety, yet historically it has not been explicitly taught. Rather, it has been assumed that these skills will be learned by accumulating a body of knowledge and by observing expert clinicians. This course aims to assist students to develop their own clinical reasoning skills and promote their greater understanding of, and potential to benefit from, the clinical reasoning skills of others. The course takes place in the fourth or penultimate year, and is integrated with students' clinical placements, giving them opportunities to practise and quickly embed their learning. This course emphasises that clinical reasoning extends beyond initial diagnosis into all other aspects of clinical practice, particularly clinical management. It offers students a variety of challenging and interesting opportunities to engage with clinical reasoning across a wide range of clinical practice. It addresses bias through metacognition and increased self-awareness, considers some of the complexities of prescribing and non-pharmacological interventions, and promotes pragmatic evidence-based practice, information management within the consultation and the maximising of patient adherence. This article describes clinical reasoning-based classroom and community teaching. Early evaluation suggests that students value the course and benefit from it. © 2013 John Wiley & Sons Ltd.

Clinical Trials

Medline Plus

Full Text Available ... part. Randomization Most clinical trials that have comparison groups use randomization. This involves assigning patients to different comparison groups by chance, rather than choice. This ...

Clinical Simulation and Workflow by use of two Clinical Information Systems, the Electronic Health Record and Digital Dictation

DEFF Research Database (Denmark)

Schou Jensen, Iben; Koldby, Sven

2013-01-01

digital dictation and the EHR (electronic health record) were simulated in realistic and controlled clinical environments. Useful information dealing with workflow and patient safety were obtained. The clinical simulation demonstrated that the EHR locks during use of the integration of digital dictation......Clinical information systems do not always support clinician workflows. An increasing number of unintended clinical inci-dents might be related to implementation of clinical infor-mation systems and to a new registration praxis of unin-tended clinical incidents. Evidence of performing clinical...... simulations before implementation of new clinical information systems provides the basis for use of this method. The intention has been to evaluate patient safety issues, functionality, workflow, and usefulness of a new solution before implementation in the hospitals. Use of a solution which integrates...

Clinical roles in clinical biochemistry: a national survey of practice in the UK.

Science.gov (United States)

Choudhury, Sirazum M; Williams, Emma L; Barnes, Sophie C; Alaghband-Zadeh, Jamshid; Tan, Tricia M; Cegla, Jaimini

2017-05-01

Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com , and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

Clinical trials in orthopaedics and the future direction of clinical investigations for femoroacetabular impingement

DEFF Research Database (Denmark)

Clohisy, John C; Kim, Young-Jo; Lurie, Jon

2013-01-01

to be further defined. To date, clinical research reports have included primarily surgical case series. Future clinical investigations are needed to establish improved clinical evidence to guide patient care. Most urgent is the need to better understand the potential role of standardized nonsurgical treatment......Femoroacetabular impingement (FAI) represents a heterogeneous group of disorders that affect a diverse patient population. The natural history of the disease, the role of nonsurgical management, the indications for surgery, optimal surgical techniques, and the predictors of treatment outcomes need...... options for FAI and to define the predictors of surgical and nonsurgical outcomes. Future randomized controlled trials and large observational cohort studies targeted at these clinical research deficiencies will strengthen the evidence and improve informed decision making regarding the management...

A marketing clinical doctorate programs.

Science.gov (United States)

Montoya, Isaac D; Kimball, Olive M

2007-01-01

Over the past decade, clinical doctorate programs in health disciplines have proliferated amid both support and controversy among educators, professional organizations, practitioners, administrators, and third-party payers. Supporters argue that the explosion of new knowledge and increasing sophistication of technology have created a need for advanced practice models to enhance patient care and safety and to reduce costs. Critics argue that necessary technological advances can be incorporated into existing programs and believe that clinical doctorates will increase health care costs, not reduce them. Despite the controversy, many health disciplines have advanced the clinical doctorate (the most recent is the doctor of nursing practice in 2004), with some professions mandating the doctorate as the entry-level degree (i.e., psychology, pharmacy, audiology, and so on). One aspect of the introduction of clinical doctoral degrees has been largely overlooked, and that is the marketing aspect. Because of marketing considerations, some clinical doctorates have been more successfully implemented and accepted than others. Marketing is composed of variables commonly known as "the four P's of marketing": product, price, promotion, and place. This report explores these four P's within the context of clinical doctorates in the health disciplines.

Clinical neuropsychology in South Korea.

Science.gov (United States)

Kim, Myung-Sun; Chey, Jeanyung

2016-11-01

Clinical neuropsychology in South Korea, albeit its relatively short history, has advanced dramatically. We review a brief history and current status of clinical neuropsychology in South Korea. The history, the educational pathway, the training pathway, the certification process, and careers in clinical neuropsychology in South Korea are reviewed. We have reviewed the neuropsychological services, including assessment and treatment, research on neurological and psychiatric populations, and neuropsychology education and the requirements related to education, training, and board examinations of those providing neuropsychological services in South Korea. We also describe how the Korean Society for Neuropsychology Research, the first and only meeting for neuropsychologists in the country established in 1999, has played a major role in how clinical neuropsychology is practiced and developed as a professional field in South Korea. Clinical neuropsychology in South Korea has achieved major progress over just a quarter of a century, and its future is promising in light of the increasing demand for neuropsychological services and advances in neuroscience in the country. Challenges that the community of clinical neuropsychologists are currently facing in South Korea, including formalizing neuropsychological curriculum and training programs and developing advanced credentialing procedures, are discussed.