Factitious diarrhea

PubMed Central

Saibil, F. G.

1974-01-01

The causes of diarrhea are legion. In any diagnostic problem a factitious etiology must be carefully considered. Three cases are presented, in two of which daily ingestion of prunes and prune juice was found to be the cause of chronic diarrhea. In the third case an edible oil product, Coffee Rich, was determined by dietary manipulation to be the cause, carrageenan possibly being the laxative principle. PMID:4429937

Deceiving others/deceiving oneself: four cases of factitious rape.

PubMed

Feldman, M D; Ford, C V; Stone, T

1994-07-01

Although patients with factitious disorders typically seek the "patient" role through illness portrayals, some instead portray themselves falsely as "victims." We discuss the cases of four women who claimed to have been victims of rape; the allegations ultimately were disproved. Factitious rape may be prompted by a search for nurturance; by dissociation, leading individuals to believe that trauma earlier in life is ongoing; by a need to be rescued from real, current abuse; and by projection of anger onto specific male targets. Although dramatic, factitious rape is rare, we advocate thorough investigation of rape claims even when patients have known histories of deceptive behavior.

Munchausen Syndrome and the Wide Spectrum of Factitious Disorders.

PubMed

Tatu, Laurent; Aybek, Selma; Bogousslavsky, Julien

2018-01-01

Since its initial description in 1851, Munchausen syndrome has been widely used interchangeably with factitious disorder. Nevertheless, this syndrome is only one form of factitious disorder that is both severe and chronic. The syndrome was named after Karl Friedrich Hieronymus, Baron von Münchhausen (1720-1797), a German nobleman who became famous as a narrator of false and exaggerated exploits. His name was progressively corrupted to Munchausen. Factitious disorders and Munchausen syndrome remain a great diagnosis challenge for physicians. All medical specialities are concerned by these disorders. The diagnosis process involves a first step to exclude an unusual presentation of a common medical condition. The second step consists of excluding somatoform disorders and malingering. Unfortunately, the boundaries between factitious disorder, somatization, and malingering are often unclear. In 1977, the term "Munchausen's syndrome by proxy" was coined to define a situation where a person produces false symptoms in another one, especially a child. This term was extended to similar interactions between human and pets. Because varied conditions have been included in the definition of this syndrome, there is ongoing debate about alternative names. © 2018 S. Karger AG, Basel.

Frequency of ICD-10 factitious disorder: survey of senior hospital consultants and physicians in private practice.

PubMed

Fliege, Herbert; Grimm, Anne; Eckhardt-Henn, Annegret; Gieler, Uwe; Martin, Katharina; Klapp, Burghard F

2007-01-01

The authors surveyed physicians for frequency estimates of factitious disorder among their patients. Twenty-six physicians in independent practice and 83 senior hospital consultants in internal medicine, surgery, neurology, and dermatology participated. They completed a questionnaire including the estimated 1-year prevalence of factitious disorder among their patients. Frequency estimates averaged 1.3% (0.0001%-15%). The number of patients treated correlated negatively with frequency estimates. Dermatologists and neurologists gave the highest estimations. One-third of the physicians rated themselves as insufficiently informed. Frequency estimations did not differ by information level. The estimated frequency is substantial and comparable to earlier findings. Authors discuss clinical implications.

Factitious diarrhea induced by stimulant laxatives: accuracy of diagnosis by a clinical reference laboratory using thin layer chromatography.

PubMed

Shelton, Joseph H; Santa Ana, Carol A; Thompson, Donald R; Emmett, Michael; Fordtran, John S

2007-01-01

Surreptitious ingestion of laxatives can lead to serious factitious diseases that are difficult to diagnose. Most cases involve ingestion of bisacodyl or senna. Thin layer chromatography (TLC) of urine or stool is the only commercially available test for these laxatives. Such testing is considered highly reliable, but its accuracy in clinical practice is unknown. Our aim was to evaluate the reliability of TLC laxative testing by a clinical reference laboratory in the United States. Diarrhea was induced in healthy volunteers by ingestion of bisacodyl, senna, or a control laxative (n = 11 for each laxative group). Samples of urine and diarrheal stool were sent in blinded fashion to the clinical reference laboratory for bisacodyl and senna analysis. TLC testing for bisacodyl-induced diarrhea revealed a sensitivity of 73% and specificity of 91% when urine was tested and sensitivity and specificity of 91% and 96%, respectively, when stool was analyzed. When diarrhea was induced by senna, the TLC assay for senna failed to identify even a single urine or stool specimen as positive (zero% sensitivity). Considering the expected prevalence of surreptitious laxative abuse in patients with chronic idiopathic diarrhea (2.4%-25%, depending on the clinical setting), TLC of urine or stool for bisacodyl by this reference laboratory would often produce misleading results, and testing for senna would have no clinical value. The major problems are false-positive tests for bisacodyl and false-negative tests for senna.

[Somatic disorders, factitious disorders and simulation: the subtle art of differential diagnosis].

PubMed

Lleshi, V; Le Goff-Cubilier, V; Budry, P; Bryois, C

2007-04-04

In every day practice, it is difficult, sometimes impossible, and always ethically delicate to determine the differential diagnosis between: disorders of a somatic nature, simulation and factitious disorders, as much for the psychiatrist as for the general practitioner in the front line. Our aim is to lead a reflection on this controversial theme on the basis of a clinical illustration.

Artefactual skin lesions in children and adolescents: review of the literature and two cases of factitious purpura.

PubMed

Ring, Hans Christian; Miller, Iben M; Benfeldt, Eva; Jemec, Gregor B E

2015-01-01

Self harm is a great diagnostic and treatment challenge. In addition, psychocutaneous conditions are rare in the pediatric population and may therefore be misdiagnosed. Dermatitis artefacta is a psychocutaneous syndrome, which is a subgroup of the general spectrum of self-inflicted skin lesions. Dermatitis artefacta encompasses an array of different clinical manifestations, including purpura. Factitious purpura has rarely been reported in children. Case report and review of the literature. We describe two Caucasian patients (9-year-old boy and 10-year-old girl) with striking purpuric lesions diagnosed as factitious purpura. The clinical lesions were similar, but the underlying psychological problems differed significantly (depression and stress). The current state of knowledge of dermatitis artefacta in children and adolescents was reviewed. The presence of purpura in children and adolescents typically causes extensive intervention programs due to the possible serious pathological consequences. The two cases demonstrate a need for a high degree of attention to psychological disturbances, lesional evolution, and distribution once the suspicion is established. © 2014 The International Society of Dermatology.

A Therapeutic Confrontation Approach to Treating Patients with Factitious Illness

ERIC Educational Resources Information Center

Wedel, Kenneth R.

1971-01-01

Patients suffering from factitious illness present complex problems for themselves and hospital personnel. This article describes a multidisciplinary intervention through confrontation approach that has proved to be successful with such patients. (Author)

Factitious buccal lesion secondary to bruxism in a child with cerebral palsy

PubMed Central

Harris, D

2006-01-01

Children with cerebral palsy are at greater risk of a whole range of oral conditions than their peers. These include bruxism (tooth grinding), oral skill dysfunction, gross malocclusion due to effects of the abnormal orofacial muscle tone on tooth eruption, drooling of saliva, and poor oral hygiene.1 A challenging case of a painful buccal lesion in a 2 year old girl with cerebral palsy (CP) that did not respond to antifungal, antiviral or antibiotic treatment is presented as a factitious lesion. The recognition and significance of self‐injurious behaviour and factitious lesions in children are discussed. PMID:16373789

Factitious buccal lesion secondary to bruxism in a child with cerebral palsy.

PubMed

Harris, D

2006-01-01

Children with cerebral palsy are at greater risk of a whole range of oral conditions than their peers. These include bruxism (tooth grinding), oral skill dysfunction, gross malocclusion due to effects of the abnormal orofacial muscle tone on tooth eruption, drooling of saliva, and poor oral hygiene. A challenging case of a painful buccal lesion in a 2 year old girl with cerebral palsy (CP) that did not respond to antifungal, antiviral or antibiotic treatment is presented as a factitious lesion. The recognition and significance of self-injurious behaviour and factitious lesions in children are discussed.

Factitious Disorders and Cardiothoracic Surgery: The Ongoing Multidisciplinary Challenges of a Complex Case

PubMed Central

Firstenberg, Michael S.; Sirak, John H.; Sun, Benjamin; Kasick, David P.

2009-01-01

Chronic factitious disorder, Munchausen's syndrome, can be challenging to manage—particularly when complaints and symptoms suggest medical or surgical emergencies. We present a patient whose problems have spanned many years and a great distance. Hopefully, with a greater awareness of this disease, as this patient continues to seek health care in many different hospitals, the implications of timely access to information, good histories and physical exams, and an index of suspicion can assist in potentially avoiding unnecessary, expensive, and invasive evaluations. PMID:20029640

Factitious foods to reduce production costs of beneficial insects

USDA-ARS?s Scientific Manuscript database

This article reports the use of factitious foods such as Tenebrio molitor pupa, E. kuehniella eggs, Ephestia eggs, and or Artemia franciscana eggs for the rearing of beneficial insect such as Podisus maculiventris, spined soldier bug and several ladybird predators belonging to the Coccinellidae fam...

Factitious Disorder by Proxy in Educational Settings: A Review

ERIC Educational Resources Information Center

Frye, Ellen M.; Feldman, Marc D.

2012-01-01

Factitious disorder by proxy (FDP), historically known as Munchausen syndrome by proxy, is a diagnosis applied to parents and other caregivers who intentionally feign, exaggerate, and/or induce illness or injury in a child to get attention from health professionals and others. A review of the recent literature and our experience as consultants…

[Differences in insulin secretion facilitate the differential diagnosis of insulinoma and factitious hypoglycaemia].

PubMed

Meier, J J; Hücking, K; Grüneklee, D; Schmiegel, W; Nauck, M A

2002-02-22

A 33-year-old female nurse (married; two children; BMI 30.9 kg/m2) had recurrent episodes of symptomatic hypoglycaemia over some months. Two fasting tests were terminated after 26 hours because the patient became unconscious. Improved insulin/glucose ratio was infinity and 6.1 [mU/l]/[mg/dl] (normal value < 0.5). An hyperinsulinaemic-hypoglycaemic angle "clamp test" produced a C-peptide suppression to minimally 0.26 - 0.38 nmol/l (normal value 0.06 +/- 0.01 nmol). There was no spontaneous or paradoxical burst in insulin or C-peptide concentration after either the fasting or the "clamp test". Serum analysis of sulphonylurea on several occasions documented an increase of glibenclamide above therapeutic range. The patient denied any intake of oral antidiabetic preparations, but there were no further hypoglycaemia attacks in subsequent months. The demonstration of sulphonylurea in serum confirmed the diagnosis of factitious hypoglycaemia. With regard to insulin or C-peptide suppression, the results of the fasting and clamp tests are the same in factitious hypoglycaemia and insulinoma. However, under the influence of sulphonylurea drugs there are no insulin or C-peptide bursts so typical of insulinoma. In case of doubt, detection of sulphonylurea preparations in serum or urine is the only reliable way of diagnosing factitious hypoglaema due to the ingestion of sulphonylurea.

Factitious Disorder Presenting with Stuttering in Two Adolescents: The Importance of Psychoeducation.

PubMed

Bolat, Nurullah; Yalçin, Özhan

2017-03-01

A factitious disorder (FD) is a diagnostic entity in which patients intentionally act physically or mentally ill without obvious benefits and without being consciously aware of a clear underlying motive. Most pediatric FD cases have been reported as Munchausen syndrome by Proxy; however, pediatric disease symptoms can also be intentionally falsified by child and adolescent patients. To our knowledge, in the medical literature, an FD patient presenting with stuttering has not been previously reported. In this case report, we aimed to discuss the diagnosis and treatment process of FDs in children and adolescents by reporting the cases of two FD patients presenting with stuttering according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition. Both patients improved with psychoeducation and early confrontation.

Recognition of factitial hand injuries.

PubMed

Carlson, M J; Linscheid, R L; Lucas, A R

1977-01-01

Facitial injuries with various presentations occur with some frequency to the hand because it is a body part that is easily accessible. Methods used to produce wounds included insertion of porcupine quills, application of constrictive rubber bands, mascara injections and excoriation of healing wounds. It is important to recognize the factitial origin in order to avoid needless repetitive surgery and permanent hand disability. No specific pattern of psychopathology was found in our cases. The patients' attitude toward their lesions was one of bland unconcern and stoicism. The patients were resistant to psychiatric referral and persisted in seeking medical responsibility for cure. Successful management requires early suspicion and prompt recognition as well as establishment of non-accusatory relationship with the primary physician. Confrontation should be avoided if possible. Even if reinforced with collaborative evidence, such confrontation will have limited effect on the patient's subsequent behavior.

Factitious disorder: a rare cause of haematemesis.

PubMed

McFarlane, Michael; Eaden, Jayne; Burch, Nicola; Disney, Ben

2017-10-01

Acute upper gastrointestinal (GI) bleeding is a common condition in the UK with 50-70,000 admissions per year. In 20% of cases no cause can be found on endoscopy. Here, we present the case of a young female patient who was admitted on three occasions with large volume haematemesis and bleeding from other sites. She was extensively investigated and underwent multiple endoscopic procedures. She was eventually diagnosed with factitious disorder after concerns were raised about the inconsistent nature of her presentations. She was found to be venesecting herself from her intravenous cannula, and ingesting the blood to simulate upper GI bleeding. This is a rare cause of 'haematemesis' but perhaps not as rare as is thought.

Factitious thyrotoxicosis induced by mesotherapy: a case report.

PubMed

Danilovic, Debora Lucia Seguro; Bloise, Walter; Knobel, Meyer; Marui, Suemi

2008-06-01

Mesotherapy consists of cutaneous injections of a mixture of compounds and has recently been used for cosmetic purposes to reduce local fat and cellulite. To date, several reports have described only local adverse events related to this therapy. We describe the first report of a female patient who developed thyrotoxicosis due to cosmetic mesotherapy with triiodothyroacetic acid in its formulation. Apart from mechanical rupture of the epidermal barrier, a disturbance of type III deiodinase activity or skin fibroblast paracrine function and vascular alterations related to simultaneously injected vasoactive compounds were observed. These findings could be related to thyroid hormone metabolite absorption and systemic consequences in the reported case. We describe factitious thyrotoxicosis induced by mesotherapy, to raise awareness of a systemic adverse effect resulting from this widespread cosmetic practice.

Factitious hypoglycemia in pregnancy in a patient with type 2 diabetes.

PubMed

Vega Guedes, Begoña; Santana Acosta, Concepción; Cabrera, Francisco; Wägner, Ana M

2014-08-01

Glycemic control in pregnancy complicated by diabetes is important. Spontaneous symptomatic hypoglycemia, in the absence of glucose-lowering treatment, is rare and requires evaluation to prevent harm. As a result of hypoglycemia, a pregnant woman with type 2 diabetes mellitus had progressive reduction of her insulin requirements until treatment was discontinued at 27 weeks. Despite this, she reported persistent episodes of hypoglycemia. Investigation of possible causes resulted in the discovery that she was covertly treating herself with insulin. Factitious hypoglycemia should be considered as part of the differential diagnosis of unexplained hypoglycemia. Blood sampling during an episode of hypoglycemia is pivotal in this assessment.

[Münchhausen syndrome by proxy].

PubMed

Le Heuzey, M-F; Mouren, M-C

2008-01-01

Münchhausen syndrome by proxy is a factitious disorder, a disease produced or simulated by a parent, the mother in most cases. Clinical presentation is miscellaneous (factitious bleeding, epilepsy, apnea are frequent) and unusual. Physicians participate in the abuse by their therapeutic and diagnostical measures. It is very important to think about this diagnostic in any ambiguous situation in order to evaluate and protect the child.

Importance of Insulin Immunoassays in the Diagnosis of Factitious Hypoglycemia

PubMed Central

Nalbantoğlu Elmas, Özlem; Demir, Korcan; Soylu, Nusret; Çelik, Nilüfer; Özkan, Behzat

2014-01-01

We report two cases emphasizing the importance of insulin assays for evaluation of hypoglycemia in diabetic patients. Case 1 was a 96/12-year-old female patient with type 1 diabetes mellitus and case 2 was a 1010/12-year-old male patient with DIDMOAD. Both patients were on a basal-bolus insulin regimen. Both were admitted because of persistent hypoglycemia. Analyses of serum samples obtained at the time of hypoglycemia initially showed low insulin and C-peptide levels. Recurrent episodes of unexplained hypoglycemia necessitated measurement of insulin levels by using different insulin assays, which revealed hyperinsulinemic hypoglycemia with low C-peptide levels, findings which confirmed a diagnosis of factitious hypoglycemia. Surreptitious administration of insulin should not be excluded in diabetic patients with hypoglycemia without taking into account the rate of cross-reactivity of insulin analogues with the insulin assay used. PMID:25541899

Epidemiology and evolution of the diagnostic classification of factitious disorders in DSM-5

PubMed Central

Caselli, Ivano; Poloni, Nicola; Ielmini, Marta; Diurni, Marcello; Callegari, Camilla

2017-01-01

A systematic search for all case reports and case series of adult patients with factitious disorders (FD) in the databases MEDLINE, Scopus, and PsycINFO was conducted. FD is a psychiatric disorder in which sufferers intentionally fabricate physical or psychological symptoms in order to assume the role of a patient, without any obvious gain. The clinical and demographic profile of patients with FD has not been sufficiently clear. Thus, the aims of this study were to outline a demographic and clinical profile of a large sample of patients with FD and to study the evolution of the position of FD in the Diagnostic and Statistical Manual of Mental Disorders. One thousand six hundred thirty-six records were obtained based on key search terms, after exclusion of duplicate records. Five hundred seventy-seven articles were identified as potentially eligible for the study, of which 314 studies were retrieved for full-text review. These studies included 514 cases. Variables extracted included age, gender, reported occupation, comorbid psychopathology, clinical presentation, and factors leading to the diagnosis of FD. In the sample, 65.4% of patients were females. Mean age at presentation was 33.5 years. A health care profession was reported most frequently (n=113). Patients were most likely to present in psychiatry, neurology, emergency, and internal medicine departments. The broad survey of sociodemographic profile of the sample has highlighted some important points for early diagnosis and early psychiatric treatment. The study showed that the patients did not meet Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria in 11.3% of cases. PMID:29270035

Factitious aortic dissection leading to thoracotomy in a 20-year-old man.

PubMed

Chambers, Elise; Yager, Joel; Apfeldorf, William; Camps-Romero, Eduardo

2007-01-01

A 20-year-old man presented to an emergency department with dramatic, sudden-onset, tearing chest pain. He also claimed to have been previously diagnosed with Ehler-Danlos syndrome and a previous Type I aortic dissection (intimal tear of ascending aorta), rapidly increasing his treating physician's suspicion of an emergent aortic dissection. The patient was quickly transferred to a large university hospital, where he underwent a median sternotomy and thoracotomy, with no aortic pathology found on operation and biopsy. After the patient's postoperative recovery, he was treated at a mental health facility, where he remained ambivalent about his psychiatric condition and did not respond well to treatment. This case report describes a unique case of factitious disorder that led to a serious operative intervention and subsequent psychiatric care and assesses factors that might have contributed to his hospital course.

Pediatric condition falsification (Munchausen syndrome by Proxy) as a continuum of maternal factitious disorder (Munchausen syndrome).

PubMed

Kucuker, Hudaverdi; Demir, Tevfik; Oral, Resmiye

2010-12-01

Pediatric condition falsification (PCF), also known as Munchausen syndrome by Proxy or Medical Child Abuse, is a somewhat rare form of child abuse and neglect. Its association with a history of adult factitious disorder (AFD) or Munchausen syndrome in the perpetrator is also well known. Exogenous insulin injection to cause hypoglycemia both in the context of PCF and AFD has been reported in the literature. However, the coexistence of both conditions via insulin injection in the same family has not been reported in the literature. This paper presents a family, in which the mother was diagnosed with AFD and her three children with PCF perpetrated by their mother via exogenous insulin injection. © 2010 John Wiley & Sons A/S.

Challenges of teacher-based clinical evaluation from nursing students' point of view: Qualitative content analysis.

PubMed

Sadeghi, Tabandeh; Seyed Bagheri, Seyed Hamid

2017-01-01

Clinical evaluation is very important in the educational system of nursing. One of the most common methods of clinical evaluation is evaluation by the teacher, but the challenges that students would face in this evaluation method, have not been mentioned. Thus, this study aimed to explore the experiences and views of nursing students about the challenges of teacher-based clinical evaluation. This study was a descriptive qualitative study with a qualitative content analysis approach. Data were gathered through semi-structured focused group sessions with undergraduate nursing students who were passing their 8 th semester at Rafsanjan University of Medical Sciences. Date were analyzed using Graneheim and Lundman's proposed method. Data collection and analysis were concurrent. According to the findings, "factitious evaluation" was the main theme of study that consisted of three categories: "Personal preferences," "unfairness" and "shirking responsibility." These categories are explained using quotes derived from the data. According to the results of this study, teacher-based clinical evaluation would lead to factitious evaluation. Thus, changing this approach of evaluation toward modern methods of evaluation is suggested. The finding can help nursing instructors to get a better understanding of the nursing students' point of view toward this evaluation approach and as a result could be planning for changing of this approach.

Don't Judge a Book by Its Cover: Factitious Disorder Imposed on Children-Report on 2 Cases

PubMed Central

Faedda, Noemi; Baglioni, Valentina; Natalucci, Giulia; Ardizzone, Ignazio; Camuffo, Mauro; Cerutti, Rita; Guidetti, Vincenzo

2018-01-01

Factitious Disorder Imposed on Another (FDIA), also known as Munchausen Syndrome by Proxy (MSbP) is a very serious form of child abuse. The perpetrator, usually the mother, invents symptoms or causes real ones in order to make her child appear sick. Usually this is due to a maladaptive disorder or to an excessive of attention-seeking on her part. We report here two new cases of FDIA. The first one is a 9-year-old boy with a history of convulsive episodes, reduced verbal production, mild psychomotor disorder and urological problems who underwent several invasive procedures and hospitalizations before a diagnosis of FDIA was made. The second is a 12 year-old girl with headache, abdominal pain, lipothymic episodes, seizures and a gait impairment, who was hospitalized in several hospitals before an FDIA was diagnosed. PMID:29721488

A case of Munchausen syndrome with claims of trauma and haemophilia.

PubMed Central

Park, G; Huang, A; Wright, S

1996-01-01

A case of Munchausen syndrome presented with both factitious trauma and factitious haemophilia. He was treated inappropriately with factor VIII concentrate before the history of the presenting complaint could be validated. Clinical suspicion remains the most important aid to diagnosis. Images Figure 1 PMID:8832359

Factitious Disorder

MedlinePlus

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Somatoform, factitious, and related diagnoses in the national hospital discharge survey: addressing the proposed DSM-5 revision.

PubMed

Hamilton, James C; Eger, Melike; Razzak, Saman; Feldman, Marc D; Hallmark, Natalie; Cheek, Stephen

2013-01-01

The DSM-5 working group on the somatoform (SFD) and factitious (FD) disorders has recommended substantial revisions of these categories. The recommendations are based, in part, on anecdotal evidence that the diagnoses are infrequently used. To assess the assignment rates for SFD, FD, and related diagnoses among general medical inpatients. The National Hospital Discharge Survey was queried for instances of SFD and FD, along with related diagnoses identifying medical cases in which psychological factors play a role. Diagnoses of major depression and generalized anxiety disorder were queried for comparison purposes. The target diagnoses were assigned far less frequently than published prevalence and recognition rates suggest. Nearly half of the assigned target diagnoses were generic diagnoses (esp. physiological malfunction due to psychological factors) other than SFD or FD. However, the apparent degree of underassignment of the target diagnoses was not dramatically greater than the underassignment observed for major depression and generalized anxiety disorder. The results provide empirical support for the impression that physicians do not assign SFD and FD diagnoses in recognized cases, but do not strongly support the assertion that these diagnoses are uniquely problematic. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Legionnaire's Disease: A Clinical Diagnostic Approach.

PubMed

Cunha, Burke A; Cunha, Cheston B

2017-03-01

Legionnaire's disease is a nonzoonotic atypical pneumonia caused by Legionella sp that occurs sporadically or in outbreaks. Legionnaire's disease pneumonia is accompanied by several extrapulmonary clinical and laboratory findings. Rather than testing all pneumonias for Legionnaire's disease, the clinical challenge is to recognize the diagnostic significance of Legionnaire's disease's. The pretest probability of Legionnaire's disease is increased if several characteristic extrapulmonary findings are present. Similarly, if certain key findings are absent, Legionnaire's disease may be eliminated from further diagnostic consideration. If characteristic clinical findings are present, then specific tests should be ordered to confirm or rule out Legionnaire's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Disease-mongering through clinical trials.

PubMed

González-Moreno, María; Saborido, Cristian; Teira, David

2015-06-01

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease Location.

PubMed

Aziz, Danish Abdul; Moin, Maryum; Majeed, Atif; Sadiq, Kamran; Biloo, Abdul Gaffar

2017-01-01

To determine different clinical presentationsand disease location demarcatedby upper and lower gastrointestinal endoscopyand relevant histopathologyin children diagnosed with inflammatory bowel disease (IBD). This is 5 years (2010 to 2015) retrospective studyconducted at the Aga Khan University Hospitalenrolling65admitted children between 6 months to 15years from either gender, diagnosed with IBD on clinical presentation, endoscopy and biopsy. Different clinical presentations at the time of diagnosis were noted in different categories of the disease. All patients underwent upper and lower (up to the terminal ileum) endoscopy with multiple punch biopsies and histologic assessment of mucosal specimens. All endoscopies were done by paediatric gastroenterologists at endoscopy suite of the hospital and all specimens were reported by the pathology department. ESPGHAN revised criteria for the diagnosis of inflammatory bowel disease in children and an adolescent was used to standardize our diagnosis. Extent of disease on endoscopy and relevant histopathology of the biopsy samples were noted at the time of diagnosis. Data was summarized using mean, standard deviation, numbers and percentages for different variables. Total 56 children were enrolled according to inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%) patients were labeled as Indeterminate colitis (IC). Mean age at onset of symptoms was10.03±2.44 and mean age at diagnosis was11.10±2.36. Abdominal pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC. Patients diagnosed with indeterminate colitis(IC) had similar clinical features as in UC patients. Only 7% patients had some extra-intestinal features in the form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 ±12.89) was relatively high in

Clinically Unsuspected Prion Disease Among Patients With Dementia Diagnoses in an Alzheimer's Disease Database.

PubMed

Maddox, Ryan A; Blase, J L; Mercaldo, N D; Harvey, A R; Schonberger, L B; Kukull, W A; Belay, E D

2015-12-01

Brain tissue analysis is necessary to confirm prion diseases. Clinically unsuspected cases may be identified through neuropathologic testing. National Alzheimer's Coordinating Center (NACC) Minimum and Neuropathologic Data Set for 1984 to 2005 were reviewed. Eligible patients had dementia, underwent autopsy, had available neuropathologic data, belonged to a currently funded Alzheimer's Disease Center (ADC), and were coded as having an Alzheimer's disease clinical diagnosis or a nonprion disease etiology. For the eligible patients with neuropathology indicating prion disease, further clinical information, collected from the reporting ADC, determined whether prion disease was considered before autopsy. Of 6000 eligible patients in the NACC database, 7 (0.12%) were clinically unsuspected but autopsy-confirmed prion disease cases. The proportion of patients with dementia with clinically unrecognized but autopsy-confirmed prion disease was small. Besides confirming clinically suspected cases, neuropathology is useful to identify unsuspected clinically atypical cases of prion disease. © The Author(s) 2015.

Life cycle of Cosmolaelaps jaboticabalensis (Acari: Mesostigmata: Laelapidae) on Frankliniella occidentalis (Thysanoptera: Thripidae) and two factitious food sources.

PubMed

Moreira, Grazielle Furtado; de Morais, Matheus Rovere; Busoli, Antônio Carlos; de Moraes, Gilberto José

2015-02-01

The aim of this work was to study the life cycle of Cosmolaelaps jaboticabalensis Moreira, Klompen and Moraes preying on Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), a serious cosmopolitan pest of different crops, as well as on Protorhabditis sp. (Nematoda: Rhabditidae) and Tyrophagus putrescentiae (Astigmatina: Acaridae), prospective factitious foods for the mass rearing of the predator. Experiments were conducted in a chamber at 25 ± 1 °C, 70 ± 10 % RH and in the dark. Total immature development (egg-adult) was completed in 12.3 ± 5, 6.6 ± 0.6 and 7.1 ± 0.6 on F. occidentalis, Protorhabditis sp. and T. putrescentiae, respectively. Fecundity and intrinsic rate of increase were higher on Protorhabditis sp. (71.6 ± 9.1 eggs/female; 0.28 female/female/day) than on F. occidentalis (63.8 ± 14.8; 0.23) and T. putrescentiae (43.1 ± 8.9; 0.23). Cosmolaelaps jaboticabalensis reproduces by thelytokous parthenogenesis and its larval stages can be completed without feeding. Protonymphs and deutonymphs can survive in the absence of food for about a month, and adults for almost 2 months. It was concluded that C. jaboticabalensis is a promising biological control agent of F. occidentalis and that it may be mass reared with the use of Protorhabditis sp. or T. putrescentiae.

Recruitment of subjects into clinical trials for Alzheimer disease.

PubMed

Knebl, Janice A; Patki, Deepti

2010-09-01

Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

Clinical aspects of autoimmune rheumatic diseases.

PubMed

Goldblatt, Fiona; O'Neill, Sean G

2013-08-31

Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.

PubMed

Hamrahian, Amir H; Yuen, Kevin C J; Hoffman, Andrew R

2014-07-01

To review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice. PubMed searches were performed to identify all of the available published data on medical management of Cushing disease. Medical therapy is usually not the first-line treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase. Medical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies.

Clinical and Histologic Mimickers of Celiac Disease.

PubMed

Kamboj, Amrit K; Oxentenko, Amy S

2017-08-17

Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

Learning disease relationships from clinical drug trials.

PubMed

Haslam, Bryan; Perez-Breva, Luis

2017-01-01

Our objective is to test the limits of the assumption that better learning from data in medicine requires more granular data. We hypothesize that clinical trial metadata contains latent scientific, clinical, and regulatory expert knowledge that can be accessed to draw conclusions about the underlying biology of diseases. We seek to demonstrate that this latent information can be uncovered from the whole body of clinical trials. We extract free-text metadata from 93 654 clinical drug trials and introduce a representation that allows us to compare different trials. We then construct a network of diseases using only the trial metadata. We view each trial as the summation of expert knowledge of biological mechanisms and medical evidence linking a disease to a drug believed to modulate the pathways of that disease. Our network representation allows us to visualize disease relationships based on this underlying information. Our disease network shows surprising agreement with another disease network based on genetic data and on the Medical Subject Headings (MeSH) taxonomy, yet also contains unique disease similarities. The agreement of our results with other sources indicates that our premise regarding latent expert knowledge holds. The disease relationships unique to our network may be used to generate hypotheses for future biological and clinical research as well as drug repurposing and design. Our results provide an example of using experimental data on humans to generate biologically useful information and point to a set of new and promising strategies to link clinical outcomes data back to biological research. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization.

PubMed

Rossitto, Giacomo; Battistel, Michele; Barbiero, Giulio; Bisogni, Valeria; Maiolino, Giuseppe; Diego, Miotto; Seccia, Teresa M; Rossi, Gian Paolo

2018-02-01

The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS. In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively). Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

[Clinical Tests Testing New Therapies for Stargardt Disease].

PubMed

Kousal, B; Ďuďáková, Ľ; Hlavatá, L; Lišková, P

2016-02-01

To provide information on currently ongoing clinical trials for Stargardt disease. We have searched the clinical trial register (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing studies. There are currently eight registered clinical trials enrolling patients with Stargardt disease; all in phase I or II aiming at four mechanisms of action: inhibition of the production of vitamin A toxic dimers, gene therapy restoring wild type transcription of the ABCA4 gene, neuroprotection preventing retinal cells from oxidative damage, and replacement of the damaged retinal pigment epithelium using stem cell therapy. The basic prerequisite for enrolment in the vast majority of clinical trials is confirmation of the clinical diagnosis by mutational analysis. The wide variety of therapies that are registered as clinical trials for Stargardt disease significantly raises the possibility that effective treatments will be available in the near future for this currently incurable condition and that molecular genetic testing should be increasingly considered. Stargardt disease, clinical trial, ABCA4, mutation.

A clinical approach to Lyme disease.

PubMed

Nadelman, R B; Wormser, G P

1990-05-01

Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development.

Lewy Body Disease: Clinical and Pathological "Overlap Syndrome" Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease).

PubMed

Foguem, Clovis; Manckoundia, Patrick

2018-04-08

Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics. This manuscript discusses current understanding of overlapping symptoms and the particular features of LBD, PD, and AD. It also describes features that could facilitate the diagnosis of each of these diseases. We concluded that the concept of neurodegenerative "overlap" syndrome, which includes the accepted diagnosis of LBD, may be taken in account and should contribute to clarifying LBD and definitions of close differential diagnoses. This should allow clinicians to suspect LBD at an earlier stage and provide better patient care.

A Case of Munchausen Syndrome Presenting with Hematemesis: A Case Report

PubMed Central

Aadil, Muhammad; Faraz, Aniqa; Anwar, Muhammad Jahanzaib; Nasir, Usama; Akhlaq, Anum

2017-01-01

Munchausen syndrome (MS) was first reported in 1951 by Richard Alan John Asher as a factitious disorder. It is a condition in which the patient intentionally produces symptoms to assume a sick role and gain medical attention. Underdiagnosis of this disorder results in the unnecessary use of medical resources, i.e. unnecessary medical tests and evaluations. This makes it one of the most challenging diagnosis in any medical set up. We present this rare case of a patient with chronic factitious disorder who presented to the emergency with hematemesis. The patient was successfully treated with psychotherapy with no recurrence. It is the need of the hour to create awareness amongst the medical and nonmedical population about factitious disorders so that they can easily be diagnosed and treated with efficiency. Further research is needed to find the risks leading to this syndrome and discover the cultural and social aspects of this disease, which may help us explore treatment strategies and avoid unnecessary tests and treatment.​ PMID:28979830

Lyme disease: clinical diagnosis and treatment

PubMed Central

Hatchette, TF; Davis, I; Johnston, BL

2014-01-01

Background Lyme disease is an emerging zoonotic infection in Canada. As the Ixodes tick expands its range, more Canadians will be exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease. Objective To review the clinical diagnosis and treatment of Lyme disease for front-line clinicians. Methods A literature search using PubMed and restricted to articles published in English between 1977 and 2014. Results Individuals in Lyme-endemic areas are at greatest risk, but not all tick bites transmit Lyme disease. The diagnosis is predominantly clinical. Patients with Lyme disease may present with early disease that is characterized by a “bull’s eye rash”, fever and myalgias or with early disseminated disease that can manifest with arthralgias, cardiac conduction abnormalities or neurologic symptoms. Late Lyme disease in North America typically manifests with oligoarticular arthritis but can present with a subacute encephalopathy. Antibiotic treatment is effective against Lyme disease and works best when given early in the infection. Prophylaxis with doxycyline may be indicated in certain circumstances. While a minority of patients may have persistent symptoms, evidence does not demonstrate that prolonged courses of antibiotics improve outcome. Conclusion Clinicians need to be aware of the signs and symptoms of Lyme disease. Knowing the regions where Borrelia infection is endemic in North America is important for recognizing patients at risk and informing the need for treatment. PMID:29769842

Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists.

PubMed

Lee, Hwajeong; Westerhoff, Maria; Shen, Bo; Liu, Xiuli

2016-05-01

-Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. -To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. -The literature was reviewed. -Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.

A case of bullous dermatitis artefacta possibly induced by a deodorant spray.

PubMed

Ikenaga, Satsuki; Nakano, Hajime; Umegaki, Noriko; Moritsugu, Ryuta; Aizu, Takayuki; Kuribayashi, Michihito; Hanada, Katsumi

2006-01-01

Dermatitis artefacta is one of a spectrum of factitious diseases etiologically responsible for skin lesions denied by patients. These factors often make it difficult to identify the causative agents of the condition. Herein, we report a case of bullous dermatitis artefacta in a 12-year-old girl, for which a deodorant spray was suspected as the probable cause. Pathological examination revealed subepidermal blistering with full-thickness necrosis of the epidermis, suggesting a thermo- or cryo-induced injury. Psychological testing demonstrated her immaturity and dependence. In searching for the causative agent, we suspected a deodorant spray as a blister-inducing agent. We succeeded in reproducing a similar blister lesion on the volunteer's healthy skin using the same spray. Psychiatric involvement significantly complicates the treatment of factitious diseases, including dermatitis artefacta. Cooperation among dermatologists, psychiatrists and the patient's family members is required for ensuring a favorable prognosis.

[Clinical and genetic special features of Niemann-Pick disease, type C].

PubMed

Zakharova, E Iu; Mikhaĭlova, S V; Proshliakova, T Iu; Rudenskaia, G E

2012-01-01

Niemann-Pick disease, type C is a rare hereditary disorder of the group of lisosomal storage diseases, caused by mutations in the genes NPC1 or NPC2. Depending on the onset age, several clinical forms of this disease, which differs by manifestation age, main clinical signs and clinical course, are distinguished. Niemann-Pick disease type C can imitate other hereditary and acquired diseases, which complicates its early diagnostics. Clinical and genetic diversity of this disorder, considered on the clinical cases diagnosed at the FSI "RCMG" of RAMS, are discussed in this review.

Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes

PubMed Central

Scharfe, Curt; Lu, Henry Horng-Shing; Neuenburg, Jutta K.; Allen, Edward A.; Li, Guan-Cheng; Klopstock, Thomas; Cowan, Tina M.; Enns, Gregory M.; Davis, Ronald W.

2009-01-01

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the

[Dopamine agonists--clinical applications beyond Parkinson's disease].

PubMed

Kuran, Włodzimierz

2007-01-01

Contemporary experience and results of clinical trials concerning dopamine agonist application in the treatment of many different diseases (apart from Parkinson's disease) are presented in the paper. A basic clinical recommendation for agonists is restless legs syndrome. In this syndrome almost all agonists give a considerable subjective and objective improvement. Treatment of atypical parkinsonism (MSA, PSP, CBD) in the majority of patients is ineffective. The author also presents promising results of treatment with agonists in such diverse diseases as hyperkinetic syndromes, cocaine dependence, drug-resistant depression and erectile dysfunction (apomorphine). Dopamine partial agonists (e.g. aripiprazol) are recommended in the modern treatment of schizophrenia.

[Münchausen syndrome by proxy. A case report].

PubMed

Moussaoui, A; Fejjal, N; Ababou, K; Tourabi, K; Ennouhi, A; Ribag, Y; Slaoui, A; Sqalli, J; Ihrai, H

2009-02-01

The plastic surgeon rarely encounters patients with factitious disorders. The syndrome of Münchausen by proxy is a part of it. We put the point on this syndrome through a clinical observation of an eight-year-old girl victim of parental abuse.

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

PubMed

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

Clinical pharmacology of novel anti-Alzheimer disease modifying medications.

PubMed

Caraci, Filippo; Bosco, Paolo; Leggio, Gian Marco; Malaguarnera, Michele; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

2013-01-01

In recent years, efforts have been directed to develop "disease-modifying" medications to treat Alzheimer's disease (AD), able to halt or slow the pathological process. Because the earlier the treatment starts, the greater is the possibility of efficacy, it is important to set up biomarkers for early diagnosis of functional brain abnormalities, before the clinical manifestation of the overt disease. Up to now, strategies to develop disease-modifying drugs have mainly targeted β amyloid (Aβ, accumulation, aggregation, clearance) and/or tau protein (phosphorylation and aggregation). Active and passive immunotherapy is the main strategy aimed at increasing Aβ clearance. Unfortunately several candidate diseasemodifying drugs have failed in phase III clinical trials conducted in mild to moderate AD. More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. Several methological problems have been recently pointed out to explain the lack of clinical efficacy of novel disease-modifying drug-treatments; moreover, new insights in pathophysiology of AD give the premise to develop novel drug targeting. Clinical trials recently completed and/or still ongoing are discussed in the present review.

Epileptic activity in Alzheimer’s disease: causes and clinical relevance

PubMed Central

Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

2018-01-01

Epileptic activity is frequently associated with Alzheimer’s disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer’s disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer’s disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer’s disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer’s disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer’s disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer’s disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline. PMID:28327340

Clinical trials in predementia stages of Alzheimer disease.

PubMed

Pillai, Jagan A; Cummings, Jeffrey L

2013-05-01

Effective treatments of Alzheimer disease (AD) dementia are an urgent necessity. There is a growing consensus that effective disease-modifying treatment before the onset of clinical dementia and slowing the progression of mild symptoms are needed after recent setbacks in AD therapeutics. The identification of at-risk and preclinical AD populations is becoming important for targeting primary and secondary prevention clinical trials in AD. This article reviews the strategies and challenges in targeting at-risk and preclinical AD populations for a new generation of AD clinical trials. Design, outcome measures, and complexities in successfully completing a clinical trial targeting this population are reviewed. Copyright © 2013 Elsevier Inc. All rights reserved.

[Psychoanalysis of self injury].

PubMed

Plassmann, R

1995-08-02

Psychoanalytic aspects of diseases with self-inflicted mutilation (factitious diseases and Munchhausen syndrome) have been investigated increasingly within the last years in the setting of long term ambulatory and hospital treatments. The author describes in this report how these disease states may also be interpreted as equivalents of remembrance and can be understood as inadequate attempts for self assistance. He outlines possibilities for psychotherapy arising in view of this background.

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

Ethical clinical translation of stem cell interventions for neurologic disease.

PubMed

Cote, David J; Bredenoord, Annelien L; Smith, Timothy R; Ammirati, Mario; Brennum, Jannick; Mendez, Ivar; Ammar, Ahmed S; Balak, Naci; Bolles, Gene; Esene, Ignatius Ngene; Mathiesen, Tiit; Broekman, Marike L

2017-01-17

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease. © 2016 American Academy of Neurology.

NASPGHAN Clinical Report on Postoperative Recurrence in Pediatric Crohn Disease.

PubMed

Splawski, Judy B; Pffefferkorn, Marian D; Schaefer, Marc E; Day, Andrew S; Soldes, Oliver S; Ponsky, Todd A; Stein, Philip; Kaplan, Jess L; Saeed, Shehzad A

2017-10-01

Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.

Monogenic Autoinflammatory Diseases: Concept And Clinical Manifestations

PubMed Central

De Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela

2013-01-01

The objectives of this review are to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary “periodic fever syndromes”, familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) 6. very rare conditions presenting with autoinflammation and immunodeficiency. PMID:23711932

Celiac disease in non-clinical populations of Japan.

PubMed

Fukunaga, Mai; Ishimura, Norihisa; Fukuyama, Chika; Izumi, Daisuke; Ishikawa, Nahoko; Araki, Asuka; Oka, Akihiko; Mishiro, Tomoko; Ishihara, Shunji; Maruyama, Riruke; Adachi, Kyoichi; Kinoshita, Yoshikazu

2018-02-01

Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease. Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests. Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings. The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms.

Clinical applications of fundus autofluorescence in retinal disease.

PubMed

Yung, Madeline; Klufas, Michael A; Sarraf, David

2016-01-01

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

Phenotype and Clinical Course of Inflammatory Bowel Disease with Co-Existent Celiac Disease.

PubMed

Tse, Chung Sang; Deepak, Parakkal; De La Fuente, Jaime; Bledsoe, Adam C; Larson, Joseph J; Murray, Joseph A; Papadakis, Konstantinos A

2018-05-07

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, and celiac disease are among the most common immune-mediated gastrointestinal diseases. We aim to elucidate the clinical course and outcomes of patients with concomitant inflammatory bowel disease and celiac disease, a unique population that remains scarcely studied to date. A retrospective matched case-control study of adults with coexistent inflammatory bowel disease and celiac disease was performed at a tertiary referral institution in North America. Logistic regression and Kaplan-Meier curves compared disease characteristics and clinical outcomes of the two groups. A total of 342 inflammatory bowel disease patients were included in this study, of which 114 had coexistent celiac disease and 228 did not. Patients with coexistent inflammatory bowel disease and celiac disease had higher rates of primary sclerosing cholangitis (19.3% vs 5.7%; odds ratio, 4.4; 95% confidence interval, 2.1-9.4; p<0.001), extensive ulcerative colitis (78.1% vs 59.0%; odds ratio, 2.8; 95% confidence interval 1.5-5.5, p=0.002), and family history of celiac disease (10.5% vs 3.5%; odds ratio 3.2; 95% confidence interval 1.3-8.2; p=0.01), compared to patients without concomitant celiac disease. Patients with inflammatory bowel disease with concomitant celiac disease have unique phenotypic features compared to non-celiac inflammatory bowel disease, with higher risks for colitis-related hospitalizations, extensive colitis, and primary sclerosing cholangitis. Increased recognition of coexistent IBD and celiac disease can prompt clinicians to investigate for concomitant disease sooner, particularly in patients with seemingly refractory disease.

Mitochondrial Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Clinical Frontiers

PubMed Central

Thornton, Ben; Cohen, Bruce; Copeland, William; Maria, Bernard L.

2015-01-01

Mitochondrial medicine provides a metabolic perspective on the pathology of conditions linked with inadequate oxidative phosphorylation. Dysfunction in the mitochondrial machinery can result in improper energy production, leading to cellular injury or even apoptosis. Clinical presentations are often subtle, so clinicians must have a high index of suspicion to make early diagnoses. Symptoms could include muscle weakness and pain, seizures, loss of motor control, decreased visual and auditory functions, metabolic acidosis, acute developmental regression, and immune system dysfunction. The 2013 Neurobiology of Disease in Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child Neurology Society, aimed to (1) describe accepted clinical phenotypes of mitochondrial disease produced from various mitochondrial mutations, (2) discuss contemporary understanding of molecular mechanisms that contribute to disease pathology, (3) highlight the systemic effects produced by dysfunction within the mitochondrial machinery, and (4) introduce current strategies that are being translated from bench to bedside as potential therapeutics. PMID:24916430

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty].

PubMed

Santana, Rafael Santos; Leite, Silvana Nair

2016-11-01

To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

[Clinical condition and therapy of bone diseases].

PubMed

Miura, Kohji; Oznono, Keiichi

2013-12-01

Skeletal dysplasia is the term which represents disorders including growth and differentiation of bone, cartilage and ligament. A lot of diseases are included, and new disorders have been added. However, the therapy of most bone diseases is less well-established. Achondroplasia, hypochondroplasia, and osteogenesis imperfecta are most frequent bone diseases. There is no curative treatment for these diseases, however, supportive therapies are available ; for example, growth-hormone therapy for achondroplasia and hypochondroplasia, and bisphosphonate therapy for osteogenesis imperfecta. In addition, enzyme replacement therapy for hypophosphatasia is now on clinical trial.

In the Clinic. Gastroesophageal Reflux Disease.

PubMed

Harnik, Ian G

2015-07-07

This issue provides a clinical overview of gastroesophageal reflux disease, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.

Outpatient nursing clinic for congenital heart disease patients: Copenhagen Transition Program.

PubMed

Berg, Selina Kikkenborg; Hertz, Pernille Grarup

2007-01-01

Adolescents with congenital heart disease need support transitioning from childhood to adulthood. To become independent, adolescents need to possess knowledge about the disease and how to handle life with congenital heart disease. Outpatient nursing clinics can address issues relevant for adolescents. Creating an environment in which worries and questions can be discussed better prepares adolescents to meet the struggles of living with congenital heart disease. The Copenhagen Transition Program was established in 2004. This outpatient nursing clinic was established by (1) defining the target group, (2) conducting a literature review, (3) collaborating with interdisciplinary colleagues, (4) scheduling visits to the transition-nursing clinic, (5) arranging clinic visits, (6) charting, and (7) testing and evaluating the clinic. Adolescents with congenital heart disease are invited to a consultation with a specially trained nurse, and it is the patients themselves who decide the content of the consultation. Topics such as knowledge about the disease, endocarditis, acute situations, nutrition, contraception, alcohol/drugs, smoking, physical activity, sleep/rest, and education may be discussed. Parents are asked not to participate.

Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease

PubMed Central

2010-01-01

Background Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II). Aim To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. Implementation and Results The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. Conclusions The Hunter disease eClinic

Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease.

PubMed

Al-Jasmi, Fatma; Moldovan, Laura; Clarke, Joe T R

2010-10-25

Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II). To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. The Hunter disease eClinic employs a CBT model providing the trainee with realistic

Glomerular disease: why is there a dearth of high quality clinical trials?

PubMed

Leaf, David E; Appel, Gerald B; Radhakrishnan, Jai

2010-08-01

There is a paucity of high quality clinical trials in glomerular disease, particularly in non-diabetic kidney disease. The aims of this review include quantifying the extent of this problem and exploring reasons for the scarcity of such trials in primary glomerular disease, with an emphasis on immunoglobulin A nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy in comparison with the more common diseases of diabetic nephropathy and lupus nephritis. Reasons for the dearth of high quality clinical trials in primary glomerular disease include (1) low prevalence of disease; (2) variability in clinical presentation; (3) variability in treatment response; (4) lack of consensus in definitions; (5) difficulty in recruiting patients; (6) high costs of randomized controlled trials; and (7) lack of collaborative efforts. To facilitate greater numbers of high quality clinical trials in glomerular disease, practice guidelines should establish common classification systems of disease and common clinical end points, industry and non-industry sponsored research should find common ground and work together toward advancing science, and national registries should be created to encourage collaborations across institutions and across nations.

Mucosal melanoma: a clinically and biologically unique disease entity.

PubMed

Carvajal, Richard D; Spencer, Sharon A; Lydiatt, William

2012-03-01

Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted.

Meningococcal disease, a clinical and epidemiological review.

PubMed

Batista, Rodrigo Siqueira; Gomes, Andréia Patrícia; Dutra Gazineo, Jorge Luiz; Balbino Miguel, Paulo Sérgio; Santana, Luiz Alberto; Oliveira, Lisa; Geller, Mauro

2017-11-01

Meningococcal disease is the acute infection caused by Neisseria meningitidis, which has humans as the only natural host. The disease is widespread around the globe and is known for its epidemical potential and high rates of lethality and morbidity. The highest number of cases of the disease is registered in the semi-arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional outbreaks, epidemics and sporadic cases occurring throughout the year, especially in the winter. The major epidemics of the disease occurred in Brazil in the 70's caused by serogroups A and C. Serogroups B, C and Y represent the majority of cases in Europe, the Americas and Australia. However, there has been a growing increase in serogroup W in some areas. The pathogen transmission happens for respiratory route (droplets) and clinically can lead to meningitis and sepsis (meningococcemia). The treatment is made with antimicrobial and supportive care. For successful prevention, we have some measures like vaccination, chemoprophylaxis and droplets' precautions. In this review, we have described and clarify clinical features of the disease caused by N. meningitidis regarding its relevance for healthcare professionals. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Predicting disease onset in clinically healthy people

PubMed Central

2016-01-01

Virtually all human disease is induced by oxidative stress. Oxidative stress, which is caused by toxic environmental exposure, the presence of disease, lifestyle choices, stress, chronic inflammation or combinations of these, is responsible for most disease. Oxidative stress from all sources is additive and it is the total oxidative stress from all sources that induces the onset of most disease. Oxidative stress leads to lipid peroxidation, which in turn produces Malondialdehyde. Serum malondialdehyde level is an additive parameter resulting from all sources of oxidative stress and, therefore, is a reliable indicator of total oxidative stress which can be used to predict the onset of disease in clinically asymptomatic individuals and to suggest the need for treatment that can prevent much human disease. PMID:28652846

Bridging the Gap between Research and Clinical Practice in Asymptomatic Alzheimer's Disease.

PubMed

Downing, A M; Yaari, R; Ball, D E; Selzler, K J; Devous, M D

2016-01-01

Due to the growing global health impact of Alzheimer's disease (AD), there is a greater need for interventions that prevent or delay the onset of clinical symptoms of this debilitating disease. Clinical trials for disease-modifying compounds in AD have shifted towards earlier stages in the spectrum of illness, including the stage prior to cognitive symptoms. A population of specific interest for clinical research includes individuals with evidence of Alzheimer's disease pathology who are asymptomatic (ADPa). The challenges and barriers regarding medical treatment of ADPa must be identified and addressed prior to the completion of a positive clinical trial in order to accelerate the translation of research findings to clinical practice. This report applies an existing public health impact model from Spencer and colleagues (2013) to evaluate the readiness of the clinical practice environment to treat ADPa individuals if a disease-modifying agent achieves approval. We contrast the current clinical practice environment with a potential future state through investigating the effectiveness, reach, feasibility, sustainability, and transferability of the practice of treating ADPa individuals.

Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

PubMed

Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

2015-04-15

The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifested. This literature search is performed because DiseaseConnect web server does not discriminate between pathologies emerging before, concomitantly or after infertility is manifested. Data show that different infertility etiologies not only share particular genes and/or molecular pathways with other pathologies but they have distinct clinical relationships with other diseases appearing after infertility is manifested. In particular, (1) testicular and high-grade prostate cancer in male infertility; (2) non-fatal stroke and endometrial cancer, and likely non-fatal coronary heart disease and ovarian cancer in polycystic ovary syndrome; (3) osteoporosis, psychosexual dysfunction, mood disorders and dementia in premature ovarian failure; (4) breast and ovarian cancer in carriers of BRCA1/2 mutations in diminished ovarian reserve; (5) clear cell and endometrioid histologic subtypes of invasive ovarian cancer, and likely low-grade serous invasive ovarian cancer, melanoma and non-Hodgkin lymphoma in endometriosis; and (6) endometrial and ovarian cancer in idiopathic infertility. The present data endorse the principle that the occurrence of a disease (in our case infertility) is non-random in the population and suggest that different infertility etiologies are genetically and clinically

[Clinical aspects of the Niigata Minamata disease].

PubMed

Shimohata, Takayoshi; Hirota, Koichi; Takahashi, Hitoshi; Nishizawa, Masatoyo

2015-01-01

The Minamata disease was discovered in the Minamata region, Kumamoto Prefecture, Japan, in 1956. Symptoms of this disease included cerebellar ataxia, sensory disturbance, narrowing of the visual field, and hearing and speech disturbances. In 1965, similar conditions were identified in persons living around the Agano River area, Niigata Prefecture, Japan and accordingly termed as the Niigata Minamata disease or the second Minamata disease. Both the diseases have been attributed to poisoning with methyl mercury that was generated during the production of acetaldehyde using mercury as a catalyst. The discharged methyl mercury accumulated in fishes and shellfishes and caused poisoning on consumption. This review discusses the history, clinical presentation including atypical forms, and autopsy findings of the Niigata Minamata disease. In addition, it highlights the problems about criteria for official recognition and the therapeutic trial for this disease.

A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases.

PubMed

Bernheim, Adam; McLoud, Theresa

2017-05-01

The purpose of this article is to review the clinical and imaging findings associated with eosinophilic lung diseases. The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders that have an association with tissue or peripheral eosinophilia. These diseases have varied clinical presentations and may be associated with several other abnormalities. Characteristic imaging findings are often detected with chest radiography, and CT best shows parenchymal abnormalities. The integration of clinical, radiologic, and pathologic findings facilitates diagnosis and directs appropriate treatment.

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PubMed

von Coelln, Rainer; Shulman, Lisa M

2016-12-01

Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

The clinical utility of health-related quality of life screening in a pediatric inflammatory bowel disease clinic.

PubMed

Ryan, Jamie L; Mellon, Michael W; Junger, Katherine W F; Hente, Elizabeth A; Denson, Lee A; Saeed, Shehzad A; Hommel, Kevin A

2013-11-01

Adjusting to symptom flares, treatment regimens, and side effects places youth with inflammatory bowel disease (IBD) at increased risk for emotional and behavioral problems and adverse disease outcomes. Implementation of psychosocial screening into clinical practice remains a challenge. This study examines the clinical utility of health-related quality of life (HRQOL) screening in predicting disease outcome and healthcare utilization. One hundred twelve youth of 7 to 18 years diagnosed with IBD and their parents. Youth completed standardized measures of HRQOL and depression. Parents completed a proxy report of HRQOL. Pediatric gastroenterologists provided the Physician Global Assessment. Families were recruited from a pediatric gastroenterology clinic. Retrospective chart reviews examined disease outcome and healthcare utilization for 12 months after baseline measurement. Linear regressions, controlling for demographic and disease parameters, revealed that baseline measurement of youth and parent proxy-reported HRQOL predicted the number of IBD-related hospital admissions, gastroenterology clinic visits, emergency department visits, psychology clinic visits, telephone contacts, and pain management referrals over the next 12 months. Disease outcome was not significant. Lower HRQOL was predictive of increased healthcare utilization among youth with IBD. Regular HRQOL screening may be the impetus to providing better case management and allocating resources based on ongoing care needs and costs. Proactive interventions focused on patients with poor HRQOL may be an efficient approach to saving on healthcare costs and resource utilization.

Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

PubMed

Ilus, T; Kaukinen, K; Virta, L J; Huhtala, H; Mäki, M; Kurppa, K; Heikkinen, M; Heikura, M; Hirsi, E; Jantunen, K; Moilanen, V; Nielsen, C; Puhto, M; Pölkki, H; Vihriälä, I; Collin, P

2014-02-01

Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully. © 2014 John Wiley & Sons Ltd.

[Lyme disease--clinical manifestations and treatment].

PubMed

Stock, Ingo

2016-05-01

Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

Nutritional value of pupae versus larvae of Tenebrio molitor (Coleoptera: Tenebrionidae) as food for rearing Podisus maculiventris (Heteroptera: Pentatomidae)

USDA-ARS?s Scientific Manuscript database

Factitious prey are often more suitable for use in mass production of beneficial insects than natural prey. Life table analysis yielded demographic parameter values that indicate Tenebrio molitor (L.) pupae are promising as factitious prey to mass produce Podisus maculiventris (Say) and are more sui...

Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.

PubMed

Tortelli, Rosanna; Seripa, Davide; Panza, Francesco; Solfrizzi, Vincenzo; Logroscino, Giancarlo

2016-01-01

Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted. The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification. © 2016 S. Karger AG, Basel.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

The perpetrators of medical child abuse (Munchausen Syndrome by Proxy) - A systematic review of 796 cases.

PubMed

Yates, Gregory; Bass, Christopher

2017-10-01

Little is known about the perpetrators of medical child abuse (MCA) which is often described as "Munchausen's syndrome by proxy" or "factitious disorder imposed on another". The demographic and clinical characteristics of these abusers have yet to be described in a sufficiently large sample. We aimed to address this issue through a systematic review of case reports and series in the professional literature. A systematic search for case reports and series published since 1965 was undertaken using MEDLINE, Web of Science and EMBASE. 4100 database records were screened. A supplementary search was then conducted using GoogleScholar and reference lists of eligible studies. Our search yielded a total sample of 796 perpetrators: 309 from case reports and 487 from case series. Information extracted included demographic and clinical characteristics, in addition to methods of abuse and case outcomes. Nearly all abusers were female (97.6%) and the victim's mother (95.6%). Most were married (75.8%). Mean caretaker age at the child's presentation was 27.6 years. Perpetrators were frequently reported to be in healthcare-related professions (45.6%), to have had obstetric complications (23.5%), or to have histories of childhood maltreatment (30%). The most common psychiatric diagnoses recorded were factitious disorder imposed on self (30.9%), personality disorder (18.6%), and depression (14.2%). From the largest analysis of MCA perpetrators to date, we provide several clinical recommendations. In particular, we urge clinicians to consider mothers with a personal history of childhood maltreatment, obstetric complications, and/or factitious disorder at heightened risk for MCA. Longitudinal studies are required to establish the true prognostic value of these factors as our method may have been vulnerable to publication bias. Copyright © 2017. Published by Elsevier Ltd.

Atrophia maculosa varioliformis cutis.

PubMed

Marks, V J; Miller, O F

1986-07-01

We describe a case of atrophia maculosa varioliformis cutis (AMVC), a rare form of idiopathic facial macular atrophy. A biopsy revealed only a depression in the epidermis, probably caused by loss of dermal collagen. Because AMVC may be confused with scarring, and factitial disease may be suggested, it is important that this condition be recognized by the physician.

Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

PubMed

Spies, Petra E; Verbeek, Marcel M; Sjogren, Magnus J C; de Leeuw, Frank-Erik; Claassen, Jurgen A H R

2014-01-01

Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. The AD biomarkers CSF amyloid β42, amyloid β40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. No association between CSF amyloid β42, amyloid β40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

PubMed

Elston, Marianne S; Sehgal, Shekhar; Du Toit, Stephen; Yarndley, Tania; Conaglen, John V

2016-09-01

Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 μg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. A tertiary endocrine service in Hamilton, New Zealand. The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

Experiences from an interprofessional student-assisted chronic disease clinic.

PubMed

Frakes, Kerrie-Anne; Brownie, Sharon; Davies, Lauren; Thomas, Janelle; Miller, Mary-Ellen; Tyack, Zephanie

2014-11-01

Faced with significant health and workforce challenges in the region, the Central Queensland Health Service District (CQHSD) commenced a student-assisted clinical service. The Capricornia Allied Health Partnership (CAHP) is an interprofessional clinical placement program in which pre-entry students from exercise physiology, nutrition and dietetics, occupational therapy, pharmacy, podiatry and social work are embedded in a collaborative chronic disease service delivery model. The model coordinates multiple student clinical placements to: address service delivery gaps for previously underserved people with chronic disease in need of early intervention and management; provide an attractive clinical placement opportunity for students that will potentially lead to future recruitment success, and demonstrate leadership in developing future health workforce trainees to attain appropriate levels of interprofessional capacity. The CAHP clinic commenced student placements and client services in February 2010. This report provides early evaluative information regarding student experiences included self-reported changes in practice.

Applications of Doppler ultrasound in clinical vascular disease

NASA Technical Reports Server (NTRS)

Barnes, R. W.; Hokanson, D. E.; Sumner, D. S.; Strandness, D. E., Jr.

1975-01-01

Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

PubMed Central

2016-01-01

We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

Recent clinical trials in valvular heart disease.

PubMed

Kiss, Daniel; Anwaruddin, Saif

2017-07-01

With widespread adoption of transcatheter aortic valve replacement, there has been a change in the approach to management of valvular heart disease. New interest has taken hold in transcatheter therapies for valvular heart disease, as well as research into pathophysiology and progression of disease. Additionally, several key trials have further refined our understanding of surgical management of valvular heart disease. This review will elucidate recent clinical trial data leading to changes in practice. There have been several landmark trials expanding the indications for transcatheter aortic valve replacement. Additionally, although still early, trials are beginning to demonstrate the feasibility and safety of transcatheter mitral valves. Options for transcatheter management of right-sided valvular disease continue to evolve, and these are areas of active investigation. The emergence of novel therapies for valvular heart disease has expanded the management options available, allowing physicians to better individualize treatment of patients with valvular heart disease. This review will focus on the recent (within 2 years) trials in this field of interest.

Creating an effective clinical registry for rare diseases

PubMed Central

D’Agnolo, Hedwig MA; Kievit, Wietske; Andrade, Raul J; Karlsen, Tom Hemming; Wedemeyer, Heiner

2015-01-01

The exposure of clinicians to patients with rare gastrointestinal diseases is limited. This hurts clinical studies, which impedes accumulation of scientific knowledge on the natural disease course, treatment outcomes and prognosis in these patients. An excellent method to detect patterns on an aggregate level that would not be possible to discover in individual cases, is a registry study. This paper aims to describe a template to create a successful international registry for rare diseases. We focus mainly on rare hepatic diseases, but lessons from this paper serve other fields in medicine, as well. PMID:27403298

[Circular RNA in human disease and their potential clinic significance].

PubMed

Chen, Yonghua; Li, Cheng; Tan, Chunlu; Mai, Gang; Liu, Xubao

2017-02-10

Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

Genotyping of Mycobacterium intracellulare isolates and clinical characteristics of lung disease.

PubMed

Kim, S-Y; Lee, S-T; Jeong, B-H; Park, H Y; Jeon, K; Kim, J-W; Shin, S J; Koh, W-J

2013-05-01

Variable number of tandem repeats (VNTR) loci were recently identified in Japanese isolates of Mycobacterium intracellulare. We hypothesised that some mycobacterial genotypes are more virulent than others, resulting in particular genotypes being associated with disease phenotype and progression. To evaluate the VNTR loci of M. intracellulare in clinical isolates from Korean patients, and investigate the association between mycobacterial genotype and disease phenotype and progression. In total, 70 M. intracellulare clinical isolates were genotyped using 16 M. intracellulare VNTR loci. VNTR typing showed strong discriminatory power and genetic diversity for molecular epidemiological studies of M. intracellulare. In a phylogenetic tree, the M. intracellulare clinical isolates were divided into two clusters (A and B). Cluster A was observed more frequently (77%) than Cluster B; however, there was no association between the clinical characteristics, disease progression, drug susceptibility and clusters based on VNTR genotyping. VNTR typing could be used for epidemiological studies of M. intracellulare lung disease; however, no association was found between the specific VNTR genotypes of M. intracellulare and the clinical characteristics of Korean patients.

Munchausen Syndrome by Proxy: A Family Affair.

ERIC Educational Resources Information Center

Mehl, Albert L.; And Others

1990-01-01

The article reports on a case of Munchausen syndrome by proxy in which chronic illicit insulin was administered to a one-year-old child by her mother. Factitious illnesses continued despite psychiatric intervention. Retrospective review of medical records suggested 30 previous episodes of factitious illness within the family. (DB)

Norrie disease: extraocular clinical manifestations in 56 patients.

PubMed

Smith, Sharon E; Mullen, Thomas E; Graham, Dionne; Sims, Katherine B; Rehm, Heidi L

2012-08-01

Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. Copyright © 2012 Wiley Periodicals, Inc.

Monitoring clinical progression with mitochondrial disease biomarkers

PubMed Central

Steele, Hannah E; Horvath, Rita; Lyon, Jon J; Chinnery, Patrick F

2017-01-01

Abstract Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies. PMID:28969370

Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

PubMed

González García, A; Patier de la Peña, J L; Ortego Centeno, N

2017-03-01

Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic findings.

PubMed

Pousa-Martínez, María; Alfageme, Fernando; González de Domingo, María Antonia; Suárez-Masa, Dolores; Calvo, Marta; Roustán, Gastón

2017-11-15

Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease characterized by skin lesions separated from the lesions of the gastrointestinal tract. The diagnosis of MCD is essentially histological,showing noncaseating granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD with vulvar involvement and clinical, histopathological, and ultrasonographic findings of this disease.

A Review of the Centers for Disease Control and Prevention's Guidelines for the Clinical Laboratory Diagnosis of Lyme Disease.

PubMed

Miraglia, Caterina M

2016-12-01

The purpose of this paper is to review information regarding the current guidelines for the clinical laboratory diagnosis of Lyme disease as set forth by the Centers for Disease Control and Prevention (CDC) to chiropractic physicians and to discuss the clinical utility of this testing. The CDC's website was reviewed to determine what their current recommendations are for the clinical laboratory testing of Lyme disease. The CDC's established guidelines recommend the use of a 2-tiered serologic testing algorithm for the evaluation of patients with suspected Lyme disease. This review provides doctors of chiropractic with information to remain current with the CDC's recommended guidelines for Lyme disease testing because patients may present to their office with the associated signs and symptoms of Lyme disease.

Periodontal disease in diabetic patients - clinical and histopathological aspects.

PubMed

Corlan Puşcu, Dorina; Ciuluvică, Radu Constantin; Anghel, Andreea; Mălăescu, Gheorghe Dan; Ciursaş, Adina Nicoleta; Popa, Gabriel Valeriu; Agop Forna, Doriana; Busuioc, Cristina Jana; Siloşi, Izabela

2016-01-01

Periodontal disease is one of the most frequent diseases affecting people all over the world. The relation between periodontal disease and diabetes mellitus raised the interest both of dentists and doctors treating metabolic diseases, as the two conditions influence one another. In our study, we analyzed a number of 75 patients with diabetes mellitus and periodontal disease that presented to the medical consultory for conditions of the dental maxillary system. The clinical study showed that periodontal disease and diabetes may affect young adults as well, still this pathological association more frequently appears after the age of 50. The disease was identified especially in the women living in urban area. The clinical examination of the dental maxillary system identified the presence of gingival ulcerations, dental calculus, gingival bleeding, radicular leftovers with anfractuous margins, fixed prostheses with an inappropriate cervical adjustment. Of the systemic diseases associated to periodontal disease and diabetes mellitus, there was observed that 66.66% of the patients also suffered from cardiovascular diseases (high blood pressure, ischemic cardiopathy, heart failure), and 37.33% suffered from obesity. The histopathological and immunohistochemical tests highlighted the presence of an inflammatory chronic, intense reaction, mainly formed of lymphocytes, plasmocytes, macrophages and granulocytes, heterogeneously disseminated and alteration of the structure of marginal and superficial periodontium. The inflammatory reaction in the patients with periodontal disease and diabetes was more intense than in the patients with periodontal disease without diabetes.

Clinic Attendance of Youth With Sickle Cell Disease on Hydroxyurea Treatment.

PubMed

Ingerski, Lisa M; Arnold, Trisha L; Banks, Gabrielle; Porter, Jerlym S; Wang, Winfred C

2017-07-01

The objective of this study is to describe rates of clinic attendance of youth with sickle cell disease prescribed hydroxyurea and examine potential demographic and medical factors related to consistent clinic attendance. Participants included 148 youth diagnosed with sickle cell disease and prescribed hydroxyurea during a single calendar year. Clinic attendance and potential demographic and medical factors related to attendance were extracted via systematic retrospective medical chart review. Youth attended 90.3% of scheduled appointments and 85.1% of youth attended at least 80% of scheduled clinic appointments during the study window. Adjusting for other factors, multivariate analysis revealed families with fewer children in the household, families with private insurance, youth experiencing fever, and youth not experiencing pain during the calendar year were more likely to consistently attend clinic visits. Adherence to clinic appointments is critical to optimizing health outcomes for youth with sickle cell disease and integral for adequate monitoring of youth prescribed hydroxyurea, in particular. Findings may aid providers in appropriately identifying possible barriers to clinic attendance to develop attendance promotion interventions.

[Malabsorption is a leading clinical sign of small bowel disease].

PubMed

Parfenov, A I; Krums, L M

The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.

Impact of live interactive teledermatology on diagnosis, disease management, and clinical outcomes.

PubMed

Lamel, Sonia; Chambers, Cindy J; Ratnarathorn, Mondhipa; Armstrong, April W

2012-01-01

To assess the impact of live interactive teledermatology consultations on changes in diagnosis, disease management, and clinical outcomes. We conducted a retrospective analysis of 1500 patients evaluated via live interactive teledermatology between 2003 and 2005 at the University of California, Davis. We compared diagnoses and treatment plans between the referring physicians and the teledermatologists. Patients with 2 or more teledermatology visits within a 1-year period were assessed for changes in clinical outcomes. Academic medical center with an established teledermatology program since 1996. Medical records were evaluated for 1500 patients who underwent live interactive teledermatology consultation. Patients seen for more than 1 teledermatology visit were included in the clinical outcome assessment. Live interactive teledermatology consultation. Changes in diagnosis, disease management, and clinical outcome. Compared with diagnoses and treatment plans from referring physicians, the 1500 live interactive teledermatology consultations resulted in changes in diagnosis in 69.9% of patients and changes in disease management in 97.7% of patients. Among 313 patients with at least 2 teledermatology visits within 1 year, clinical improvement was observed in 68.7% of patients. Multivariate analysis showed that changes in diagnosis (P = .01), changes in disease management (P < .001), and the number of teledermatology visits (P < .001) were significantly associated with improved clinical outcomes. Live interactive teledermatology consultations result in changes in diagnosis and disease management in most consultations. The numbers of live interactive teledermatology visits and changes in diagnosis and disease management are significantly associated with improved clinical outcomes.

Gaucher disease: clinical profile and therapeutic developments.

PubMed

Cox, Timothy M

2010-12-06

Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster. Human β-glucocerebrosidase was originally obtained from placenta and the Genzyme Corporation (Allston, MA) subsequently developed a recombinant product. After purification, the enzyme is modified to reveal terminal mannose residues which facilitate selective uptake of the protein, imiglucerase (Cerezyme(®)), in macrophage-rich tissues. The unprecedented success of Cerezyme has attracted fierce competition: two biosimilar agents, velaglucerase-alfa, VPRIV(®) (Shire Human Genetic Therapies, Dublin, Ireland) and taliglucerase-alfa (Protalix, Carmiel, Israel), are now approved or in late-phase clinical development as potential 'niche busters'. Oral treatments have advantages over biological agents for disorders requiring lifelong therapy and additional stratagems which utilize small, orally active molecules have been introduced; these include two chemically distinct compounds which inhibit uridine diphosphate glucose: N-acylsphingosine glucosyltransferase, the first step in the biosynthesis of glucosylceramide - a key molecular target in Gaucher disease and other glycosphingolipidoses. Academic and commercial enterprises in biotechnology have combined strategically to expand the therapeutic repertoire in Gaucher disease. The innovative potential of orphan drug legislation has been realized - with prodigious rewards for companies embracing its humanitarian precepts. In the era

Gaucher disease: clinical profile and therapeutic developments

PubMed Central

Cox, Timothy M

2010-01-01

Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster. Human β-glucocerebrosidase was originally obtained from placenta and the Genzyme Corporation (Allston, MA) subsequently developed a recombinant product. After purification, the enzyme is modified to reveal terminal mannose residues which facilitate selective uptake of the protein, imiglucerase (Cerezyme®), in macrophage-rich tissues. The unprecedented success of Cerezyme has attracted fierce competition: two biosimilar agents, velaglucerase-alfa, VPRIV® (Shire Human Genetic Therapies, Dublin, Ireland) and taliglucerase-alfa (Protalix, Carmiel, Israel), are now approved or in late-phase clinical development as potential ‘niche busters’. Oral treatments have advantages over biological agents for disorders requiring lifelong therapy and additional stratagems which utilize small, orally active molecules have been introduced; these include two chemically distinct compounds which inhibit uridine diphosphate glucose: N-acylsphingosine glucosyltransferase, the first step in the biosynthesis of glucosylceramide – a key molecular target in Gaucher disease and other glycosphingolipidoses. Academic and commercial enterprises in biotechnology have combined strategically to expand the therapeutic repertoire in Gaucher disease. The innovative potential of orphan drug legislation has been realized – with prodigious rewards for companies embracing its humanitarian precepts. In the

A 90-year-old man with factious disorder: Separating fact from fiction.

PubMed

Amladi, Anjani K; DePry, Dwayne R

2018-07-01

Objective Factitious disorders are known to exist in the medical community but are not commonly diagnosed in clinical practice. The majority of the literature on factitious disorder comes from case reports or case series. This particular case is unusual because it describes a patient who initially presented with purely physical complaints, but over time, the symptoms transitioned into predominantly psychiatric concerns. This case describes the patient's unique presentation and is followed by a discussion of the management of factitious disorder. Methods The patient was seen during the course of an inpatient psychiatric hospitalization. Electronic chart review was conducted, and information from each prior hospitalization was gathered between the dates of first initial documented presentation available in the electronic record in 1995 to most recent hospitalization in 2017. Results The patient still continues to present to the emergency department. Upon each presentation, staff work to objectively assess his complaints to be sure that there is no true underlying medical emergency. There is also a focus on providing non-judgmental, supportive, and compassionate care. Conclusion This case highlights the importance of corroborating objective findings with the patient's subjective reports gathered during a history and physical, and to recognize that patients with this disorder can present to any specialty. Thus, the collaboration between specialties is critical in the care of these patients to minimize unnecessary, costly, and sometimes dangerous interventions.

Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer's Disease Task Force.

PubMed

Cummings, J; Fox, N; Vellas, B; Aisen, P; Shan, G

2018-01-01

Disease-modifying therapies are urgently needed for the treatment of Alzheimer's disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. A survey of members of the EU/US Alzheimer's Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design

A study on specialist or special disease clinics based on big data.

PubMed

Fang, Zhuyuan; Fan, Xiaowei; Chen, Gong

2014-09-01

Correlation analysis and processing of massive medical information can be implemented through big data technology to find the relevance of different factors in the life cycle of a disease and to provide the basis for scientific research and clinical practice. This paper explores the concept of constructing a big medical data platform and introduces the clinical model construction. Medical data can be collected and consolidated by distributed computing technology. Through analysis technology, such as artificial neural network and grey model, a medical model can be built. Big data analysis, such as Hadoop, can be used to construct early prediction and intervention models as well as clinical decision-making model for specialist and special disease clinics. It establishes a new model for common clinical research for specialist and special disease clinics.

Comparing clinical profiles in Alzheimer's disease and Parkinson's disease dementia.

PubMed

Farlow, Martin R; Schmitt, Frederick; Aarsland, Dag; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2013-01-01

Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies. This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1]. Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47) and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58) were higher in AD; PDD patients were more impaired in the language (0.23) and praxis (0.34) domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14) and improvement on the NPI-10 (0.11) compared with patients with PDD. Differing patterns of impairment occur in AD and PDD.

[Clinical and morphological variants of diverticular disease in colon].

PubMed

Levchenko, S V; Lazebnik, L B; Potapova, V B; Rogozina, V A

2013-01-01

Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The art and science of choosing efficacy endpoints for rare disease clinical trials.

PubMed

Cox, Gerald F

2018-04-01

An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, defined as how a patient, feels, functions, or survives, in at least one adequate and well-controlled pivotal study conducted according to Good Clinical Practice. In some cases, full regulatory approval can occur using a validated surrogate biomarker, while accelerated, or provisional, approval can occur using a biomarker that is likely to predict clinical benefit. Rare disease studies are small by necessity and require the use of endpoints with large effect sizes to demonstrate statistical significance. Understanding the quantitative factors that determine effect size and its impact on powering the study with an adequate sample size is key to the successful choice of endpoints. Interpreting the clinical meaningfulness of an observed change in an efficacy endpoint can be justified by statistical methods, regulatory precedence, and clinical context. Heterogeneous diseases that affect multiple organ systems may be better accommodated by endpoints that assess mean change across multiple endpoints within the same patient rather than mean change in an individual endpoint across all patients. © 2018 Wiley Periodicals, Inc.

[Augmentin in the clinical picture of infectious diseases].

PubMed

Gracheva, N M; Petrova, M S; Avakov, A A; Bobovnikova, V T

1992-09-01

Augmentin is a new combination manufactured by Smith Kline Beecham (Great Britain). It is composed of amoxycillin and clavulanic acid and has antibacterial activity. Augmentin was used in clinical trials in the therapy of 50 adult patients with suppurations after surgical operations on the organs of the abdominal cavity, general staphylococcal infections, pneumonia and prophylactically during the preoperative period. It was also used in the treatment of 30 children patients with bronchopulmonary affections and inflammatory otorhinolaryngological diseases. The clinical trials were performed in the Clinic of Infectious Diseases of the N. G. Gabrichevskiĭ Moscow Research Institute of Epidemiology and Microbiology. For comparison ampicillin was used in the trials. Augmentin was shown to be an efficient formulation with antibacterial activity which could be successfully used in the parenteral therapy of severe affections due to organisms sensitive to it. In the treatment of the children patients with pneumonia augmentin by its therapeutic efficacy proved to be superior to ampicillin. The tolerance of augmentin was good.

Munchausen's syndrome: a medico-legal dilemma.

PubMed

Mydlo, J H; Macchia, R J; Kanter, J L

1997-07-01

In his or her life-long career, the physician will eventually encounter a patient with factitious disorder, or Munchausen's syndrome. We discuss two patients complaining of renal colic that were identified as having Munchausen's syndrome. We review the literature to identify certain aspects of the disease and to discuss the medical and legal implications for the treating physician and hospital.

Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

PubMed Central

Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

2016-01-01

Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

Idiopathic Canalicular Inflammatory Disease: New Disease Description of Clinical Patterns, Investigations, Management, and Outcomes.

PubMed

Ali, Mohammad Javed

2018-01-25

The objective of this perspective is to present a separate disease description of "idiopathic canalicular inflammatory disease" and outline the diagnostic criteria and early experiences with its investigations and management. Retrospective case series of 44 canaliculi of 22 eyes of 11 patients presenting at a tertiary care Dacryology service over a period of 2 years with typical clinical patterns of inflammatory canaliculitis and its outcomes were studied. All the patients underwent microbiological work-up with culture and sensitivity, dacryoendoscopy imaging, serial Fourier domain ocular coherence tomography, and collagen vascular profiles. Stages in the evolution of the disease were studied. All patients were treated initially with topical steroids followed by punctal dilatation and placement of mini-monoka stents. Five patients in addition had a small biopsy from the inflamed portion of the vertical canaliculus. Stents were extubated at 6 weeks. Forty-four canaliculi were diagnosed to have idiopathic canalicular inflammatory disease during the study period. There was a female preponderance (81.8%, 9/11) and the mean age at presentation was 57 years. All patients presented with unilateral epiphora without any discharge, pain, or swelling. Collagen vascular profiles and screening for autoimmune diseases were negative. Clinical picture ranged from stages 1 to 5, consisting of edema, progressive centripetal vascularization, pouting of vascularized mucosa, membrane formation, and progressive scarring. The presentation begins in 1 eye and usually involves the other eye at a mean of 6 months. Ocular coherence tomography and dacryoendoscopy were of adjunctive value in the diagnosis. Histopathological examination was suggestive of a chronic inflammation. All patients had relentless progression to end-stage disease, although delayed significantly by steroids and monoka intubation. Idiopathic canalicular inflammatory disease has a distinct and typical clinical behavior and

The Infectious Diseases Society of America emerging infections network: bridging the gap between clinical infectious diseases and public health.

PubMed

Pillai, Satish K; Beekmann, Susan E; Santibanez, Scott; Polgreen, Philip M

2014-04-01

In 1995, the Centers for Disease Control and Prevention granted a Cooperative Agreement Program award to the Infectious Diseases Society of America to develop a provider-based emerging infections sentinel network, the Emerging Infections Network (EIN). Over the past 17 years, the EIN has evolved into a flexible, nationwide network with membership representing a broad cross-section of infectious disease physicians. The EIN has an active electronic mail conference (listserv) that facilitates communication among infectious disease providers and the public health community, and also sends members periodic queries (short surveys on infectious disease topics) that have addressed numerous topics relevant to both clinical infectious diseases and public health practice. The article reviews how the various functions of EIN contribute to clinical care and public health, identifies opportunities to further link clinical medicine and public health, and describes future directions for the EIN.

Clinical significance of mycobacterial genotyping in Mycobacterium avium lung disease in Korea.

PubMed

Kim, S-Y; Lee, S-T; Jeong, B-H; Jeon, K; Kim, J-W; Shin, S J; Koh, W-J

2012-10-01

A recent study in Japan found that mycobacterial genotyping was associated with disease progression and susceptibility to certain drugs in Mycobacterium avium lung disease. However, it is not known whether this association is true in other populations. To investigate the association between mycobacterial genotype, clinical characteristics and the progression of M. avium lung disease in Korean patients. A total of 102 M. avium clinical isolates were genotyped using M. avium tandem repeats-variable number of tandem repeats (MATR-VNTR). MATR-VNTR typing demonstrated a high discriminatory power and genetic diversity for molecular epidemiological studies of M. avium. In the phylogenetic tree, the M. avium clinical isolates were divided into three major clusters: A, B and C. Cluster A was observed most frequently (64/102, 63%), whereas cluster C was found in a minor proportion of the isolates (8/102, 8%). However, there was no association between the clinical characteristics, disease progression and drug susceptibility and the phylogenetic tree based on VNTR genotyping. MATR-VNTR genotyping may be useful for epidemiological studies of M. avium lung disease; however, no association was found between the specific VNTR genotypes of M. avium and the clinical characteristics of Korean patients.

Clinical features of Crohn disease concomitant with ankylosing spondylitis

PubMed Central

Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian

2016-01-01

Abstract Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS. We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison. Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (−) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73–0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = −0.73 to −0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = −0.81 to −0.91, P < 0.05). Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected. PMID:27428240

Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

PubMed

Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos

2018-04-01

Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.

Clinical features of hemorrhoidal disease in renal transplant recipients.

PubMed

Tallarita, T; Gurrieri, C; Cappellani, A; Corona, D; Gagliano, M; Giuffrida, G; Caglià, P; Fiamingo, P; Giaquinta, A; Sinagra, N; Zerbo, D; Virzì, G; Veroux, P; Veroux, M

2010-05-01

Hemorrhoidal disease is a frequent cause of morbidity among the general population with a reported incidence of 4.4%, but little is known about its incidence and clinical features in kidney transplant recipients. Among 116 patients who had undergone kidney transplantation and were evaluated for hemorrhoidal disease, 82 had no hemorrhoids (70.6%), 28 (24%) had grade I hemorrhoids, and 6 (5.4%) had grade II hemorrhoids at the pretransplantation evaluation. Twenty-seven out of 116 recipients (22.4%) developed grade III or IV hemorrhoids after transplantation and underwent surgery. Hemorrhoidal disease was more frequent in patients with a pretransplantation history of hemorrhoids, with a rapid weight increase in the posttransplantation period, or who were aged between 30 and 50 years. Immunosuppressive therapy may play an important role in the worsening of hemorrhoidal disease among kidney transplant recipients. A prompt diagnosis and surgical treatment, whenever necessary, is mandatory for patients with clinical signs of worsening of hemorrhoids. Copyright (c) 2010 Elsevier Inc. All rights reserved.

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-10-01

A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Rethinking dry eye disease: a perspective on clinical implications.

PubMed

Bron, Anthony J; Tomlinson, Alan; Foulks, Gary N; Pepose, Jay S; Baudouin, Christophe; Geerling, Gerd; Nichols, Kelly K; Lemp, Michael A

2014-04-01

Publication of the DEWS report in 2007 established the state of the science of dry eye disease (DED). Since that time, new evidence suggests that a rethinking of traditional concepts of dry eye disease is in order. Specifically, new evidence on the epidemiology of the disease, as well as strategies for diagnosis, have changed the understanding of DED, which is a heterogeneous disease associated with considerable variability in presentation. These advances, along with implications for clinical care, are summarized herein. The most widely used signs of DED are poorly correlated with each other and with symptoms. While symptoms are thought to be characteristic of DED, recent studies have shown that less than 60% of subjects with other objective evidence of DED are symptomatic. Thus the use of symptoms alone in diagnosis will likely result in missing a significant percentage of DED patients, particularly with early/mild disease. This could have considerable impact in patients undergoing cataract or refractive surgery as patients with DED have less than optimal visual results. The most widely used objective signs for diagnosing DED all show greater variability between eyes and in the same eye over time compared with normal subjects. This variability is thought to be a manifestation of tear film instability which results in rapid breakup of the tearfilm between blinks and is an identifier of patients with DED. This feature emphasizes the bilateral nature of the disease in most subjects not suffering from unilateral lid or other unilateral destabilizing surface disorders. Instability of the composition of the tears also occurs in dry eye disease and shows the same variance between eyes. Finally, elevated tear osmolarity has been reported to be a global marker (present in both subtypes of the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically, osmolarity has been shown to be the best single metric for diagnosis of DED and is directly related to

Design and Evaluation of a Bacterial Clinical Infectious Diseases Ontology

PubMed Central

Gordon, Claire L.; Pouch, Stephanie; Cowell, Lindsay G.; Boland, Mary Regina; Platt, Heather L.; Goldfain, Albert; Weng, Chunhua

2013-01-01

With antimicrobial resistance increasing worldwide, there is a great need to use automated antimicrobial decision support systems (ADSSs) to lower antimicrobial resistance rates by promoting appropriate antimicrobial use. However, they are infrequently used mostly because of their poor interoperability with different health information technologies. Ontologies can augment portable ADSSs by providing an explicit knowledge representation for biomedical entities and their relationships, helping to standardize and integrate heterogeneous data resources. We developed a bacterial clinical infectious diseases ontology (BCIDO) using Protégé-OWL. BCIDO defines a controlled terminology for clinical infectious diseases along with domain knowledge commonly used in hospital settings for clinical infectious disease treatment decision-making. BCIDO has 599 classes and 2355 object properties. Terms were imported from or mapped to Systematized Nomenclature of Medicine, Unified Medical Language System, RxNorm and National Center for Bitechnology Information Organismal Classification where possible. Domain expert evaluation using the “laddering” technique, ontology visualization, and clinical notes and scenarios, confirmed the correctness and potential usefulness of BCIDO. PMID:24551353

The Role of Biomarkers in Clinical Trials for Alzheimer Disease

PubMed Central

Thal, Leon J.; Kantarci, Kejal; Reiman, Eric M.; Klunk, William E.; Weiner, Michael W.; Zetterberg, Henrik; Galasko, Douglas; Praticò, Domenico; Griffin, Sue; Schenk, Dale; Siemers, Eric

2007-01-01

Biomarkers are likely to be important in the study of Alzheimer disease (AD) for a variety of reasons. A clinical diagnosis of Alzheimer disease is inaccurate even among experienced investigators in about 10% to 15% of cases, and biomarkers might improve the accuracy of diagnosis. Importantly for the development of putative disease-modifying drugs for Alzheimer disease, biomarkers might also serve as indirect measures of disease severity. When used in this way, sample sizes of clinical trials might be reduced, and a change in biomarker could be considered supporting evidence of disease modification. This review summarizes a meeting of the Alzheimer’s Association’s Research Roundtable, during which existing and emerging biomarkers for AD were evaluated. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or ligands binding to amyloid plaque are discussed. Additionally, biochemical biomarkers in blood or cerebrospinal fluid are assessed. Currently appropriate uses of biomarkers in the study of Alzheimer disease, and areas where additional work is needed, are discussed. PMID:16493230

Estrogens and Coronary Artery Disease: New Clinical Perspectives.

PubMed

Meyer, M R; Barton, M

2016-01-01

In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER), which like the "classical" receptors ERα and ERβ is highly abundant in the cardiovascular system. Here, we discuss the role of estrogen receptors in the pathogenesis of coronary artery disease and review natural and synthetic ligands of estrogen receptors as well as their effects in physiology, on cardiovascular risk factors, and atherosclerotic vascular disease. Data from preclinical and clinical studies using nonselective compounds activating GPER, which include selective estrogen receptor modulators such as tamoxifen or raloxifene, selective estrogen receptor downregulators such as Faslodex™ (fulvestrant/ICI 182,780), vitamin B3 (niacin), green tea catechins, and soy flavonoids such as genistein or resveratrol, strongly suggest that activation of GPER may afford therapeutic benefit for primary and secondary prevention in patients with or at risk for coronary artery disease. Evidence from preclinical studies suggest similar efficacy profiles for selective small molecule GPER agonists such as G-1 which are devoid of uterotrophic activity. Further clinical research in this area is warranted to provide opportunities for future cardiovascular drug development. © 2016 Elsevier Inc. All rights reserved.

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

PubMed

Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

2018-01-01

Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Hyperthyroidism

PubMed Central

2016-01-01

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves’ disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves’ disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. PMID:27038492

Huntington’s Disease Clinical Trials Corner: February 2018

PubMed Central

Rodrigues, Filipe B.; Wild, Edward J.

2018-01-01

In the second edition of the Huntington’s Disease Clinical Trials Corner we list all currently registered and ongoing clinical trials, summarise the top-line results of the recently-announced IONIS-HTTRX trial (NCT02519036), expand on Wave Life Sciences’ PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846), and cover one recently finished trial: the FIRST-HD deutetrabenazine trial (NCT01795859). PMID:29480210

Professional challenges and opportunities in clinical microbiology and infectious diseases in Europe.

PubMed

Read, Robert C; Cornaglia, Giuseppe; Kahlmeter, Gunnar

2011-05-01

The two closely linked specialties of clinical microbiology and infectious diseases face important challenges. We report the consensus of clinical microbiologists and infectious disease physicians assembled by the European Society for Clinical Microbiology and Infectious Diseases. Both specialties have different training requirements in different European countries and are not universally recognised as professions. The specialties are rapidly evolving as they adapt to the changing demands within hospital practice, including the need to deal with emerging infections, rapidly increasing internationalisation, and immigration. Clinical microbiology needs to develop and master technological advances such as laboratory automation and an avalanche of new methods for rapid diagnostics. Simultaneously, the pressure for concentration, amalgamation, and out-sourcing of laboratory services is ever-increasing. Infectious disease physicians have to meet the professional challenge of subspecialisation and the continual need to find new niches for their skills. Despite these challenges, each of these specialties continues to thrive in Europe and will enjoy important opportunities over the next few years. The recently formed European Centre for Disease Prevention and Control in Stockholm, Sweden, will increase demands in areas of surveillance of infectious diseases and antimicrobial resistance on both specialties. Copyright © 2011 Elsevier Ltd. All rights reserved.

The clinical spectrum of late-onset Alexander disease: a systematic literature review.

PubMed

Balbi, Pietro; Salvini, Silvana; Fundarò, Cira; Frazzitta, Giuseppe; Maestri, Roberto; Mosah, Dibo; Uggetti, Carla; Sechi, GianPietro

2010-12-01

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

The Infectious Diseases Society of America Emerging Infections Network: Bridging the Gap Between Clinical Infectious Diseases and Public Health

PubMed Central

Pillai, Satish K.; Beekmann, Susan E.; Santibanez, Scott; Polgreen, Philip M.

2015-01-01

In 1995, the Centers for Disease Control and Prevention granted a Cooperative Agreement Program award to the Infectious Diseases Society of America to develop a provider-based emerging infections sentinel network, the Emerging Infections Network (EIN). Over the past 17 years, the EIN has evolved into a flexible, nationwide network with membership representing a broad cross-section of infectious disease physicians. The EIN has an active electronic mail conference (listserv) that facilitates communication among infectious disease providers and the public health community, and also sends members periodic queries (short surveys on infectious disease topics) that have addressed numerous topics relevant to both clinical infectious diseases and public health practice. The article reviews how the various functions of EIN contribute to clinical care and public health, identifies opportunities to further link clinical medicine and public health, and describes future directions for the EIN. PMID:24403542

Design of clinical trials of gene therapy in Parkinson disease.

PubMed

Lewis, Travis B; Standaert, David G

2008-01-01

No current therapy for Parkinson disease has been shown to slow or reverse the progressive course of the disease. As a departure from traditional treatments, gene therapy approaches provide a new hope for realizing this long-sought goal; but before they can be widely employed for use in patients, they must first be submitted to the rigorous safety and efficacy standards of the clinical trial. Some of the challenges of gene therapy clinical trial design are similar to those in studies of conventional pharmacological agents and include addressing the heterogeneity of the disease, the need for clinical and surrogate endpoints, and the issue of distinguishing "symptomatic" from "neuroprotective" effects. Gene therapy trials also raise the issues of the risks of viral therapy, issues of dose-response, the need for sham surgery, and the long duration of risks and benefits. We conclude that the most feasible designs are for those treatments that are expected to produce a rapid improvement in directly observable symptoms. Trials of agents which are expected to produce only a slowing of progression and not a reversal of the disease course are likely to take much longer and will require the development of methods to assess quality of life and other non-motor aspects of the disease.

Clinical Prediction Models for Cardiovascular Disease: Tufts Predictive Analytics and Comparative Effectiveness Clinical Prediction Model Database.

PubMed

Wessler, Benjamin S; Lai Yh, Lana; Kramer, Whitney; Cangelosi, Michael; Raman, Gowri; Lutz, Jennifer S; Kent, David M

2015-07-01

Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease, there are numerous CPMs available although the extent of this literature is not well described. We conducted a systematic review for articles containing CPMs for cardiovascular disease published between January 1990 and May 2012. Cardiovascular disease includes coronary heart disease, heart failure, arrhythmias, stroke, venous thromboembolism, and peripheral vascular disease. We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. Seven hundred seventeen (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions, including 215 CPMs for patients with coronary artery disease, 168 CPMs for population samples, and 79 models for patients with heart failure. There are 77 distinct index/outcome pairings. Of the de novo models in this database, 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. There is an abundance of CPMs available for a wide assortment of cardiovascular disease conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood. © 2015 American Heart Association, Inc.

Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

PubMed Central

Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

2014-01-01

The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

PubMed Central

Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

2011-01-01

Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

Munchausen syndrome: Playing sick or sick player

PubMed Central

Prakash, Jyoti; Das, R. C.; Srivastava, K.; Patra, P.; Khan, S. A.; Shashikumar, R.

2014-01-01

Munchausen syndrome is rare factitious disorder which entails frequent hospitalization, pathological lying and intentional production of symptoms for sick role. Management requires collateral history taking, sound clinical approach, exclusion of organicity and addressing psychological issues. A case which presented with unusual symptoms of similar dimension is discussed here. The case brings out finer nuances in evaluation and management of this entity. PMID:25535450

Clinical utility of sympathetic blockade in cardiovascular disease management.

PubMed

Park, Chan Soon; Lee, Hae-Young

2017-04-01

A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management. Expert commentary: Chronic sympathetic nervous system activation is related to several cardiovascular diseases mediated by various pathways. Advancement in measuring sympathetic activity makes visualizing noninvasively and evaluating the activation level even in single fibers possible. Evidence suggests that sympathetic blockade still has a role in managing hypertension and controlling the heart rate in atrial fibrillation. For ischemic heart disease, beta-adrenergic receptor antagonists have been considered a milestone drug to control symptoms and prevent long-term adverse effects, although its clinical implication has become less potent in the era of successful revascularization. Owing to pathologic involvement of sympathetic nervous system activation in heart failure progression, sympathetic blockade has proved its value in improving the clinical course of patients with heart failure.

Relationships among clinical measures of periodontal disease and their associations with systemic markers.

PubMed

Beck, James D; Offenbacher, Steven

2002-12-01

Recent investigations of the relationship between periodontitis and systemic disease require that periodontal disease also must be thought of as a disease process that is an exposure for a systemic disease or condition (outcome), rather than as the outcome itself. When viewing periodontal disease as an exposure, investigators must consider the clinical, microbiological, and inflammatory components of periodontitis that potentially convey risk for the systemic outcome of interest, which may or may not be the same as those associated with the assessments used to define tooth-based disease. Another important consideration is the temporal relationship between the exposure and the outcome of interest. To explore which definitions of periodontal disease or clustering of clinical signs are important with regards to systemic exposure to inflammatory stress, we examined the relationship between clinical periodontal disease measures and 2 systemic inflammatory markers of increased risk for cardiovascular disease: serum soluble intercellular adhesion molecule (sICAM), which is a measure of vascular stress and serum C-reactive protein (CRP), which is a measure of hepatic acute-phase response. The Dental Arteriosclerosis Risk in Communities (ARIC) study, a cross-sectional study of the relationship between periodontal disease and cardiovascular disease, forms the basis for the examples used in this investigation. Our findings demonstrated that while attachment loss, probing depth, (PD) and bleeding on probing (BOP) are individually associated with sICAM and CRP, only BOP remains significant for sICAM when all 3 are in the model and, for CRP, only PD remains significant. Both of these clinical parameters were more robust in estimating the degree of systemic inflammation than traditional classifications of mild, moderate, and severe periodontitis or other measures of disease severity such as attachment loss. When selecting a definition of "systemic periodontitis" (periodontal

Can we Predict Disease Course with Clinical Factors?

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Golovics, Petra A; Lakatos, Peter L

2018-01-01

The disease phenotype at diagnosis and the disease course of Crohn's disease (CD) and ulcerative colitis (UC) show remarkable heterogeneity across patients. This review aims to summarize the currently available evidence on clinical and some environmental predictive factors, which clinicians should evaluate in the everyday practice together with other laboratory and imaging data to prevent disease progression, enable a more personalized therapy, and avoid negative disease outcomes. In recent population-based epidemiological and referral cohort studies, the evolution of disease phenotype of CD and UC varied significantly. Most CD and severe UC patients still require hospitalization or surgery/colectomy during follow-up. A change in the natural history of inflammatory bowel diseases (IBD) with improved outcomes in parallel with tailored positioning of aggressive immunomodulator and biological therapy has been suspected. According to the currently available literature, it is of major importance to refer IBD cases at risk for adverse disease outcomes as early during the disease course as possible. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical study of an outbreak of Legionnaire's disease in Alcoy, Southeastern Spain.

PubMed

Fernández, J A; López, P; Orozco, D; Merino, J

2002-10-01

The aim of this study was to identify the clinical features of Legionnaires' disease, sudden outbreaks of which demand a quick and flexible clinical approach, particularly with regard to diagnosis and therapy. A prospective and comparative study based on a clinical protocol was performed during an outbreak of Legionnaires' disease in Alcoy, Spain. The outbreak was environmental in origin, linked to cooling towers. Data about epidemiological and clinical features, blood chemistry values, radiological and microbiological findings, and characteristics related to the clinical course of Legionnaires' disease were obtained for 357 patients admitted to hospital with community-acquired pneumonia (177 with Legionella pneumonia). Patients with Legionnaires' disease were younger (mean age, 65.3+/-16.5 years) and more likely to be smokers compared with patients with other types of pneumonia (28.8% vs. 11.1%; P<0.01). Moreover, they had not been admitted to any hospital because of pneumonia in the previous year. Patients with Legionnaires' disease had higher fever, more severe headache, and less expectoration as well as lower sodium blood levels (mean, 132.6+/-4.8 mmol/l vs. 135.7 mmol/l; P<0.01). Radiological studies also showed that fewer patients with Legionnaires' disease had pleural effusion (9% vs. 19.4% of those with non- Legionella pneumonia). The presence of headache, high fever, hyponatremia, scanty or null expectoration, and current cigarette smoking provides physicians with important clues for a high suspicion of Legionella pneumonia before the results of confirmatory laboratory tests are available.

Ethical Considerations for Clinical Trials in Inflammatory Bowel Disease

PubMed Central

Becker, Samuel; Siegler, Mark

2014-01-01

Although advancements in the field of inflammatory bowel disease (IBD) include effective therapies for many patients with Crohn’s disease and ulcerative colitis, there remains a large unmet need, and there is a large number of investigational agents in the pipeline. Drug development through clinical trials is critical to understanding the safety and efficacy of new therapies in the affected human population, and the need for ethical trial design is of the utmost importance. This paper explores the ethical issues of clinical trials in IBD, focusing on placebo-controlled trials, vulnerable patients, exposure to monoclonal antibodies, globalization of trials, and surgical advances. PMID:24799837

Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

PubMed Central

Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

2015-01-01

Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met

Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

PubMed

Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

2016-09-01

See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

Seronegative celiac disease: Shedding light on an obscure clinical entity.

PubMed

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J; Ruggeri, Eugenio; Paterini, Paola; De Giorgio, Roberto

2016-09-01

Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

77 FR 14805 - Clinical Laboratory Improvement Advisory Committee, Centers for Disease Control and Prevention...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Clinical Laboratory Improvement Advisory Committee, Centers for Disease Control and Prevention: Notice of Charter..., that the Clinical Laboratory Improvement Advisory Committee, Centers for Disease Control and Prevention...

Clinical Data Warehouse: An Effective Tool to Create Intelligence in Disease Management.

PubMed

Karami, Mahtab; Rahimi, Azin; Shahmirzadi, Ali Hosseini

Clinical business intelligence tools such as clinical data warehouse enable health care organizations to objectively assess the disease management programs that affect the quality of patients' life and well-being in public. The purpose of these programs is to reduce disease occurrence, improve patient care, and decrease health care costs. Therefore, applying clinical data warehouse can be effective in generating useful information about aspects of patient care to facilitate budgeting, planning, research, process improvement, external reporting, benchmarking, and trend analysis, as well as to enable the decisions needed to prevent the progression or appearance of the illness aligning with maintaining the health of the population. The aim of this review article is to describe the benefits of clinical data warehouse applications in creating intelligence for disease management programs.

Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji.

PubMed

Engelman, Daniel; Mataika, Reapi L; Ah Kee, Maureen; Donath, Susan; Parks, Tom; Colquhoun, Samantha M; Carapetis, Jonathan R; Kado, Joseph H; Steer, Andrew C

2017-08-01

Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group. Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

Clinical application of next-generation sequencing for Mendelian diseases.

PubMed

Jamuar, Saumya Shekhar; Tan, Ene-Choo

2015-06-16

Over the past decade, next-generation sequencing (NGS) has led to an exponential increase in our understanding of the genetic basis of Mendelian diseases. NGS allows for the analysis of multiple regions of the genome in one single reaction and has been shown to be a cost-effective and efficient tool in investigating patients with Mendelian diseases. More recently, NGS has been successfully deployed in the clinics, with a reported diagnostic yield of ~25 %. However, recommendations on clinical implementation of NGS are still evolving with numerous key challenges that impede the widespread use of genetics in everyday medicine. These challenges include when to order, on whom to order, what type of test to order, and how to interpret and communicate the results, including incidental findings, to the patient and family. In this review, we discuss these challenges and suggest guidelines on implementing NGS in the routine clinical workflow.

Predicting clinical diagnosis in Huntington's disease: An imaging polymarker

PubMed Central

Daws, Richard E.; Soreq, Eyal; Johnson, Eileanoir B.; Scahill, Rachael I.; Tabrizi, Sarah J.; Barker, Roger A.; Hampshire, Adam

2018-01-01

Objective Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real‐life clinical diagnosis in HD. Method A multivariate machine learning approach was applied to resting‐state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross‐group comparisons between preHD and controls, and within the preHD group in relation to “estimated” and “actual” proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy. Results Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models. Interpretation We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials. Ann Neurol 2018;83:532–543 PMID:29405351

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

PubMed Central

Santiago, Jose A.; Bottero, Virginie; Potashkin, Judith A.

2017-01-01

A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD. PMID:29255414

Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

PubMed Central

Overington, Jeff D.; Huang, Yao C.; Abramson, Michael J.; Brown, Juliet L.; Goddard, John R.; Bowman, Rayleen V.; Fong, Kwun M.

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care. PMID:25478199

Clinical experience with infliximab therapy in 100 patients with Crohn's disease.

PubMed

Farrell, R J; Shah, S A; Lodhavia, P J; Alsahli, M; Falchuk, K R; Michetti, P; Peppercorn, M A

2000-12-01

The aim of this study was to assess our clinical experience with infliximab, a monoclonal antitumor necrosis factor antibody, following its approval for treatment of refractory Crohn's disease (CD). We followed 100 consecutive patients with CD (53 women and 47 men; mean age, 41 yr) who received a total of 233 infliximab (5 mg/kg) infusions. Adverse events were noted and clinical response assessed every 2 wk for 6 months after each infusion using the Harvey Bradshaw Index (HBI) for active disease, the Perianal Disease Activity Index (PDAI) for fistulous disease, and steroid withdrawal rates for steroid-sparing efficacy. Indications for therapy were active disease (n = 57), perianal fistulous disease (n = 33), and steroid dependency (n = 10). Significant infusion reactions occurred in 16 patients (6.9% of infusions) including anaphylactic shock in one patient. Fourteen patients experienced infectious adverse events, 13 of whom were on concurrent steroids. Sixty percent of patients with active disease experienced > or = 50% HBI reduction at 2 wk; mean duration of response, 8.2 wk. Three of 26 first-time nonresponders with active disease (12%) responded to a second infusion. Sixty-nine percent of patients with fistulous disease experienced >50% reduction in their PDAI at 2 wk; mean duration of response, 10.9 wk. Four of 10 steroid-dependent patients (40%) discontinued steroid therapy, one of whom recommenced steroid therapy at 24 wk. Our clinical response rates mirror the efficacy reported in the controlled trials for active and fistulous disease. Steroid-sparing efficacy was seen in 40% of steroid-dependent patients. Concurrent steroids did not reduce the risk of significant infusion reactions (6.9%), but did increase the risk of infections.

Measurement of leukocyte rheology in vascular disease: clinical rationale and methodology. International Society of Clinical Hemorheology.

PubMed

Wautier, J L; Schmid-Schönbein, G W; Nash, G B

1999-01-01

The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.

Insulin resistance in clinical and experimental alcoholic liver disease

PubMed Central

Carr, Rotonya M.; Correnti, Jason

2015-01-01

Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of health care dollars annually. Since the advent of the obesity epidemic, insulin resistance and diabetes have become common clinical findings in patients with ALD; and the development of insulin resistance predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin-sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease. PMID:25998863

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

PubMed Central

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Podometrics as a Potential Clinical Tool for Glomerular Disease Management.

PubMed

Kikuchi, Masao; Wickman, Larysa; Hodgin, Jeffrey B; Wiggins, Roger C

2015-05-01

Chronic kidney disease culminating in end-stage kidney disease is a major public health problem costing in excess of $40 billion per year with high morbidity and mortality. Current tools for glomerular disease monitoring lack precision and contribute to poor outcome. The podocyte depletion hypothesis describes the major mechanisms underlying the progression of glomerular diseases, which are responsible for more than 80% of cases of end-stage kidney disease. The question arises of whether this new knowledge can be used to improve outcomes and reduce costs. Podocytes have unique characteristics that make them an attractive monitoring tool. Methodologies for estimating podocyte number, size, density, glomerular volume and other parameters in routine kidney biopsies, and the rate of podocyte detachment from glomeruli into urine (podometrics) now have been developed and validated. They potentially fill important gaps in the glomerular disease monitoring toolbox. The application of these tools to glomerular disease groups shows good correlation with outcome, although data validating their use for individual decision making is not yet available. Given the urgency of the clinical problem, we argue that the time has come to focus on testing these tools for application to individualized clinical decision making toward more effective progression prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Smart Technology in Lung Disease Clinical Trials.

PubMed

Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

2016-01-01

This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. Published by Elsevier Inc.

Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated.

PubMed

Almeida, Beverley; Campanilho-Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A; Wedderburn, Lucy R; Nistala, Kiran

2015-09-01

The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P-CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P-CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met the other 3 criteria. Incorporating PGA as

The prevalence and clinical characteristics of punding in Parkinson's disease.

PubMed

Spencer, Ashley H; Rickards, Hugh; Fasano, Alfonso; Cavanna, Andrea E

2011-03-01

Punding (the display of stereotyped, repetitive behaviors) is a relatively recently discovered feature of Parkinson's disease (PD). Little is known about the prevalence and clinical characteristics of punding in PD. In this review, four large scientific databases were comprehensively searched for literature in relation to punding prevalence and clinical correlates in the context of PD. Prevalence was found to vary greatly (between 0.34 to 14%), although there were large disparities in study populations, assessment methods, and criteria. We observed an association between punding, dopaminergic medications, and impulse control disorder. Other characteristics, which may be more common among punders, include a higher severity of dyskinesia, younger age of disease onset, longer disease duration, and male gender. More research in large clinical datasets is required in many areas before conclusions are drawn. The pathophysiology behind the punding phenomenon is also poorly understood at present, rendering it difficult to develop targeted therapy. The current mainstay of treatment is the reduction in the dose of dopaminergic medications, the evidence for other suggested therapies being purely empirical.

Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

PubMed

Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

2016-01-06

Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design.

Profile of breast diseases at a self-referral clinic in Ghana.

PubMed

Clegg-Lamptey, J N A; Aduful, H K; Yarney, J; Adu-Aryee, N A; Vanderpuye, V; Kyereh, M; Nkansah, A; Edwin, A

2009-03-01

Breast cancer is a common malignancy in Ghana, and many patients are referred with advanced disease and long duration of symptoms. To determine the spectrum of breast disease diagnosed through patient self-referral in Ghana. A breast clinic, where patients could walk in without referral, was started in the Korle Bu Teaching Hospital in 2001. A team of surgeons, radiation oncologists, oncology nurses, a clinical psychologist and a clinical pharmacist sat in conference once a week to see and discuss self-referred patients. Seven hundred and forty eight patients, mean age 38.6 (range 8-85) years, were seen during a four-year period. There were 741 females and seven males. The main complaints were pain 450 (50.2%), lump 257 (28.7%) and nipple discharge 62 (8.3%). Fifty (5.6%) came for check-up; 139 (18.6%) had more than one complaint. The mean (S.D.) duration of symptoms was; for nipple discharge 14.1 (10.5) months, lump 11.9 (7.7) months, and pain 11.3 (8.9) months. The main diagnoses were: Normal breasts 192 (27.7%), mastalgia 135 (18.1%), fibroadenosis 114 (15.2%), fibroadenomas 84 (11.2%), breast cancer 58 (7.8%), suspected breast cancer 25 (3.3%), galactorrhea 9 (1.2%), mastitis 8 (1.1%), musculoskeletal pain 8 (1.1%), duct ectasia 8 (1.1%), mondor's disease 7 (0.94%) and recurrent breast cancer 6 (0.8%). In patients with breast cancer, 42 (66%) had advanced disease, 6 (9.4%) had recurrent disease and 4 (63%) had metastatic disease. The number of self-referrals, detected breast cancers and duration of symptoms justify the need for self-referral clinics in Ghana.

Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

PubMed

Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

2017-09-01

Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

Clinical and Molecular Features of POLG-Related Mitochondrial Disease

PubMed Central

Stumpf, Jeffrey D.; Saneto, Russell P.; Copeland, William C.

2013-01-01

The inability to replicate mitochondrial genomes (mtDNA) by the mitochondrial DNA polymerase (pol γ) leads to a subset of mitochondrial diseases. Many mutations in POLG, the gene that encodes pol γ, have been associated with mitochondrial diseases such as myocerebrohepatopathy spectrum (MCHS) disorders, Alpers-Huttenlocher syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), and progressive external ophthalmoplegia (PEO). This chapter explores five important topics in POLG-related disease: (1) clinical symptoms that identify and distinguish POLG-related diseases, (2) molecular characterization of defects in polymerase activity by POLG disease variants, (3) the importance of holoenzyme formation in disease presentation, (4) the role of pol γ exonuclease activity and mutagenesis in disease and aging, and (5) novel approaches to therapy and avoidance of toxicity based on primary research in pol γ replication. PMID:23545419

Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options

PubMed Central

Tanna, Preena; Strauss, Rupert W; Fujinami, Kaoru; Michaelides, Michel

2017-01-01

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4. Significant advances have been made over the last 10 years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and genotypic characteristics of the disease, conventional and novel imaging findings, current knowledge of animal models and pathogenesis, and the multiple avenues of intervention being explored. PMID:27491360

Implementation and evaluation of Parkinson disease management in an outpatient clinical pharmacist-run neurology telephone clinic.

PubMed

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.

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

PubMed Central

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-01-01

Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

PubMed

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-09-01

This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

Hyperthyroidism.

PubMed

De Leo, Simone; Lee, Sun Y; Braverman, Lewis E

2016-08-27

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influenza and other respiratory viruses: standardizing disease severity in surveillance and clinical trials.

PubMed

Rath, Barbara; Conrad, Tim; Myles, Puja; Alchikh, Maren; Ma, Xiaolin; Hoppe, Christian; Tief, Franziska; Chen, Xi; Obermeier, Patrick; Kisler, Bron; Schweiger, Brunhilde

2017-06-01

Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed. Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0-18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79). Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.

Stem cells in bone diseases: current clinical practice.

PubMed

Beyth, Shaul; Schroeder, Josh; Liebergall, Meir

2011-01-01

Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. Stem cell therapy offers new options for bone conditions, both acquired and inherited. There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.

Clinical Holistic Medicine: Chronic Infections and Autoimmune Diseases

PubMed Central

Ventegodt, Søren; Merrick, Joav

2005-01-01

The consciousness-based (holistic) medical toolbox might be useful in general practice and in cases of recurrent infections and chronic infection or inflammation. From our clinical experiences, there is hope for improvement from a number of diseases caused by disorders affecting the regulation of the immune system when the physician includes the holistic medical approach.Our scientific understanding of the connection between consciousness and cellular order is still limited. Consciousness-based holistic medicine removes (as explained by the holistic process theory of healing) the “blockages” in the tissues of the body and facilitates function and informational exchange of the cells of the body. Many blockages and repressed feelings in an area would imply “noise and disturbances” on the level of intercellular communications, which in turn means major difficulties for the cells of the immune system. For this they are totally dependent on the body information system, which the holistic treatment aims to recover. Processing the blockages increases the coherence of the cells and organism, thus increasing the intercellular flow of information in the area and thus strengthening the immune defense and healing the disease. The area of clinical holistic medicine is going through a rapid development and the toolbox of consciousness-based medicine is available for dealing with many diseases arising from disturbances in the regulation of the immune system. Holistic medicine has yet to be better explained scientifically and our proposed holistic cures have yet to be documented clinically. We invite the medical community to cooperate on this important challenge. PMID:15759081

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial.

PubMed

Lazzerini, Marzia; Martelossi, Stefano; Magazzù, Giuseppe; Pellegrino, Salvatore; Lucanto, Maria Cristina; Barabino, Arrigo; Calvi, Angela; Arrigo, Serena; Lionetti, Paolo; Lorusso, Monica; Mangiantini, Francesca; Fontana, Massimo; Zuin, Giovanna; Palla, Gabriella; Maggiore, Giuseppe; Bramuzzo, Matteo; Pellegrin, Maria Chiara; Maschio, Massimo; Villanacci, Vincenzo; Manenti, Stefania; Decorti, Giuliana; De Iudicibus, Sara; Paparazzo, Rossella; Montico, Marcella; Ventura, Alessandro

2013-11-27

Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Assessment of the Siksika chronic disease nephropathy-prevention clinic

PubMed Central

Ward, David R.R.; Novak, Ellen; Scott-Douglas, Nairne; Brar, Sony; White, Melvin; Hemmelgarn, Brenda R.

2013-01-01

Objective To determine if a community-based multifactorial intervention clinic led by a nurse practitioner would improve management of First Nations people at risk of developing chronic kidney disease. Design Qualitative descriptive study. Setting A nephropathy-prevention clinic in Siksika Nation, Alta. Participants First Nations people with diabetes, hypertension, or dyslipidemia who were referred to the clinic. Main outcome measures Changes in blood pressure (BP), hemoglobin A1c, and low-density lipoprotein levels, as well as in use of antiplatelet therapy, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications, and statin therapy. Results Members of the Siksika Nation were treated according to clinical practice guidelines. A total of 78 patients had at least 2 visits to the clinic and were included in this analysis (61.5% were women; mean age 56 years). Among those initially above target, a significant reduction was achieved in mean hemoglobin A1c (0.96%; P < .01), systolic BP (15.84 mm Hg; P < .05), diastolic BP (7.16 mm Hg; P < .001), and low-density lipoprotein (0.62 mmol/L; P < .01) levels. There was a significant increase in the proportion of patients with clinical indications who were treated with acetylsalicylic acid (42.4%; P < .01), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications (35.9%; P < .01), or statin therapy (35.9%; P < .01). Conclusion A community-based, nurse practitioner–led clinic can improve many clinically relevant factors in patients at risk of developing chronic kidney disease. Studies have shown that achieving treatment targets is associated with a reduced risk of early death and cardiovascular events; the effect in the First Nations population on these hard clinical end points remains to be determined. PMID:23341675

National Priority Setting of Clinical Practice Guidelines Development for Chronic Disease Management.

PubMed

Jo, Heui-Sug; Kim, Dong Ik; Oh, Moo-Kyung

2015-12-01

By November 2013, a total of 125 clinical practice guidelines (CPGs) have been developed in Korea. However, despite the high burden of diseases and the clinical importance of CPGs, most chronic diseases do not have available CPGs. Merely 83 CPGs are related to chronic diseases, and only 40 guidelines had been developed in the last 5 yr. Considering the rate of the production of new evidence in medicine and the worsening burden from chronic diseases, the need for developing CPGs for more chronic diseases is becoming increasingly pressing. Since 2011, the Korean Academy of Medical Sciences and the Korea Centers for Disease Control and Prevention have been jointly developing CPGs for chronic diseases. However, priorities have to be set and resources need to be allocated within the constraint of a limited funding. This study identifies the chronic diseases that should be prioritized for the development of CPGs in Korea. Through an objective assessment by using the analytic hierarchy process and a subjective assessment with a survey of expert opinion, high priorities were placed on ischemic heart disease, cerebrovascular diseases, Alzheimer's disease and other dementias, osteoarthritis, neck pain, chronic kidney disease, and cirrhosis of the liver.

Planning Future Clinical Trials for Machado-Joseph Disease.

PubMed

Saute, Jonas Alex Morales; Jardim, Laura Bannach

2018-01-01

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant multiple neurological systems degenerative disorder caused by a CAG repeat expansion at ATXN3 gene. Only a few treatments were evaluated in randomized clinical trials (RCT) in SCA3/MJD patients, with a lack of evidence for both disease-modifying and symptomatic therapies. The present chapter discuss in detail major methodological issues for planning future RCT for SCA3/MJD. There are several potential therapies for SCA3/MJD with encouraging preclinical results. Route of treatment, dosage titration and potential therapy biomarkers might differ among candidate drugs; however, the core study design and protocol will be mostly the same. RCT against placebo group is the best study design to test a disease-modifying therapy; the same cannot be stated for some symptomatic treatments. Main outcomes for future RCT are clinical scales: the Scale for the Assessment and Rating of ataxia (SARA) is currently the instrument of choice to prove efficacy of disease-modifying or symptomatic treatments against ataxia, the most important disease feature. Ataxia quantitative scales or its composite scores can be used as primary outcomes to provide preliminary evidence of efficacy in phase 2 RCT, due to a greater sensitivity to change. Details regarding eligibility criteria, randomization, sample size estimation, duration and type of analysis for both disease modifying and symptomatic treatment trials, were also discussed. Finally, a section anticipates the methodological issues for testing novel drugs when an effective treatment is already available. We conclude emphasizing four points, the first being the need of RCT for a number of different aims in the care of SCA3/MJD. Due to large sample sizes needed to warrant power, RCT for disease-modifying therapies should be multicenter enterprises. There is an urge need for surrogate markers validated for several drug classes. Finally, engagement of at

Epidemiology of clinical trials of medicines in respiratory diseases in Europe and Italy.

PubMed

Bodini, Roberta; Santus, Pierachille; Di Marco, Fabiano; Aliberti, Stefano; Centanni, Stefano; Blasi, Francesco; Rizzi, Andrea; Recchia, Giuseppe

2017-04-01

Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy. Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country. In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%). Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical potentials of human pluripotent stem cells in lung diseases

PubMed Central

2014-01-01

Lung possesses very limited regenerative capacity. Failure to maintain homeostasis of lung epithelial cell populations has been implicated in the development of many life-threatening pulmonary diseases leading to substantial morbidity and mortality worldwide, and currently there is no known cure for these end-stage pulmonary diseases. Embryonic stem cells (ESCs) and somatic cell-derived induced pluripotent stem cells (iPSCs) possess unlimited self-renewal capacity and great potential to differentiate to various cell types of three embryonic germ layers (ectodermal, mesodermal, and endodermal). Therapeutic use of human ESC/iPSC-derived lung progenitor cells for regeneration of injured or diseased lungs will have an enormous clinical impact. This article provides an overview of recent advances in research on pluripotent stem cells in lung tissue regeneration and discusses technical challenges that must be overcome for their clinical applications in the future. PMID:24995122

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

PubMed Central

Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A.; Kern, Volker D.; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T.; Romero, Klaus

2017-01-01

Abstract Given the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed‐effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was –3.16 (90% confidence interval [CI] = –0.96 to –5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. PMID:28749580

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

PubMed

Prus, Višnja; Kardum, Željka

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient’s general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Playing patient, playing doctor: Munchausen syndrome, clinical S/M, and ruptures of medical power.

PubMed

Fisher, Jill A

2006-01-01

This article deploys sadomasochism as a framework for understanding medical practice on an institutional level. By examining the case of the factitious illness Munchausen syndrome, this article analyzes the operations of power in the doctor-patient relationship through the trope of role-playing. Because Munchausen syndrome causes a disruption to the dyadic relationship between physicians and patients, a lens of sadomasochism highlights dynamics of power in medical practice that are often obscured in everyday practice. Specifically, this article illustrates how classification and diagnosis are concrete manifestations of the mobilization of medical power.

Lung cancer and chronic obstructive pulmonary disease: From a clinical perspective

PubMed Central

Dai, Jie; Yang, Ping; Cox, Angela; Jiang, Gening

2017-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges. COPD confers a higher risk for lung cancer development, but available chemopreventive measures remain rudimentary. Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD. COPD-associated lung cancer presents distinct clinical features. Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival. In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population. PMID:28061470

Oxidative stress treatment for clinical trials in neurodegenerative diseases.

PubMed

Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

2011-01-01

Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease

PubMed Central

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P.; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C.; Goate, Alison

2017-01-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. PMID:29091718

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

PubMed

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos

2017-11-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study.

PubMed

Adler, Charles H; Beach, Thomas G; Hentz, Joseph G; Shill, Holly A; Caviness, John N; Driver-Dunckley, Erika; Sabbagh, Marwan N; Sue, Lucia I; Jacobson, Sandra A; Belden, Christine M; Dugger, Brittany N

2014-07-29

Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard. Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard. Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia. Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 years' duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced. This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%. © 2014 American Academy of Neurology.

Personality in Parkinson's disease: Clinical, behavioural and cognitive correlates.

PubMed

Santangelo, Gabriella; Piscopo, Fausta; Barone, Paolo; Vitale, Carmine

2017-03-15

Affective disorders and personality changes have long been considered pre-motor aspects of Parkinson's disease (PD). Many authors have used the term "premorbid personality" to define distinctive features of PD patients' personality characterized by reduced exploration of new environmental stimuli or potential reward sources ("novelty seeking") and avoidance behaviour ("harm avoidance") present before motor features. The functional correlates underlying the personality changes described in PD, implicate dysfunction of meso-cortico-limbic and striatal circuits. As disease progresses, the imbalance of neurotransmitter systems secondary to degenerative processes, along with dopamine replacement therapy, can produce a reversal of behaviours and an increase in reward seeking, laying the foundations for the emergence of the impulse control disorders. Personality disorders can be interpreted, therefore, as the result of individual susceptibility arising from intrinsic degenerative processes and individual personality features, in combination with extrinsic factors such as lifestyle, PD motor dysfunction and drug treatment. For a better understanding of personality disorders observed in PD and their relationship with the prodromal stage of the disease, prospective clinical studies are needed that correlate different personality profiles with other disease progression markers. Here, we review previous studies investigating the clinical, cognitive and behavioural correlates of personality traits in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The clinical use of structural MRI in Alzheimer disease

PubMed Central

Frisoni, Giovanni B.; Fox, Nick C.; Jack, Clifford R.; Scheltens, Philip; Thompson, Paul M.

2010-01-01

Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment. PMID:20139996

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

Alzheimer disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer disease.

PubMed

Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Deramecourt, V; Lebert, F; Amouyel, P; Pasquier, F

2009-02-01

Vascular dementia (VaD) and Alzheimer disease with cerebrovascular disease (AD+CVD) are the leading causes of dementia after Alzheimer disease alone (AD). Little is known about the progression of either VaD or AD+CVD. The aim of this study was to compare demographic features, cognitive decline and survival of patients with VaD, AD+CVD and AD alone attending a memory clinic. This study included 970 patients who were followed at the Lille-Bailleul memory clinic, France. Cognitive functions were measured with the Mini Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). Survival rate was analysed with a left-truncated Cox model. Analyses were adjusted for age, sex, education, hypertension, diabetes and baseline MMSE and DRS. Of 970 patients, 141 had VaD, 663 AD alone and 166 AD+CVD. The latter were significantly older than AD or VaD patients at onset (71 (SD 7) vs 69 (9) and 68 (9) years, p = 0.01) and at first visit (75 (6) vs 73 (8) and 72 (8) years, p = 0.0002). Baseline MMSE and DRS evaluations were highest for VaD compared with AD alone or AD+CVD patients (p<0.006). Cognitive decline during follow-up was slowest for VaD, intermediate for AD+CVD and fastest for AD alone (p = 0.03). After adjustment, compared with AD patients, mortality risk was similar for those with VaD (relative mortality risk (RR) = 0.7 (0.5 to 1.1)) and tended to be lower for AD+CVD (RR = 0.7 (0.5 to 1.0)). The shorter the delay between first symptoms and first visit, the longer patients survived. This clinical cohort study shows that patients with VaD, AD+CVD and AD present different characteristics at baseline and during follow-up, and underlines the need to distinguish between them.

Clinical disease registries in acute myocardial infarction.

PubMed

Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

2014-06-26

Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

PubMed

Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

2017-11-01

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice.

PubMed

Anderson, Jaclyn; Caplan, Liron; Yazdany, Jinoos; Robbins, Mark L; Neogi, Tuhina; Michaud, Kaleb; Saag, Kenneth G; O'Dell, James R; Kazi, Salahuddin

2012-05-01

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice. The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations. Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures. We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings. Copyright © 2012 by the American College of Rheumatology.

Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.

PubMed

Zhang, Yanhang; Barocas, Victor H; Berceli, Scott A; Clancy, Colleen E; Eckmann, David M; Garbey, Marc; Kassab, Ghassan S; Lochner, Donna R; McCulloch, Andrew D; Tran-Son-Tay, Roger; Trayanova, Natalia A

2016-09-01

Cardiovascular diseases (CVDs) are the leading cause of death in the western world. With the current development of clinical diagnostics to more accurately measure the extent and specifics of CVDs, a laudable goal is a better understanding of the structure-function relation in the cardiovascular system. Much of this fundamental understanding comes from the development and study of models that integrate biology, medicine, imaging, and biomechanics. Information from these models provides guidance for developing diagnostics, and implementation of these diagnostics to the clinical setting, in turn, provides data for refining the models. In this review, we introduce multi-scale and multi-physical models for understanding disease development, progression, and designing clinical interventions. We begin with multi-scale models of cardiac electrophysiology and mechanics for diagnosis, clinical decision support, personalized and precision medicine in cardiology with examples in arrhythmia and heart failure. We then introduce computational models of vasculature mechanics and associated mechanical forces for understanding vascular disease progression, designing clinical interventions, and elucidating mechanisms that underlie diverse vascular conditions. We conclude with a discussion of barriers that must be overcome to provide enhanced insights, predictions, and decisions in pre-clinical and clinical applications.

Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention

PubMed Central

Zhang, Yanhang; Barocas, Victor H.; Berceli, Scott A.; Clancy, Colleen E.; Eckmann, David M.; Garbey, Marc; Kassab, Ghassan S.; Lochner, Donna R.; McCulloch, Andrew D.; Tran-Son-Tay, Roger; Trayanova, Natalia A.

2016-01-01

Cardiovascular diseases (CVDs) are the leading cause of death in the western world. With the current development of clinical diagnostics to more accurately measure the extent and specifics of CVDs, a laudable goal is a better understanding of the structure-function relation in the cardiovascular system. Much of this fundamental understanding comes from the development and study of models that integrate biology, medicine, imaging, and biomechanics. Information from these models provides guidance for developing diagnostics, and implementation of these diagnostics to the clinical setting, in turn, provides data for refining the models. In this review, we introduce multi-scale and multi-physical models for understanding disease development, progression, and designing clinical interventions. We begin with multi-scale models of cardiac electrophysiology and mechanics for diagnosis, clinical decision support, personalized and precision medicine in cardiology with examples in arrhythmia and heart failure. We then introduce computational models of vasculature mechanics and associated mechanical forces for understanding vascular disease progression, designing clinical interventions, and elucidating mechanisms that underlie diverse vascular conditions. We conclude with a discussion of barriers that must be overcome to provide enhanced insights, predictions, and decisions in pre-clinical and clinical applications. PMID:27138523

A clinical study of patients with genetically confirmed Huntington's disease from India.

PubMed

Murgod, U A; Saleem, Q; Anand, A; Brahmachari, S K; Jain, S; Muthane, U B

2001-09-15

Clinical data across the globe especially in genetic diseases like Huntington's disease (HD) is most helpful when collected using standardized formats. This helps in proper comparison of clinical and genetic data. Herein, we report clinical data on 26 genetically confirmed HD patients from 19 Indian families predominantly from South India. Clinical data and evaluation was performed using standardized formats used by the Huntington Disease Study Group. Adult onset HD was commonest while Juvenile HD (onset <20 years) was observed in approximately 15% of patients. Chorea was the commonest presenting symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3, 11.5%). Impairment of saccades was observed in approximately 75% of patients. Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score but not the total behavioral score worsens with duration of symptoms. The functional checklist score correlates with total motor score rather than with duration of symptoms. We detail clinical characteristics in genetically confirmed HD patients from a predominantly South Indian cohort. We observed a slightly higher occurrence of Juvenile HD. Functional disabilities in our patients correlate with worsening of motor rather than behavioral symptoms.

Pseudologia Fantastica in the Emergency Department: A Case Report and Review of the Literature

PubMed Central

Teslyar, Polina; Friedman, Rohn

2017-01-01

Psychiatrists commonly encounter deception in the emergency department. This article presents the case of a patient who presents to the emergency department with an unusual and elaborate web of deceptions along multiple themes including feigning medical illness, multiple losses, and grandiose academic and athletic achievements. We review the clinical characteristics of pseudologia fantastica and discuss how this patient's constellation of malingering, factitious disorder, and personality disorder suggests this diagnosis. PMID:28573061

Chronic Liver Diseases in Children: Clinical Profile and Histology.

PubMed

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

PubMed Central

Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

2015-01-01

Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. PMID:26495305

Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer's disease.

PubMed

Xiong, Chengjie; van Belle, Gerald; Miller, J Philip; Morris, John C

2011-02-01

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally

Laterality of repetitive finger movement performance and clinical features of Parkinson's disease.

PubMed

Stegemöller, Elizabeth; Zaman, Andrew; MacKinnon, Colum D; Tillman, Mark D; Hass, Chris J; Okun, Michael S

2016-10-01

Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2Hz in persons with Parkinson's Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while "on" medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program.

PubMed

Held, Peter; Himmelmann, Anders; Ditmarsch, Marc

2016-07-01

Ticagrelor (P2Y12 receptor antagonist) is presently indicated for preventing atherothrombotic events in patients with acute coronary syndrome and patients with a history of myocardial infarction. The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular, indication-seeking outcome studies, aiming to evaluate ticagrelor across the spectrum of patients with atherothrombotic disease. Results of two large-scale trials support a benefit for ticagrelor in patients with acute coronary syndrome (PLATO; ClinicalTrials.gov: NCT00391872) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54; ClinicalTrials.gov: NCT01225562). Ongoing trials will provide information on the efficacy and safety of ticagrelor in patients with acute ischemic stroke or transient ischemic attack (SOCRATES; ClinicalTrials.gov: NCT01994720), peripheral artery disease (EUCLID; ClinicalTrials.gov: NCT01732822) and coronary artery disease in patients with Type 2 diabetes mellitus (THEMIS: ClinicalTrials.gov: NCT01991795).

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Patients

PubMed Central

2011-01-01

Executive Summary Objective The objective of this evidence-based analysis was to evaluate the clinical utility of serologic testing for celiac disease in asymptomatic individuals presenting with one of the non-gastrointestinal conditions evaluated in this report. The clinical utility was based on the effects of a gluten-free diet (GFD) on outcomes specific to each of these conditions. The prevalence of celiac disease in asymptomatic individuals and one of these non-gastrointestinal conditions was also evaluated. Clinical Need and Target Population Celiac Disease Celiac disease is an autoimmune disease characterized by a chronic inflammatory state of the proximal small bowel mucosa accompanied by structural and functional changes. Technology Under Evaluation Serologic Tests for Celiac Disease There are a number of serologic tests for celiac disease available. Serologic tests are automated with the exception of the anti-endomysial antibody test, which is more time-consuming and operator-dependent than the other tests. Research Questions What is the prevalence of asymptomatic celiac disease in patients presenting with one of the non-gastrointestinal conditions evaluated? What is the effect of the gluten-free diet on condition-specific outcomes in patients with asymptomatic celiac disease presenting with one of the non-gastrointestinal conditions evaluated? What is the clinical utility of serologic testing for celiac disease in asymptomatic patients presenting with one of the non-gastrointestinal conditions evaluated? The clinical utility was defined as the impact of the GFD on disease specific outcomes. What is the risk of all-cause mortality and lymphoma in individuals with asymptomatic celiac disease? What is the budget impact of serologic testing for celiac disease in asymptomatic subjects presenting with one of the non-gastrointestinal conditions evaluated? Research Methods Study Population The study population consisted of individuals with newly diagnosed celiac

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

PubMed

Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

2014-11-11

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

Trial design innovations: Clinical trials for treatment of neuropsychiatric symptoms in Alzheimer's Disease

PubMed Central

Zhong, K

2015-01-01

Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers. PMID:26206713

Rapid clinical diagnosis of Legionnaires' disease during the "herald wave" of the swine influenza (H1N1) pandemic: the Legionnaires' disease triad.

PubMed

Cunha, Burke A; Mickail, Nardeen; Syed, Uzma; Strollo, Stephanie; Laguerre, Marianne

2010-01-01

In adults hospitalized with atypical community-acquired pneumonia (CAP), Legionnaires' disease is not uncommon. Legionnaire's disease can be differentiated from typical CAPs and from other atypical CAPs based on its characteristic pattern of extrapulmonary organ involvement. The first clinically useful diagnostic weighted point score system for the clinical diagnosis of Legionnaires' disease was developed by the Infectious Disease Division at Winthrop-University Hospital in the 1980s. It has proven to be diagnostically accurate and useful for more than two decades, but was time-consuming. Because Legionella spp. diagnostic tests are time-dependent and problematic, a need was perceived for a rapid, simple way to render a clinical, syndromic diagnosis of Legionnaires' disease pending Legionella test results. During the "herald wave" of the swine influenza (H1N1) pandemic in the New York area, our hospital, like others, was inundated with patients who presented to the Emergency Department with influenza-like illnesses (ILIs) for H1N1 testing/evaluation. Most patients with ILIs did not have swine influenza. Hospitalized patients with ILIs who tested positive with rapid influenza diagnostic tests (RIDTs) were placed on influenza precautions and treated with oseltamivir. Unfortunately, approximately 30% of adult patients admitted with an ILI had negative RIDTs. Because the definitive laboratory diagnosis of H1N1 pneumonia by reverse transcription-polymerase chain reaction(RT-PCR), testing was restricted by health departments, resulted in clinical and infection control dilemmas in determining which RIDT-negative patients did, in fact, have H1N1 pneumonia. Accordingly, a diagnostic weighted point score system was developed for H1N1 pneumonia patients, based on RT-PCR positivity by the Infectious Disease Division at Winthrop-University Hospital. This diagnostic point score system for hospitalized adults with negative RIDTs was time-consuming. As the pandemic progressed, a

Evidence-based clinical practice guideline for adult Still's disease.

PubMed

Mimura, Toshihide; Kondo, Yuya; Ohta, Akihide; Iwamoto, Masahiro; Ota, Akiko; Okamoto, Nami; Kawaguchi, Yasushi; Kono, Hajime; Takasaki, Yoshinari; Takei, Shuji; Nishimoto, Norihiro; Fujimoto, Manabu; Asanuma, Yu Funakubo; Mimori, Akio; Okiyama, Naoko; Kaneko, Shunta; Takahashi, Hiroyuki; Yokosawa, Masahiro; Sumida, Takayuki

2018-05-09

Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release. Because we wanted to construct CPG for ASD to encompass both adult-onset Still's disease (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we also included SR data from sJIA in this study. Twenty-six CQs were selected and roughly divided into the following items: (1) clinical findings (CQs 1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4) treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the strength of the recommendations for these CQs were decided by a modified Delphi method. We have developed the first published CPG for ASD including AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will help rheumatologists, non-specialized physicians, other healthcare providers, medical and health-related students, and patients and their family members to understand and treat ASD.

CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

PubMed

Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

2014-05-01

There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF

How disease advocacy organizations participate in clinical research: a survey of genetic organizations.

PubMed

Landy, David C; Brinich, Margaret A; Colten, Mary Ellen; Horn, Elizabeth J; Terry, Sharon F; Sharp, Richard R

2012-02-01

Disease advocacy organizations may assist in the conduct of research in a variety of ways. We sought to characterize how disease advocacy organizations participate in clinical research and perceive their contributions. Postal and electronic surveys administered to leaders of disease advocacy organizations for genetic conditions identified through the Genetic Alliance's Disease InfoSearch. Of the 201 disease advocacy organizations approached, 124 (62%) responded. In the past 2 years, 91% of these organizations had assisted in participant recruitment, 75% collected data, 60% provided a researcher with financial support, and 56% assisted with study design. Forty-five percent of these organizations also supported a research registry or biobank. Few disease advocacy organization leaders (12%) reported regrets about research studies they had supported. Most (68%) felt their involvement in clinical research had increased the amount of research on their condition and that researchers should consult organizations like theirs in deciding how to recruit participants (58%) and in selecting research topics (56%). In addition to providing financial support, disease advocacy organizations participate directly in multiple aspects of research, ranging from study design and patient recruitment to data collection and analysis. Leaders of these organizations feel strongly that scientists and research sponsors should engage them as partners in the conduct of clinical research.

Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

PubMed Central

Sahasrabhojane, Pranoti; Saldana, Miguel; Yao, Hui; Su, Xiaoping; Horstmann, Nicola; Thompson, Erika; Flores, Anthony R.

2014-01-01

The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen. PMID:24750901

Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

PubMed Central

Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

2014-01-01

Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

The effect of disease risk probability and disease type on interest in clinic-based versus direct-to-consumer genetic testing services.

PubMed

Sherman, Kerry; Shaw, Laura-Kate; Champion, Katrina; Caldeira, Fernanda; McCaskill, Margaret

2015-10-01

The effect of disease-specific cognitions on interest in clinic-based and direct-to-consumer (DTC) genetic testing was assessed. Participants (N = 309) responded to an online hypothetical scenario and received genetic testing-related messages that varied by risk probability (25, 50, 75 %) and disease type (Alzheimer's disease vs. Type 2 Diabetes). Post-manipulation interest increased for both testing types, but was greater for clinic-based testing. Interest was greater for Type 2 Diabetes than for Alzheimer's disease, the latter perceived as more severe and likely, and less treatable and preventable. For DTC testing only, participants allocated to the high risk condition (75 %) had greater testing interest than those in the low (25 %) category. DTC testing is perceived as a viable, but less preferred, option compared with clinic-based testing. Particularly when considering DTC genetic testing, there is a need to emphasize subjective disease-related perceptions, including risk probability.

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.

PubMed

Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

2014-09-01

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

PubMed Central

Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

2014-01-01

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions – the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1–13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols. PMID:25077519

Cardiovascular Disease in Women: Clinical Perspectives

PubMed Central

Garcia, Mariana; Mulvagh, Sharon L.; Merz, C. Noel Bairey; Buring, Julie E.; Manson, JoAnn E.

2016-01-01

Cardiovascular disease (CVD) continues to be the leading cause of death among women in the United States, accounting for approximately one of every three female deaths. Sex-specific data focused on CVD has been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex-differences as they relate to clinical practice in the prevention, diagnosis, and treatment of CVD. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including: myocardial infarction associated with non-obstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other CVD entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease and abdominal aortic aneurysms, are also briefly reviewed. Lastly, recommendations for cardiac rehabilitation are addressed. PMID:27081110

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse.

PubMed

Garcelon, Nicolas; Neuraz, Antoine; Salomon, Rémi; Bahi-Buisson, Nadia; Amiel, Jeanne; Picard, Capucine; Mahlaoui, Nizar; Benoit, Vincent; Burgun, Anita; Rance, Bastien

2018-05-31

Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Children's Hospital contains data collected during normal care for thousands of patients. Dr. Warehouse is oriented toward the exploration of clinical narratives. In this study, we present our method to find phenotypes associated with diseases of interest. We leveraged the frequency and TF-IDF to explore the association between clinical phenotypes and rare diseases. We applied our method in six use cases: phenotypes associated with the Rett, Lowe, Silver Russell, Bardet-Biedl syndromes, DOCK8 deficiency and Activated PI3-kinase Delta Syndrome (APDS). We asked domain experts to evaluate the relevance of the top-50 (for frequency and TF-IDF) phenotypes identified by Dr. Warehouse and computed the average precision and mean average precision. Experts concluded that between 16 and 39 phenotypes could be considered as relevant in the top-50 phenotypes ranked by descending frequency discovered by Dr. Warehouse (resp. between 11 and 41 for TF-IDF). Average precision ranges from 0.55 to 0.91 for frequency and 0.52 to 0.95 for TF-IDF. Mean average precision was 0.79. Our study suggests that phenotypes identified in clinical narratives stored in Electronic Health Record can provide rare disease specialists with candidate phenotypes that can be used in addition to the literature. Clinical Data Warehouses can be used to perform Next Generation Phenotyping, especially in the context of rare diseases. We have developed a method to detect phenotypes associated with a group of patients using medical concepts extracted from free-text clinical narratives.

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

PubMed

Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Targeted therapies for Parkinson's disease: From genetics to the clinic.

PubMed

Sardi, S Pablo; Cedarbaum, Jesse M; Brundin, Patrik

2018-04-27

The greatest unmet medical need in Parkinson's disease (PD) is treatments that slow the relentless progression of symptoms. The discovery of genetic variants causing and/or increasing the risk for PD has provided the field with a new arsenal of potential therapies ready to be tested in clinical trials. We highlight 3 of the genetic discoveries (α-synuclein, glucocerebrosidase, and leucine-rich repeat kinase) that have prompted new therapeutic approaches now entering the clinical stages. We are at an exciting juncture in the journey to developing disease-modifying treatments based on knowledge of PD genetics and pathology. This review focuses on therapeutic paradigms that are under clinical development and highlights a wide range of key outstanding questions in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

PubMed

Buliman, A; Tataranu, L G; Paun, D L; Mirica, A; Dumitrache, C

2016-01-01

Cushing's disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing's disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing's disease using the most recent available guidelines.

Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

PubMed

Kieburtz, Karl; Tilley, Barbara C; Elm, Jordan J; Babcock, Debra; Hauser, Robert; Ross, G Webster; Augustine, Alicia H; Augustine, Erika U; Aminoff, Michael J; Bodis-Wollner, Ivan G; Boyd, James; Cambi, Franca; Chou, Kelvin; Christine, Chadwick W; Cines, Michelle; Dahodwala, Nabila; Derwent, Lorelei; Dewey, Richard B; Hawthorne, Katherine; Houghton, David J; Kamp, Cornelia; Leehey, Maureen; Lew, Mark F; Liang, Grace S Lin; Luo, Sheng T; Mari, Zoltan; Morgan, John C; Parashos, Sotirios; Pérez, Adriana; Petrovitch, Helen; Rajan, Suja; Reichwein, Sue; Roth, Jessie Tatsuno; Schneider, Jay S; Shannon, Kathleen M; Simon, David K; Simuni, Tanya; Singer, Carlos; Sudarsky, Lewis; Tanner, Caroline M; Umeh, Chizoba C; Williams, Karen; Wills, Anne-Marie

2015-02-10

There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?

PubMed Central

Mendoza, Fabian A.; Keyes-Elstein, Lynette L.; Jimenez, Sergio A.

2012-01-01

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should be of at least 12 months. Sample size calculations should consider differences that exceed the Minimal Important Difference. Other relevant trial designs and potential threats to study validity are also discussed. Previous SSc-disease modifying trials have been beset by high dropout rates. Analyses on the subset of subjects completing the trial or applying the last-observation-carried-forward approach can potentially lead to biased estimates and false conclusions. Strategies for retention of subjects should be included at the design stage and analyses to account for missing data should be performed. PMID:22422541

Semantic Memory in the Clinical Progression of Alzheimer Disease.

PubMed

Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Natural history and clinical detection of undiagnosed coeliac disease in a North American community.

PubMed

Hujoel, I A; Van Dyke, C T; Brantner, T; Larson, J; King, K S; Sharma, A; Murray, J A; Rubio-Tapia, A

2018-05-01

Coeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding. To determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease. This was a case-control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age- and gender-matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing. Of 47 557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight-matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2 years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85-1.63, P = 0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P = 0.001). This study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed. © 2018 John Wiley & Sons Ltd and Mayo Foundation.

The Disease Burden and Clinical Characteristics of Inflammatory Bowel Disease in the Chinese Population: A Systematic Review and Meta-Analysis.

PubMed

Li, Xue; Song, Peige; Li, Jun; Tao, Yuchang; Li, Guowei; Li, Xiumin; Yu, Zengli

2017-02-28

The temporal trend of inflammatory bowel disease (IBD) incidence is reported to be increasing in worldwide regions; however, reports focusing on China are sparse. The aim of this study was to provide an overview of the disease burden and clinical features of IBD in the Chinese population. We searched Medline, EMBASE, and another two Chinese databases. A parallel literature review and data extraction were conducted. Meta-analysis was performed to estimate the summary incidence rate of Crohn's disease (CD) and ulcerative colitis (UC). The constituent ratios with 95% CI were calculated for clinical phenotypes and classifications. The literature review included 47 publications. The summary incidence rate of IBD was 1.74 (95% CI: 1.08; 2.40) per 100,000 person years, and the corresponding incidence rates of CD and UC were 0.40 (95% CI: 0.23; 0.57) and 1.18 (95% CI: 0.81; 1.56) per 100,000 person years, respectively. The sex distribution analysis indicated a male predominance in both CD (sex ratio: 1.64; 95% CI: 1.47-1.84) and UC (sex ratio: 1.29; 95% CI: 1.21-1.38). The clinical characteristics were summarized using data from 2283 CD cases and 17,958 UC cases; in which the majority of CD patients were diagnosed between 17-40 years of age, with non-stricturing and non-penetrating disease, varied disease locations, and less extra-intestinal manifestation. UC cases were featured with later disease diagnosis, a more severe disease course, more segmental lesions, and less extra-intestinal manifestations. Our study provided an estimated disease burden of IBD and demonstrated distinct clinical features in the Chinese population. Large-scale population-based studies are needed to further evaluate these findings.

Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

PubMed

DeWard, Stephanie J; Wilson, Ashley; Bausell, Heather; Volz, Ashley S; Mooney, Kimberly

2014-02-01

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.

Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.

PubMed

King, Jill; Pana, Zoi-Dorothea; Lehrnbecher, Thomas; Steinbach, William J; Warris, Adilia

2017-09-01

Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.

Clinical Application Of Advanced Infrared Thermography (IRT) In Locomotor Diseases

NASA Astrophysics Data System (ADS)

Engel, Joachim-Michael

1983-11-01

Locomotor diseases is a wide range of about 450 different illnesses with all different pathologies, clinical and prognostic features and response to treatment. No single method will be able to cover the whole spectrum of local and systemic signs and symptoms. Nevertheless there is a need for objective measurements at the site of disease: clinical examination is often enough depending from subjective estimations and personal experiance of the clinician. Laboratory tests only show the systemic effect of the disease, like inflammation. X-rays are restricted to the detection of structural changes appearing late during the pathological process, even when using different techniques. Here IRT offers several advantages to the clinician as well as to the patient. As a non invasive method it monitors the course of disease at the anatomic site of pathology. Quantitative figures calculated from the thermogram,either taken at steady-state or during dynamic tests, are essential for differential diagnosis and follow-up. Advanced IRT camera systems fulfill all requirements set up for medical thermography recently by the National Bureau of Standards. Although, the user should check his system daily with regard to precision of absolute temperature measurements. Standardisation of recording technique is essential as well,to get reliable results. Ambient conditions must be adapted to the locomotor disease pathology under study. Advanced IRT systems , e.g. ZEISS-IKOTHERM, together with image processing capability and special software, e.g. THERMOTOM package, are valuable tools to the rheumatologist for diagnosing and monitoring locomotor diseases.

Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates.

PubMed

de Albuquerque Seixas, Emerson; Carmello, Beatriz Leone; Kojima, Christiane Akemi; Contti, Mariana Moraes; Modeli de Andrade, Luiz Gustavo; Maiello, José Roberto; Almeida, Fernando Antonio; Martin, Luis Cuadrado

2015-05-01

Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in São Paulo state were analyzed for associations between significant coronary artery diseases (≥70% stenosis in one or more epicardial coronary arteries or ≥50% in the left main coronary artery) and clinical parameters. Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.

Funding agencies and disease organizations: resources and recommendations to facilitate ALS clinical research.

PubMed

Chad, David A; Bidichandani, Sanjay; Bruijn, Lucie; Capra, J Donald; Dickie, Brian; Ferguson, John; Figlewicz, Denise; Forsythe, Melissa; Kaufmann, Petra; Kirshner, Annette; Monti, William

2013-05-01

Ten groups presented their perspectives on facilitating clinical research in ALS including four federal agencies, four disease organizations, one foundation and one advocacy group. The federal agencies (National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Office of Rare Diseases Research, Department of Defense) encourage fostering a team approach between pre-clinical and clinical research investigators, coordinating with patient groups in the early phases of clinical studies, enhancing private and public partnerships, and investigating the interplay between genetic susceptibility and environmental exposure. The disease organizations (Muscular Dystrophy Association, ALS Association, ALS Society of Canada, and the Motor Neurone Disease Association UK) support fellowship training programs to develop ALS clinician scientists, and encourage work on the epidemiology of ALS, on genetic and epigenetic mechanisms that are relevant to ALS pathogenesis, on developing ALS registries and biobanks, and building bridges of collaboration among study groups. The Foundation supports innovative projects, including stem-cell research, and Patient Advocacy is committed to supporting excellence in ALS research and patient care, and believes strongly in enhancing communication between patients and members of the research community.

Clinical Features and Extraintestinal Manifestations of Crohn Disease in Children

PubMed Central

Lee, Young Ah; Chun, Peter; Hwang, Eun Ha; Mun, Sang Wook; Lee, Yeoun Joo

2016-01-01

Purpose The aim of this study was to investigate the clinical features and extraintestinal manifestations (EIMs) of Crohn disease (CD) in Korean pediatric patients. Methods The medical records of 73 children diagnosed with CD were retrospectively reviewed. Data regarding baseline demographic and clinical characteristics, including CD phenotype at diagnosis based on the Montreal classification, and clinical features and course of EIMs were investigated. Results Fifty-two (71.2%) of the patients were males. The mean age of the patients was 12.5 years. The mean follow-up period was 3.4 years. The disease location was ileal in 3 (4.1%) of the patients, colonic in 13 (17.8%), ileocolonic in 56 (76.7%). The clinical behavior was inflammatory in 62 (84.9%) of the patients, stricturing in 8 (11.0%), and penetrating in 3 (4.1%). Perianal abscesses or fistulas were found in 37 (50.7%) of the patients. EIMs observed during the study period were anal skin tag in 25 patients (34.2%), hypertransaminasemia in 20 (27.4%), peripheral arthritis in 2 (2.7%), erythema nodosum in 2 (2.7%), vulvitis in 1 (1.4%), uveitis in 1 (1.4%), and pulmonary thromboembolism in 1 (1.4%). Conclusion Perianal diseases and manifestations were present in more than half of Korean pediatric CD patients at diagnosis. Inspection of the anus should be mandatory in Korean children with suspicious CD, as perianal fistulas, abscesses, and anal skin tags may be the first clue to the diagnosis of CD. PMID:28090468

The role of tau in the pathological process and clinical expression of Huntington’s disease

PubMed Central

Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan; Cisbani, Giulia; Drouin-Ouellet, Janelle; Spillantini, Maria G.; Cicchetti, Francesca

2015-01-01

Huntington’s disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington’s disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington’s disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington’s disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington’s disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype–phenotype analysis of a large cohort of patients with Huntington’s disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington’s disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington’s disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington’s disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT

Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow.

PubMed

López-Campos, Jose Luis; Abad Arranz, María; Calero Acuña, Carmen; Romero Valero, Fernando; Ayerbe García, Ruth; Hidalgo Molina, Antonio; Aguilar Pérez-Grovas, Ricardo Ismael; García Gil, Francisco; Casas Maldonado, Francisco; Caballero Ballesteros, Laura; Sánchez Palop, María; Pérez-Tejero, Dolores; Segado, Alejandro; Calvo Bonachera, Jose; Hernández Sierra, Bárbara; Doménech, Adolfo; Arroyo Varela, Macarena; González Vargas, Francisco; Cruz Rueda, Juan Jose

2015-01-01

Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow. A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints. This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.

An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting.

PubMed

Hack, Nawaz; Fayad, Sarah M; Monari, Erin H; Akbar, Umer; Hardwick, Angela; Rodriguez, Ramon L; Malaty, Irene A; Romrell, Janet; Shukla, Aparna A Wagle; McFarland, Nikolaus; Ward, Herbert E; Okun, Michael S

2014-01-01

To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

Metastatic Crohn disease clinically reminiscent of erythema nodosum on the right leg.

PubMed

Park, Hyun C; Kim, Hyun W; Park, Chan G; Ko, Joo Y

2016-09-01

Cutaneous manifestations are well-recognized complications of Crohn disease (CD) that can be divided into disease-specific and reactive conditions. One of the most common reactive conditions is erythema nodosum (EN), which presents as subcutaneous tender nodules most often on the legs. On the other hand, metastatic Crohn disease (MCD) is a rare cutaneous manifestation of CD defined as the presence of noncaseating granulomas that are not contiguous with the gastrointestinal (GI) tract. The clinical presentation of MCD is variable; however, lesions often are located on the legs and genital region. We report the case of a 21-year-old woman with a 6-year history of CD who presented with MCD clinically simulating EN.

Parkinson's disease--the debate on the clinical phenomenology, aetiology, pathology and pathogenesis.

PubMed

Jenner, Peter; Morris, Huw R; Robbins, Trevor W; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V; Brooks, David

2013-01-01

The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article--widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include--Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).

Advanced clinical insights & practice: ischemic heart disease.

PubMed

Benner, Randall W; Zavarella, Matthew S

2008-03-01

This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue.

Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options.

PubMed

Tanna, Preena; Strauss, Rupert W; Fujinami, Kaoru; Michaelides, Michel

2017-01-01

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4 Significant advances have been made over the last 10 years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and genotypic characteristics of the disease, conventional and novel imaging findings, current knowledge of animal models and pathogenesis, and the multiple avenues of intervention being explored. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical Practice in Inflammatory Bowel Diseases: A Systematic Review.

PubMed

de Jong, Marin J; Huibregtse, Roxanne; Masclee, Ad A M; Jonkers, Daisy M A E; Pierik, Marie J

2018-05-01

Mucosal inflammation must be carefully monitored to improve the long-term outcomes of patients with inflammatory bowel diseases (IBD). Patient-reported outcome measures (PROMs) are used increasingly to monitor disease activity in clinical practice and as endpoints in clinical trials. We performed a systematic review to provide an overview of the available PROMs on IBD activity and to evaluate their diagnostic value. A systematic search of the PubMed, Medline, Cochrane library, and Embase databases using defined keywords, identified 973 articles. These were screened by 2 independent reviewers, and 37 articles on development or validation of PROMs to assess IBD activity were identified for further analysis. Based on the recommendations of the Food and Drug Administration (FDA), the following measurement properties were evaluated: content, construct, and criterion validity; reliability; and responsiveness to change. In addition, data on ease of use in clinical practice were collected. Seventeen articles presenting 20 different PROMs were included the final analysis, although none met all the FDA-recommended criteria. Only 2 PROMs (patient-reported Harvey Bradshaw Index and Simple Clinical Colitis Activity Index scores) reported patient involvement during its development. Only 6 PROMs (patient-reported global assessment, patient assessment of disease activity, mobile health index for Crohn's disease, mobile health index for ulcerative colitis, patient-reported outcome derived from the Mayo score, and the 6-point Mayo score) were validated as markers of IBD activity, using findings from endoscopy as the reference standard; these PROMs identified patients with mucosal inflammation with area under the curve values of 0.63-0.82. The mobile health index for CD and UC scores had the best measurement properties for use in clinical practice and in clinical trials. In a systematic review, we identified more than 20 PROMS that have been developed and tested for their ability to

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer’s disease

PubMed Central

Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian

2017-01-01

Abstract Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer’s disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer’s disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer’s disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks—the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer’s disease patients with and without cerebrovascular disease. Alzheimer’s disease patients without cerebrovascular disease, but not Alzheimer’s disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer’s disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer’s disease patients with and without cerebrovascular disease. Across Alzheimer’s disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer’s disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer’s disease patients with cerebrovascular disease showed increased executive control network structural

Diffuse Lewy body disease: clinical features in 15 cases.

PubMed Central

Byrne, E J; Lennox, G; Lowe, J; Godwin-Austen, R B

1989-01-01

Fifteen cases of diffuse Lewy body disease were diagnosed on pathological grounds during a single year in one health district. The range and frequency of clinical features contrast strikingly with previous reports. The majority of cases presented with classical levodopa-responsive Parkinson's disease either alone (6 cases) or with mild cognitive impairment (3 cases); the remaining 6 cases presented with cognitive impairment alone. In time almost all patients developed both dementia and Parkinsonism. The dementia was cortical in type, but unusual in that most (12 cases) showed day-to-day fluctuation in severity at some point in their illness. These findings suggest that diffuse Lewy body disease is not rare, and that it presents in a range of ways from dementia with subsequent Parkinsonism to Parkinson's disease with subsequent dementia. The latter mode of presentation suggests that it should be considered as a significant pathological substrate of dementia in Parkinson's disease. Images PMID:2545827

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

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

Sibille, A.; Eng, C.M.; Kim, S.J.

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, andmore » severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.« less

Clinical signs and concurrent diseases of hypothyroidism in dogs and cats.

PubMed

Scott-Moncrieff, J Catharine

2007-07-01

Canine hypothyroidism may present with a wide range of clinical signs. The most common clinical signs are those of a decreased metabolic rate and dermatologic manifestations; however, many other clinical signs have been associated with hypothyroidism. There is strong evidence for a causal relation between hypothyroidism and a variety of neurologic abnormalities; however, the association between hypothyroidism and other manifestations, such as reproductive dysfunction, clinical heart disease, and behavioral abnormalities, is less compelling. Further studies are necessary to determine the full spectrum of disorders caused by hypothyroidism.

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical

Celiac disease in Saudi children. Evaluation of clinical features and diagnosis.

PubMed

Saeed, Anjum; Assiri, Asaad; Assiri, Hebah; Ullah, Anhar; Rashid, Mohsin

2017-09-01

 Objectives: To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease. Methods: All children (less than 18 years) with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh,  Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading. Results: A total of 59 children had confirmed celiac disease. Thirty (50.8%) were male. Median age was 8 years (range 1 to 16 years). The mean duration of symptoms before diagnosis was 2.3 (±1.5) years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease. Conclusion: Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

Clinical and geographic patterns of rheumatic heart disease in outpatients attending cardiology clinic in western Kenya.

PubMed

Lumsden, Rebecca H; Akwanalo, Constantine; Chepkwony, Stella; Kithei, Anne; Omollo, Vincent; Holland, Thomas L; Bloomfield, Gerald S; O'Meara, Wendy P

2016-11-15

Rheumatic heart disease (RHD) remains a leading cause of cardiovascular mortality in sub-Saharan Africa. Identifying high risk populations and geographic patterns of disease is crucial to developing RHD prevention and screening strategies in endemic areas. To identify clinical and geographical trends in RHD throughout western Kenya METHODS: We conducted a retrospective chart review of all patients <50years old attending adult cardiology clinic at a national referral hospital in western Kenya. Demographic information, residential location and cardiac history were collected. We mapped the spatial distribution of cardiac disease rates and analyzed the effect of distance from the hospital on RHD status. Two-thirds (64%) of cardiology clinic patients <50years old (n=906) had RHD. RHD patients were younger (26 vs. 33years, p<0.001) and more often female (69% vs. 59%, p=0.001) than non-RHD patients. Global clustering of disease rates existed within 200km of the hospital with significant clustering of the RHD and non-RHD rate difference surrounding the hospital (Moran's I: 0.3, p=0.001). There was an interaction between ethnicity and distance from the hospital such that the odds of RHD decreased with further distance for Nilotes, but the odds of RHD increased with further distance for non-Nilotes CONCLUSION: Most adult cardiology patients treated at a national referral hospital in western Kenya have RHD. Young people and females are commonly affected. Ethnicity and distance to the hospital interdependently affect the odds of RHD. Future studies in this area should consider the impact of ethnic predisposition to RHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Understanding complex clinical reasoning in infectious diseases for improving clinical decision support design.

PubMed

Islam, Roosan; Weir, Charlene R; Jones, Makoto; Del Fiol, Guilherme; Samore, Matthew H

2015-11-30

Clinical experts' cognitive mechanisms for managing complexity have implications for the design of future innovative healthcare systems. The purpose of the study is to examine the constituents of decision complexity and explore the cognitive strategies clinicians use to control and adapt to their information environment. We used Cognitive Task Analysis (CTA) methods to interview 10 Infectious Disease (ID) experts at the University of Utah and Salt Lake City Veterans Administration Medical Center. Participants were asked to recall a complex, critical and vivid antibiotic-prescribing incident using the Critical Decision Method (CDM), a type of Cognitive Task Analysis (CTA). Using the four iterations of the Critical Decision Method, questions were posed to fully explore the incident, focusing in depth on the clinical components underlying the complexity. Probes were included to assess cognitive and decision strategies used by participants. The following three themes emerged as the constituents of decision complexity experienced by the Infectious Diseases experts: 1) the overall clinical picture does not match the pattern, 2) a lack of comprehension of the situation and 3) dealing with social and emotional pressures such as fear and anxiety. All these factors contribute to decision complexity. These factors almost always occurred together, creating unexpected events and uncertainty in clinical reasoning. Five themes emerged in the analyses of how experts deal with the complexity. Expert clinicians frequently used 1) watchful waiting instead of over- prescribing antibiotics, engaged in 2) theory of mind to project and simulate other practitioners' perspectives, reduced very complex cases into simple 3) heuristics, employed 4) anticipatory thinking to plan and re-plan events and consulted with peers to share knowledge, solicit opinions and 5) seek help on patient cases. The cognitive strategies to deal with decision complexity found in this study have important

Clinical lipidomics: a new way to diagnose human diseases.

PubMed

Lv, Jiapei; Zhang, Linlin; Yan, Furong; Wang, Xiangdong

2018-04-27

Lipidomics is a measurement of a large scale of lipid species to understand roles of their carbon atoms, dual bonds, or isomerism in the lipid molecule. Clinical lipidomics was recently defined "as a new integrative biomedicine to discover the correlation and regulation between a large scale of lipid elements measured and analyzed in liquid biopsies from patients with those patient phenomes and clinical phenotypes". The first step to translate lipidomics into clinical lipidomics is to settle a number of standard operation procedures and protocols of lipidomics performance and measurement. Clinical lipidomics is the part of clinical trans-omics which was coined as a new emerging scientific discipline where clinical phenomes are integrated with molecular multiomics. We believe it is the time to translate lipid science and lipidomics into clinical application and to understand the importance of clinical lipidomics as one of the most helpful approaches during the design and decision-making of therapeutic strategies for individuals. We emphasize here that clinical lipidomics should be merged with clinical phenomes, e.g. patient signs and symptoms, biomedical analyses, pathology, images, and responses to therapies, although it is difficult to integrate and fuse the information of clinical lipidomics with clinical phenomes. It will be a great achievement if we can draw the networks of lipidomic species fused with networks of genes and proteins to describe the molecular mechanisms of the disease in multi-dimensions.

Clinical and radiological features of Marchiafava–Bignami disease

PubMed Central

Dong, Xiaoyu; Bai, Chaobo; Nao, Jianfei

2018-01-01

Abstract Marchiafava–Bignami disease (MBD) is a rare neurological disease usually associated with chronic alcoholism and characterized by demyelination and necrosis. Our aims were to describe the clinicoradiological features and identify factors that may affect the prognosis of patients with MBD. We examined clinical manifestations, laboratory results, and neuroradiological features of 9 patients with MBD. The patients were classified into 2 subgroups (favorable and poor outcome subgroups) based on the Modified Oxford Handicap Scale (MOSH). In addition, we compared the clinical and neuroimaging features between the 2 subgroups. Nine adult male patients (age of onset range 37–62 years, with a mean age of 47.00 ± 14.50 years) were included in this study. According to MOSH, 4 patients were placed in the poor outcome subgroup (MOHS ≥ 3), 5 patients were placed in the favorable outcome subgroup (MOHS ≤ 2). Relatively high score of MAST-C (≥6) (P = .008), extracallosal lesions (P = .048), GCS (P = .026), cerebral lobe impairment (P = .048) was significantly more common in the poor outcome subgroup. Clinical manifestations of MBD are variable and lack specificity. Early diagnosis by relatively specific performance of bisymmetric lesions in corpus callosum of diffusion-weighted imaging (DWI) may affect the prognosis. The prognosis of patients with severe disturbance of consciousness, heavy alcohol consumption, extracallosal lesions, cerebral lobe impairment is probably unfavorable. PMID:29384842

Alzheimer disease in women: a clinical and genetics perspective.

PubMed

Gies, Cheryl; Lessick, Mira

2009-08-01

Upon completion of this activity, the learner will be able to: 1. Identify clinical and genetic characteristics and considerations associated with Alzheimer disease (AD). 2. Describe assessment and management strategies for AD. 3. Describe nursing implications for women and families with, or at risk for, AD.

Clinical Outcome Assessments: Use of Normative Data in a Pediatric Rare Disease.

PubMed

Phillips, Dawn; Leiro, Beth

2018-05-01

Pediatric rare diseases present unique challenges in clinical trial design and in selection of clinical outcome assessments (COAs) used to support claims in medical product labeling. COAs that discriminate level of function relative to a normative sample are particularly important in the pediatric rare disease setting because the literature is often void of natural history data. Pediatric rare disease clinical trials will often include a wide age distribution. Gross and fine motor skills, communication, cognition, and independence in activities of daily living vary by age, and it may be difficult to distinguish between treatment effect and change due to developmental maturation. Asfotase alfa was granted breakthrough therapy designation and subsequently approved for the treatment of hypophosphatasia (HPP; a genetic metabolic musculoskeletal disorder) and is used in this discussion to illustrate COA selection in a pediatric rare disease. Multiple COAs with normative data in HPP clinical trials for asfotase alfa are presented. The assessment instruments included the Bayley Scales of Infant and Toddler Development-Third Edition, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, the Childhood Health Assessment Questionnaire, the Pediatric Outcomes Data Collection Instrument, handheld dynamometry, the 6-minute walk test, and the Modified Performance-Oriented Mobility Assessment-Gait scale. Multiple end points were required to adequately capture the impact of asfotase alfa treatment on the multiple systems affected in HPP. These data illustrate the importance of using multiple COAs that provide normative data and to use COAs early in the drug development process for rare pediatric disease. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

PubMed Central

Tarawneh, Rawan; Holtzman, David M.

2012-01-01

Alzheimer disease (AD) is the most common cause of dementia in the elderly. Clinicopathological studies support the presence of a long preclinical phase of the disease, with the initial deposition of AD pathology estimated to begin approximately 10–15 years prior to the onset of clinical symptoms. The hallmark clinical phenotype of AD is a gradual and progressive decline in two or more cognitive domains, most commonly involving episodic memory and executive functions, that is sufficient to cause social or occupational impairment. Current diagnostic criteria can accurately identify AD in the majority of cases. As disease-modifying therapies are being developed, there is growing interest in the identification of individuals in the earliest symptomatic, as well as presymptomatic, stages of disease, because it is in this population that such therapies may have the greatest chance of success. The use of informant-based methods to establish cognitive and functional decline of an individual from previously attained levels of performance best allows for the identification of individuals in the very mildest stages of cognitive impairment. PMID:22553492

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: DIAGNOSIS OF RECURRENCE IN CUSHING DISEASE.

PubMed

Fleseriu, Maria; Hamrahian, Amir H; Hoffman, Andrew R; Kelly, Daniel F; Katznelson, Laurence

2016-12-01

Recurrence of hypercortisolemia after initial treatment of Cushing disease (CD) is more common than previously thought, with a third of patients suffering a recurrence over their lifetime. Awareness of this high rate and delayed timeline (sometimes decades) of potential recurrence is critical and patients with CD should be monitored at regular intervals throughout their lives. In this manuscript, we review the complex evaluation needed for defining CD remission versus persistent disease after surgery, and focus on challenges in diagnosing early recurrent hypercortisolemia. Late night salivary cortisol appears to be an earlier predictor of recurrence when compared with urinary free cortisol (UFC) excretion. We also review the criteria suggested to define recurrence of hypercortisolemia in patients treated with medical therapy. Further research is needed to determine the optimal way to evaluate a patient with CD recurrence as well as the riskbenefit ratio of treatment in early, mild recurrent disease. ACTH = adrenocorticotropic hormone AI = adrenal insufficiency CD = Cushing disease CDDT = coupled dexamethasone desmopressin test CR = circadian rhythm CRH = corticotropin-releasing hormone GC = glucocorticoid GCR = global clinical response HPA = hypothalamic-pituitary-adrenal LDDST = low-dose dexamethasone suppression test LNSC = late-night salivary cortisol ODST = overnight dexamethasone suppression test TSS = trans-sphenoidal surgery.

Patterns of clinical presentation of adult coeliac disease in a rural setting.

PubMed

Jones, Sián; D'Souza, Charles; Haboubi, Nadim Y

2006-09-14

In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority of adult coeliac disease patients present with classical mal

Clinical characteristics and treatment outcomes of pulmonary disease caused by Mycobacterium chimaera.

PubMed

Moon, Seong Mi; Kim, Su-Young; Jhun, Byung Woo; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Shin, Sung Jae; Koh, Won-Jung

2016-12-01

Mycobacterium chimaera is a recently described species distinct from M. intracellulare. M. chimaera is regarded as less virulent than M. intracellulare. Using multi-locus sequence-based identification, M. chimaera lung disease was diagnosed in 11 patients. Clinical characteristics and outcomes of M. chimaera lung disease were comparable to M. intracellulare lung disease. Copyright © 2016 Elsevier Inc. All rights reserved.

HIV-associated salivary gland disease--clinical or imaging diagnosis?

PubMed

da Silva Rath, Inês Beatriz; Beltrame, Ana Paula C A; Carvalho, Aroldo P; Schaeffer, Marcela B; Almeida, Izabel C S

2015-07-01

This work aimed at studying the salivary gland disease (SGD) as it relates to associated factors, such as persistent generalised lymphadenopathy (PGL), lymphocytic interstitial pneumonia (LIP), clinical and immunological features of AIDS, and salivary flow rate and pH, as well as at exploring the relationship between the clinical diagnosis and the imaging diagnosis by ultrasound (US) examination of the parotid glands. Information regarding the observation of parotid gland enlargement, PGL, LIP, and clinical and immunological features of AIDS was gathered from medical records, and a saliva sample for unstimulated salivary flow rate and pH measurement was collected from 142 children aged 3 through 10 years treated at the Department of Infectious Diseases of Joana de Gusmão Children's Hospital, Florianópolis, SC, Brazil. High-resolution ultrasonography was performed in 58 children. Pearson's chi-square test and t-test were used to evaluate the association between the variables. A significant association was found between SGD and LIP. Ultrasound revealed a 50% higher incidence of SGD that was not reported in the patients' records. US examination proved to be essential for the correct diagnosis and monitoring of the progression of HIV/SGD. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Connecting Gaucher and Parkinson Disease: Considerations for Clinical and Research Genetic Counseling Settings.

PubMed

Cook, Lola; Schulze, Jeanine

2017-12-01

There are multiple autosomal recessive disorders in which carriers may be at risk for other diseases. This observation calls into question the previous understanding that carriers of autosomal recessive disorders escape clinical consequences. We also know that childhood genetic conditions may have adult disease counterparts (Zimran et al., The Israel Medical Association Journal: IMAJ, 16(11), 723-724, 2014). Individuals who have Gaucher disease and carriers of the disorder are at increased risk for a seemingly unrelated and complex neurological condition, Parkinson disease. Parkinson disease is, in part, caused by the same mutations in the GBA gene that lead to Gaucher disease, and the two conditions are thought to have shared pathophysiology. Briefly reviewed are how these two diseases historically became linked, where their paths cross, potential problems and considerations in disclosure of the link, and current guidelines and research in this area. Genetic counseling experience with a large Parkinson disease cohort is used as a starting point to question the state of clinical and nonclinical practice in disclosing this unusual connection We conclude that more research and discussion are needed to inform practice regarding the crossroads of Gaucher and Parkinson disease.

Heart valve disease associated with treatment with ergot-derived dopamine agonists: a clinical and echocardiographic study of patients with Parkinson's disease.

PubMed

Rasmussen, V G; Poulsen, S H; Dupont, E; Østergaard, K; Safikhany, G; Egeblad, H

2008-01-01

To elucidate the association between treatment with ergot-derived dopamine agonists (EDDA) and valvular abnormalities amongst patients with idiopathic Parkinson's disease (IPD) and secondly, to analyse the yield of clinical screening for valvular heart disease. A cross-sectional controlled study. The cohort of IPD patients treated in the outpatient clinic, Department of Neurology, Aarhus University Hospital, Denmark. A total of 138 IPD patients [median age 64 (39-87) years, 62% men] treated with either EDDA (n = 85) or non-EDDA (n = 53) for at least 6 months. Interventions. Patients were screened for valvular heart disease by clinical means and by examiner-blinded echocardiography. Main outcome measure was valvular regurgitation revealed by echocardiography. Severe aortic regurgitation (n = 4) or moderate aortic (n = 12), mitral (n = 3) or tricuspidal valve regurgitation (n = 5) was found in 22 EDDA patients (25.9%). Two patients had coexistent moderate mitral and tricuspid valvular regurgitation. Two non-EDDA patients had moderate valve insufficiency (3.8%, P < 0.05). The adjusted relative risk for at least moderate valve insufficiency in the EDDA patients was 7.2% (P < 0.05). The sensitivity of detecting at least moderate valvular disease by cardiac murmur, dyspnoea, or the heart failure marker NT-proBNP (natriuretic peptide) was 62% for the neurologists and 93% for the cardiologist but with equally low specificity (30-35%). EDDA was associated with a clinically important and statistically significant risk of at least moderate valve regurgitation. Clinical screening for valve disease was inadequate and it seems advisable to offer EDDA patients control with echocardiography.

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

PubMed Central

Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin

2016-01-01

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era. PMID:27819412

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

PubMed

Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

2016-10-01

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review

PubMed Central

2012-01-01

There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice. PMID:23259710

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

PubMed Central

Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.

2015-01-01

Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

PubMed

Sanchez-Barcelo, Emilio J; Rueda, Noemi; Mediavilla, María D; Martinez-Cue, Carmen; Reiter, Russel J

2017-11-20

Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Detection of borreliae in archived sera from patients with clinically suspect Lyme disease.

PubMed

Lee, Sin Hang; Vigliotti, Jessica S; Vigliotti, Veronica S; Jones, William; Shearer, David M

2014-03-11

The diagnoses of Lyme disease based on clinical manifestations, serological findings and detection of infectious agents often contradict each other. We tested 52 blind-coded serum samples, including 20 pre-treatment and 12 post-treatment sera from clinically suspect Lyme disease patients, for the presence of residual Lyme disease infectious agents, using nested PCR amplification of a signature segment of the borrelial 16S ribosomal RNA gene for detection and direct DNA sequencing of the PCR amplicon for molecular validation. These archived sera were split from the samples drawn for the 2-tier serology tests performed by a CDC-approved laboratory, and are used as reference materials for evaluating new diagnostic reagents. Of the 12 post-treatment serum samples, we found DNA evidence of a novel borrelia of uncertain significance in one, which was also positive for the 2-tier serology test. The rest of the post-treatment sera and all 20 control sera were PCR-negative. Of the 20 pre-treatment sera from clinically suspect early Lyme disease patients, we found Borrelia miyamotoi in one which was 2-tier serology-negative, and a Borrelia burgdorferi in two-one negative and one positive for 2-tier serology. We conclude that a sensitive and reliable DNA-based test is needed to support the diagnosis of Lyme disease and Lyme disease-like borreliosis.

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

PubMed Central

Nanda, Ranjan; Chakraborty, Trinad

2013-01-01

SUMMARY This review article introduces the significance of testing of volatile organic compounds (VOCs) in clinical samples and summarizes important features of some of the technologies. Compared to other human diseases such as cancer, studies on VOC analysis in cases of infectious diseases are limited. Here, we have described results of studies which have used some of the appropriate technologies to evaluate VOC biomarkers and biomarker profiles associated with infections. The publications reviewed include important infections of the respiratory tract, gastrointestinal tract, urinary tract, and nasal cavity. The results highlight the use of VOC biomarker profiles resulting from certain infectious diseases in discriminating between infected and healthy subjects. Infection-related VOC profiles measured in exhaled breath as well as from headspaces of feces or urine samples are a source of information with respect to disease detection. The volatiles emitted in clinical matrices may on the one hand represent metabolites of the infecting pathogen or on the other hand reflect pathogen-induced host responses or, indeed, a combination of both. Because exhaled-breath samples are easy to collect and online instruments are commercially available, VOC analysis in exhaled breath appears to be a promising tool for noninvasive detection and monitoring of infectious diseases. PMID:23824368

Clinical validity of a disease-specific health status questionnaire: the peripheral artery questionnaire.

PubMed

Hoeks, Sanne E; Smolderen, Kim G; Scholte Op Reimer, Wilma J M; Verhagen, Hence J M; Spertus, John A; Poldermans, Don

2009-02-01

Measuring patient-centered outcomes is becoming increasingly important in patients with peripheral arterial disease (PAD), both as a means of determining the benefits of treatment and as an aid for disease management. In order to monitor health status in a reliable and sensitive way, the disease-specific measure Peripheral Artery Questionnaire (PAQ) was developed. However, to date, its correlation with traditional clinical indices is unknown. The primary aim of this study was to better establish the clinical validity of the PAQ by examining its association with functional indices related to PAD. Furthermore, we hypothesized that the clinical validity of this disease-specific measure is better as compared with the EuroQol-5-dimensional (EQ-5D), a standardized generic instrument. Data on 711 consecutive PAD patients undergoing surgery were collected from 11 Dutch hospitals in 2004. At 3-year follow-up, questionnaires including the PAQ, EQ-5D, and EuroQol-Visual Analogue Scale (EQ VAS) were completed in 84% of survivors. The PAQ was analyzed according to three domains, as established by a factor analyses in the Dutch population, and the summary score. Baseline clinical indices included the presence and severity of claudication intermittent (CI) and the Lee Cardiac Risk Index. All three PAQ domains (Physical Function, Perceived Disability, and Treatment Satisfaction) were significantly associated with CI symptoms (P values < .001-.008). Patients with claudication had significant lower PAQ summary scores as compared with asymptomatic patients (58.6 +/- 27.8 vs 68.6 +/- 27.8, P = < .001). Furthermore, the PAQ summary score and the subscale scores for Physical Functioning and Perceived Disability demonstrated a clear dose-response relation for walking distance and the Lee Risk Index (P values < .001-.031). With respect to the generic EQ-5D, the summary EQ-5D index was associated with CI (0.81 +/- 0.20 vs 0.76 +/- 0.24, P = .031) but not with walking distance (P = .128

Norrie disease resulting from a gene deletion: clinical features and DNA studies.

PubMed

Donnai, D; Mountford, R C; Read, A P

1988-02-01

We describe a family in which two boys with Norrie disease have a deletion of the DXS7 locus. The deletion does not extend as far distally as the OTC or DXS84 loci. A full clinical description of the patients is given to help establish the range of manifestations of Norrie disease. There is no evidence of any other X linked disease in our patients.

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

PubMed

Okamoto, Kenichi W; Gould, Fred; Lloyd, Alun L

2016-03-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases

PubMed Central

Okamoto, Kenichi W.; Gould, Fred; Lloyd, Alun L.

2016-01-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences—consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest

Clinical presentation and risk factors of inflammatory bowel disease in Sri Lanka.

PubMed

Weerasekara, Deepaka; Fernando, Neluka; Meedin, F; Holton, John; Fernando, D

2011-01-01

There have been very few studies on inflammatory bowel disease (IBD) in Sri Lanka. This study was undertaken to determine the clinical presentation and whether a western style diet or infection with geo-helminths were associated with the condition. Three questionnaires were given to the patients: one relating to diet, one relating to clinical presentation and one relating to quality of life. The disease was confirmed endoscopically and histologically. Faeces were examined for parasites. Forty four patients were enrolled (43-ulcerative colitis; 1-Crohn's Disease). All but one had ulcerative colitis. Most had no family history of disease. The peak age of onset was 21-40 y and 63% gave a history of more than 6 months symptoms prior to diagnosis. Clinical presentation was similar to cases in western countries although milder with less severe life-events. None of them had undergone surgery. All patients ate a rice-based diet and none ate bread made of refined flour. Only 2 patient was infected with a geo-helminth. Eating bread made of refined flour is not related to development of IBD in these patients. The prevalence of geo-helminths in the study population corresponded to the general population average. Delay in diagnosis occurs because of an initial assumption that the cause of symptoms is infective. A National Register of non-infectious gastrointestinal disease would aid the epidemiology and allocation of funding to this inflammatory condition.

Clinical association: Lyme disease and Guillain-Barre syndrome.

PubMed

Patel, Kinner; Shah, Siddharth; Subedi, Dinesh

2017-10-01

Guillain-Barre Syndrome (GBS) is a life-threatening condition in which patients may present to the Emergency Department in respiratory distress leading to death. The early identification and treatment of such a condition is paramount in preventing mortality. While there are many infections associated with GBS, the association with Lyme disease is uncommon. Through our case we aim to highlight Borrelia burgdorferi as an important antecedent infection associated with the development of GBS. In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease

PubMed Central

Cairns, N.J.; Grossman, M.; Arnold, S.E.; Burn, D.J.; Jaros, E.; Perry, R.H.; Duyckaerts, C.; Stankoff, B.; Pillon, B.; Skullerud, K.; Cruz-Sanchez, F.F.; Bigio, E.H.; Mackenzie, I.R.A.; Gearing, M.; Juncos, J.L.; Glass, J.D.; Yokoo, H.; Nakazato, Y.; Mosaheb, S.; Thorpe, J.R.; Uryu, K.; Lee, V.M.-Y.; Trojanowski, J.Q.

2009-01-01

Background Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity. Objective To assess the spectrum of the clinical and neuropathological features in 10 NIFID cases. Methods Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted. Results The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and α-internexin. Conclusion NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies. PMID:15505152

Task shifting to clinical officer-led echocardiography screening for detecting rheumatic heart disease in Malawi, Africa.

PubMed

Sims Sanyahumbi, Amy; Sable, Craig A; Karlsten, Melissa; Hosseinipour, Mina C; Kazembe, Peter N; Minard, Charles G; Penny, Daniel J

2017-08-01

Echocardiographic screening for rheumatic heart disease in asymptomatic children may result in early diagnosis and prevent progression. Physician-led screening is not feasible in Malawi. Task shifting to mid-level providers such as clinical officers may enable more widespread screening. Hypothesis With short-course training, clinical officers can accurately screen for rheumatic heart disease using focussed echocardiography. A total of eight clinical officers completed three half-days of didactics and 2 days of hands-on echocardiography training. Clinical officers were evaluated by performing screening echocardiograms on 20 children with known rheumatic heart disease status. They indicated whether children should be referred for follow-up. Referral was indicated if mitral regurgitation measured more than 1.5 cm or there was any measurable aortic regurgitation. The κ statistic was calculated to measure referral agreement with a paediatric cardiologist. Sensitivity and specificity were estimated using a generalised linear mixed model, and were calculated on the basis of World Heart Federation diagnostic criteria. The mean κ statistic comparing clinical officer referrals with the paediatric cardiologist was 0.72 (95% confidence interval: 0.62, 0.82). The κ value ranged from a minimum of 0.57 to a maximum of 0.90. For rheumatic heart disease diagnosis, sensitivity was 0.91 (95% confidence interval: 0.86, 0.95) and specificity was 0.65 (95% confidence interval: 0.57, 0.72). There was substantial agreement between clinical officers and paediatric cardiologists on whether to refer. Clinical officers had a high sensitivity in detecting rheumatic heart disease. With short-course training, clinical officer-led echo screening for rheumatic heart disease is a viable alternative to physician-led screening in resource-limited settings.

Clinical, Dopaminergic, and Metabolic Correlations in Parkinson Disease: A Dual-Tracer PET Study.

PubMed

Liu, Feng-Tao; Ge, Jing-Jie; Wu, Jian-Jun; Wu, Ping; Ma, Yilong; Zuo, Chuan-Tao; Wang, Jian

2018-05-31

Neuroimaging indicators of Parkinson disease have been developed and applied in clinical practices. Dopaminergic imaging reflects nigrostriatal dopaminergic dysfunction, and metabolic network imaging offers disease-related metabolic changes at a system level. We aimed to elucidate the association between Parkinsonian symptoms and neuroimaging, and interactions between different imaging techniques. We conducted a dual-tracer PET study for the combined assessments of dopaminergic binding (C-CFT) and glucose metabolism (F-FDG) in 103 participants with Parkinson disease (65 male and 38 female subjects). The detailed clinical rating scores were systematically collected in all members. The interactions among dopaminergic bindings, metabolic changes, and clinical manifestations were evaluated at voxel, regional, and network levels. Striatal DAT binding correlated with akinesia-rigidity (P < 0.001) but not with tremor; the metabolic PET imaging, nonspecific to the dopaminergic dysfunction, disclosed a set of brain regions correlating with the cardinal symptoms, including tremor. In addition, the unilateral symptom correlated with the contralateral nigrostriatal dopamine loss, but with bilateral metabolic changes, suggesting their differences in the application of disease-related mechanistic studies. Further imaging-imaging correlation study revealed that dopaminergic dysfunction correlated with widely distributed metabolic changes in Parkinson disease, and the modest correlations supported the findings on the clinical-imaging correlation. In this dual-tracer PET study, we demonstrated the robust interactions among dopaminergic dysfunction, metabolic brain changes and clinical manifestations at voxel, regional, and network levels. Our findings might promote the understanding in the proper application of dopaminergic and metabolic PET imaging in Parkinson disease and offer more evidence in support of Parkinsonian pathophysiological mechanisms.This is an open-access article

Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

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

Mullan, M.; Bennett, C.; Figueredo, C.

1995-02-27

Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

Defining end-stage renal disease in clinical trials: a framework for adjudication.

PubMed

Agarwal, Rajiv

2016-06-01

Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Clinical value of natriuretic peptides in chronic kidney disease.

PubMed

Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

2015-01-01

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Analysis of Participant Withdrawal in Huntington Disease Clinical Trials.

PubMed

Banno, Haruhiko; Andrzejewski, Kelly L; McDermott, Michael P; Murphy, Alyssa; Majumder, Madhurima; de Blieck, Elisabeth A; Auinger, Peggy; Cudkowicz, Merit E; Atassi, Nazem

2017-01-01

Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials. We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal. Analyses of participant withdrawal were performed for three randomized, double-blind, placebo-controlled trials including the CARE-HD (coenzyme Q10 and remacemide in HD, n = 347), DOMINO (pilot study of minocycline in HD, n = 114), and 2CARE (coenzyme Q10 in HD, n = 609) trials. Reasons for withdrawal were obtained by review of textual data in the study databases. Participant demographic and clinical characteristics were analyzed as potential predictors of time to withdrawal using Cox-proportional hazards models. Estimated probabilities of withdrawal at 12 months were 2.9% for CARE-HD, 10.5% for DOMINO, and 5.9% for 2CARE. The top reasons for withdrawal (202 in total), expressed as mean percentage across the three trials, were loss to follow-up (23.2%), death (15.9%), and loss of interest/desire to participate (15.2%). Baseline and time-dependent variables associated with time to withdrawal were mainly motor, behavioral, and functional scores. Age, gender, ethnicity, and educational level were not associated with time to withdrawal in any of the three studies. The estimated withdrawal probability at 12 months ranged from 2.9% to 10.5% in the three HD trials considered here. A possible strategy to improve retention of participants in future HD clinical trials is to enroll individuals with higher baseline functional and behavioral status.

Multiscale Modeling of Drug-induced Effects of ReDuNing Injection on Human Disease: From Drug Molecules to Clinical Symptoms of Disease

NASA Astrophysics Data System (ADS)

Luo, Fang; Gu, Jiangyong; Zhang, Xinzhuang; Chen, Lirong; Cao, Liang; Li, Na; Wang, Zhenzhong; Xiao, Wei; Xu, Xiaojie

2015-05-01

ReDuNing injection (RDN) is a patented traditional Chinese medicine, and the components of it were proven to have antiviral and important anti-inflammatory activities. Several reports showed that RDN had potential effects in the treatment of influenza and pneumonia. Though there were several experimental reports about RDN, the experimental results were not enough and complete due to that it was difficult to predict and verify the effect of RDN for a large number of human diseases. Here we employed multiscale model by integrating molecular docking, network pharmacology and the clinical symptoms information of diseases and explored the interaction mechanism of RDN on human diseases. Meanwhile, we analyzed the relation among the drug molecules, target proteins, biological pathways, human diseases and the clinical symptoms about it. Then we predicted potential active ingredients of RDN, the potential target proteins, the key pathways and related diseases. These attempts may offer several new insights to understand the pharmacological properties of RDN and provide benefit for its new clinical applications and research.

False allegations of abuse and Munchausen syndrome by proxy.

PubMed Central

Meadow, R

1993-01-01

Fourteen children from seven families are reported for whom false allegations of abuse were made by the mother. Twelve children were alleged to have incurred sexual abuse, one both sexual and physical abuse, and one physical abuse alone. Thirteen of the children had incurred, or were currently victims of, factitious illness abuse invented by the mother. The one child with no history of factitious illness abuse had a sibling who had incurred definite factitious illness abuse. The false allegations of abuse did not occur in the context of parental separation, divorce, or custody disputes concerning the children. They occurred in the context of Munchausen syndrome by proxy abuse. The age of the children, 3 to 9 years, was older than the usual age for Munchausen syndrome by proxy abuse. The mother was the source of the false allegations and was the person who encouraged or taught six of the children to substantiate allegations of sexual abuse. PMID:8503664

Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

PubMed Central

Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

2014-01-01

The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities

CEDRIC: a computerized chronic disease management system for urban, safety net clinics.

PubMed

Ogunyemi, Omolola; Mukherjee, Sukrit; Ani, Chizobam; Hindman, David; George, Sheba; Ilapakurthi, Ramarao; Verma, Mary; Dayrit, Melvin

2010-01-01

To meet the challenge of improving health care quality in urban, medically underserved areas of the US that have a predominance of chronic diseases such as diabetes, we have developed a new information system called CEDRIC for managing chronic diseases. CEDRIC was developed in collaboration with clinicians at an urban safety net clinic, using a community-participatory partnered research approach, with a view to addressing the particular needs of urban clinics with a high physician turnover and large uninsured/underinsured patient population. The pilot implementation focuses on diabetes management. In this paper, we describe the system's architecture and features.

An Eight-Year Clinic Experience with Clozapine Use in a Parkinson’s Disease Clinic Setting

PubMed Central

Hack, Nawaz; Fayad, Sarah M.; Monari, Erin H.; Akbar, Umer; Hardwick, Angela; Rodriguez, Ramon L.; Malaty, Irene A.; Romrell, Janet; Shukla, Aparna A. Wagle.; McFarland, Nikolaus; Ward, Herbert E.; Okun, Michael S.

2014-01-01

Background To examine our eight year clinic-based experience in a Parkinson’s disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). Methods The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. Results There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45–87 years (mean 68.3±10.15), disease duration of 17–240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = −0.36, p<0.01) and H&Y score (r = −0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). Conclusions This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting. PMID:24646688

Norrie disease resulting from a gene deletion: clinical features and DNA studies.

PubMed Central

Donnai, D; Mountford, R C; Read, A P

1988-01-01

We describe a family in which two boys with Norrie disease have a deletion of the DXS7 locus. The deletion does not extend as far distally as the OTC or DXS84 loci. A full clinical description of the patients is given to help establish the range of manifestations of Norrie disease. There is no evidence of any other X linked disease in our patients. Images PMID:3162283

Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

PubMed

Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

2018-01-19

This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

Early clinics of the cardiac forms of Chagas' disease: Discovery and study of original medical files (1909-1915).

PubMed

Gachelin, Gabriel; Bestetti, Reinaldo B

2017-10-01

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described. Copyright © 2017 Elsevier B.V. All rights reserved.

[The clinical picture and stability of non-cognitive symptoms in patients with Alzheimer's disease].

PubMed

Haupt, M; Jänner, M; Stierstorfer, A; Kretschmar, C

1998-05-01

The purpose of this study was to investigate noncognitive symptoms in Alzheimer's disease in order to identify symptom patterns and to study stability of such patterns prospectively. Furthermore, variables were examined which could be associated with certain types of symptom patterns or could be predictors of change of these patterns. Forty-eight patients with the clinical diagnosis of probable Alzheimer's disease were included in this study and were assessed weekly over a three-week period. Noncognitive symptoms were rated according to the Behavioral Abnormalities in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Dementia Mood Assessment Scale (DMAS) and to a set of items specifically assessing misidentifications. By means of principal component factor analysis different noncognitive symptom patterns were obtained yielding a four-factor solution. They were mapped as rational domains with respect to clinical experience: 'depression', 'apathy', 'psychotic symptoms/aggression', 'misidentifications/agitation'. Demographic and clinical variables were not associated with the factor solutions and did not predict change of the factor values. The results demonstrate that in Alzheimer's disease there are distinct noncognitive symptom patterns with at least short-term prospective stability. None of the examined clinical variables, such as age at entry, the status of the patients (outpatient or inpatient) or dementia severity, exerted substantial influence on the noncognitive symptom patterns. Further investigations should concentrate on the pathological and prognostical correlates of noncognitive symptom patterns in Alzheimer's disease.

Periodontitis in pregnancy: clinical and serum antibody observations from a baboon model of ligature-induced disease.

PubMed

Cappelli, D; Steffen, M J; Holt, S C; Ebersole, J L

2009-07-01

Chronic oral infections that elicit host responses leading to periodontal disease are linked with various sequelae of systemic diseases. This report provides seminal information on the clinical and adaptive immunologic characteristics of a baboon model of ligature-induced periodontitis during pregnancy. Female Papio anubis were evaluated for periodontal health at baseline. Ligatures were tied around selected teeth to initiate oral inflammation and periodontitis. Then the animals were bred. At midpregnancy ( approximately 90 days), a clinical evaluation was performed, and additional ligatures were tied on teeth in the contralateral quadrants to maintain progressing periodontitis throughout pregnancy. A final clinical evaluation was done for all experimental teeth after delivery, and ligatures were removed. Serum was collected at all sampling intervals for the determination of antibody levels to a group of 20 oral bacteria. Unligated animals served as controls. At baseline, 16% of animals exhibited minimal plaque and gingival inflammation without periodontal disease. The remaining baboons demonstrated varying levels of inflammation/bleeding, and approximately 20% of the population had periodontal pocketing (>3 mm). Ligated animals expressed increased levels of inflammation and increased probing depths and clinical attachment loss (AL) and could be stratified into multiple subsets postligation based upon changes in clinical parameters at midpregnancy and at delivery. Baboons were categorized into disease susceptibility groups (periodontal disease susceptibility 1 through 4) that described the extent/severity of induced disease during pregnancy. Control animals showed minimal periodontal changes during gestation. Significant differences in serum antibody to multiple oral bacteria were found in animals presenting with periodontitis at baseline and during the 6 months of ligature-induced disease. A significant correlation to antibody to P. gingivalis, which was sustained

Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

PubMed

Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

2017-08-01

Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

PubMed Central

Tye-Din, J A; Cameron, D J S; Daveson, A J; Day, A S; Dellsperger, P; Hogan, C; Newnham, E D; Shepherd, S J; Steele, R H; Wienholt, L; Varney, M D

2015-01-01

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results. PMID:25827511

New Insights in the Clinical Understanding of Behçet's Disease

PubMed Central

Cho, Sung Bin; Cho, Suhyun

2012-01-01

Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness. PMID:22187230

Whipple's disease. Report of five cases with different clinical features.

PubMed

Ferrari, M de L; Vilela, E G; Faria, L C; Couto, C A; Salgado, C J; Leite, V R; Brasileiro Filho, G; Bambirra, E A; Mendes, C M; Carvalho, S de C; de Oliveira, C A; da Cunha, A S

2001-01-01

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

Bullous dermatitis artefacta.

PubMed

Sokumbi, Olayemi; Comfere, Nneka I; McEvoy, Marian T; Peters, Margot S

2013-02-01

Bullous artefactual dermatoses are rare and may be induced by various techniques, including chemicals, heat, or electrical current. Proving a factitial etiology and identifying the mechanism of injury may be difficult. We describe the clinical features and histopathology of 2 patients with bullous disease induced by electrical current or heat. Physical examination in both patients demonstrated geometrically shaped tense bullae. Skin biopsies revealed epidermal necrosis overlying a pauci-inflammatory subepidermal cleft, with homogenization of underlying superficial dermal collagen. In 1 of the 2 patients, there was prominent vertical elongation of keratinocyte nuclei and also of cytoplasmic processes. Direct immunofluorescence study of skin plus testing of serum by indirect immunofluorescence and enzyme-linked immunosorbent assay for BP180 and BP230 antibodies revealed no evidence for immunobullous disease in either patient. Vertical elongation of keratinocyte nuclei, often attributed to a polarization effect of electrical current, is characteristic of electrical burn but also may be induced by thermal injury. These 2 patients highlight the importance of histopathology in confirming a diagnosis of bullous dermatitis artefacta.

Clinical utility of bone turnover markers in the management of common metabolic bone diseases in adults.

PubMed

Glendenning, Paul; Chubb, S A Paul; Vasikaran, Samuel

2018-06-01

Bone turnover marker (BTMs) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTMs reflect bone loss. However, lack of adequate data precludes their use in individual patients for fracture risk assessment in clinical practice. The rapid and large changes in BTMs following anti-resorptive and anabolic therapies for osteoporosis treatment indicate they may be useful for monitoring therapy in clinical practice. The offset of drug effect on BTMs could be helpful for adjudicating the duration of bisphosphonate drug holidays. BTMs may offer useful additional data in skeletal diseases that are typically characterised by increased bone remodelling: chronic kidney disease (CKD), primary hyperparathyroidism (PHPT) and Paget's disease. In CKD, bone specific alkaline phosphatase (bAP) is currently endorsed for use for the assessment of mineral bone disease. The role of BTMsin predicting the bone mineral density response to successful parathyroidectomy in PHPT shows some utility but the data are not consistent and studies are limited in size and/or duration. In Paget's disease of bone, BTMs are used to confirm diagnosis, evaluate extent of disease or degree of activity and for monitoring the response to bisphosphonate treatment. Whilst BTMs are currently used in specific clinical practice instances when investigating or managing metabolic bone disease, further data are needed to consolidate their clinical use where evidence of utility is limited. Copyright © 2018 Elsevier B.V. All rights reserved.

Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment

PubMed Central

Buliman, A; Tataranu, LG; Paun, DL; Mirica, A; Dumitrache, C

2016-01-01

Cushing’s disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing’s disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing’s disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing’s disease using the most recent available guidelines. PMID:27974908

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

PubMed Central

Aygun, Meral Gunay-; Hildebrandt, Friedhelm

2011-01-01

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases. PMID:21926397

The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer's Disease.

PubMed

Martins, Ian James

2016-03-31

The early diagnosis of Alzheimer's disease (AD) has become important to the reversal and treatment of neurodegeneration, which may be relevant to premature brain aging that is associated with chronic disease progression. Clinical proteomics allows the detection of various proteins in fluids such as the urine, plasma, and cerebrospinal fluid for the diagnosis of AD. Interest in lipidomics has accelerated with plasma testing for various lipid biomarkers that may with clinical proteomics provide a more reproducible diagnosis for early brain aging that is connected to other chronic diseases. The combination of proteomics with lipidomics may decrease the biological variability between studies and provide reproducible results that detect a community's susceptibility to AD. The diagnosis of chronic disease associated with AD that now involves genomics may provide increased sensitivity to avoid inadvertent errors related to plasma versus cerebrospinal fluid testing by proteomics and lipidomics that identify new disease biomarkers in body fluids, cells, and tissues. The diagnosis of AD by various plasma biomarkers with clinical proteomics may now require the involvement of lipidomics and genomics to provide interpretation of proteomic results from various laboratories around the world.

Telomeres and age-related disease: how telomere biology informs clinical paradigms

PubMed Central

Armanios, Mary

2013-01-01

Telomere length shortens with age and predicts the onset of replicative senescence. Recently, short telomeres have been linked to the etiology of degenerative diseases such as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis. These disorders have recognizable clinical manifestations, and the telomere defect explains their genetics and informs the approach to their treatment. Here, I review how telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions. I also critically examine nuances of interpreting telomere length measurement in clinical studies. PMID:23454763

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications.

PubMed

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

: Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.

Effect of study partner on the conduct of Alzheimer disease clinical trials

PubMed Central

Raman, Rema; Ernstrom, Karin; Aisen, Paul; Karlawish, Jason

2013-01-01

Objective: Alzheimer disease (AD) dementia clinical trials require 2 participants: a patient and a study partner. We assessed the prevalence of study partner types and how these types associate with patient-related outcome measures. Methods: Retrospective analyses of 6 Alzheimer’s Disease Cooperative Study (ADCS) randomized clinical trials were conducted. Study partners were categorized as spouse, adult child, or other. Prevalence of study partner type and associations between study partner type and trial outcomes including study completion and placebo decline on the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–cognitive subscale, the Clinical Dementia Rating scale Sum of the Boxes score, and the ADCS–Activities of Daily Living were examined. Results: More participants (67%) enrolled with spouses than adult children (26%) or other study partners (7%). Participants with spouse partners had a lower dropout rate (25%) than those with adult child (32%) or other study partners (34%); only the difference vs others was statistically significant. Participants with adult child and other partners randomized to placebo performed worse at baseline than those with spouse partners on the ADCS–Activities of Daily Living (p = 0.04), but were not different at 18 months. There were no differences at baseline for the Mini-Mental State Examination, Clinical Dementia Rating scale Sum of the Boxes score, or Alzheimer’s Disease Assessment Scale–cognitive subscale. In multivariate models of the rates of change over time among placebo participants, no differences among study partner groups reached statistical significance. Conclusions: Patients with nonspouse caregivers less frequently participate in AD dementia trials. Increased enrollment of AD patients with nonspouse caregivers may require additional recruitment and retention strategies. PMID:23255824

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

PubMed Central

Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

2015-01-01

Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

α-Synuclein oligomers and clinical implications for Parkinson disease

PubMed Central

Kalia, Lorraine V.; Kalia, Suneil K.; McLean, Pamela J.; Lozano, Andres M.; Lang, Anthony E.

2012-01-01

Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications. PMID:23225525

Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

PubMed

Kowalski, Marek L; Wardzyńska, Aleksandra; Makowska, Joanna S

2016-11-01

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical and molecular genetic features of Hb H and AE Bart's diseases in central Thai children.

PubMed

Traivaree, Chanchai; Boonyawat, Boonchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Photia, Apichat

2018-01-01

α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart's disease. This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand. Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart's disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed. A total of 76 pediatric patients with Hb H and AE Bart's diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart's disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non-deletional AE Bart's disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant. This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart's disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype-phenotype correlation.

Gallstone disease. The clinical manifestations of infectious stones.

PubMed

Smith, A L; Stewart, L; Fine, R; Pellegrini, C A; Way, L W

1989-05-01

Gallstones from 82 patients were examined under a scanning electron microscope for evidence of bacteria, and the findings were compared with the clinical manifestations of the disease. Bacteria were present in 68% of pigment stones and the pigment portions of 80% of composite stones. These gallstones were referred to as infectious stones. No bacteria were found in cholesterol gallstones. Acute cholangitis was diagnosed in 52% of patients with infectious stones and in 18% of patients with noninfectious stones. Over half of the patients with noninfectious stones presented with mild symptoms. Infectious stones were more often associated with a previous common duct exploration, an urgent operation, infected bile, a common duct procedure, and complications. These data show that gallstone disease is more virulent in patients whose gallstones contain bacteria.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

PubMed

Stallmach, A; Langbein, C; Atreya, R; Bruns, T; Dignass, A; Ende, K; Hampe, J; Hartmann, F; Neurath, M F; Maul, J; Preiss, J C; Schmelz, R; Siegmund, B; Schulze, H; Teich, N; von Arnim, U; Baumgart, D C; Schmidt, C

2016-12-01

Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks. © 2016 John Wiley & Sons Ltd.

Clinical management of pain and fatigue in Parkinson's disease.

PubMed

Del Sorbo, Francesca; Albanese, Alberto

2012-01-01

Pain and fatigue are part of the phenomenological spectrum of Parkinson's disease (PD). These non-motor symptoms can be as troublesome as motor symptoms, impact activities of daily living, and are often underdiagnosed. The recognition of pain and fatigue requires a high degree of clinical suspicion and is facilitated by the use of specific questionnaires and ancillary tests. This workup is highly valuable particularly considering that pain and fatigue in PD may be treatable. We review here the clinical manifestations and management of these non-motor symptoms. Their resolution can be challenging, as there is insufficient evidence concerning effective treatment options. Copyright © 2011 Elsevier Ltd. All rights reserved.

Updates on chikungunya epidemiology, clinical disease, and diagnostics.

PubMed

Sam, I-Ching; Kümmerer, Beate M; Chan, Yoke-Fun; Roques, Pierre; Drosten, Christian; AbuBakar, Sazaly

2015-04-01

Chikungunya virus (CHIKV) is an Aedes-borne alphavirus, historically found in Africa and Asia, where it caused sporadic outbreaks. In 2004, CHIKV reemerged in East Africa and spread globally to cause epidemics, including, for the first time, autochthonous transmission in Europe, the Middle East, and Oceania. The epidemic strains were of the East/Central/South African genotype. Strains of the Asian genotype of CHIKV continued to cause outbreaks in Asia and spread to Oceania and, in 2013, to the Americas. Acute disease, mainly comprising fever, rash, and arthralgia, was previously regarded as self-limiting; however, there is growing evidence of severe but rare manifestations, such as neurological disease. Furthermore, CHIKV appears to cause a significant burden of long-term morbidity due to persistent arthralgia. Diagnostic assays have advanced greatly in recent years, although there remains a need for simple, accurate, and affordable tests for the developing countries where CHIKV is most prevalent. This review focuses on recent important work on the epidemiology, clinical disease and diagnostics of CHIKV.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

PubMed

Burns, J C; Wiggins, J W; Toews, W H; Newburger, J W; Leung, D Y; Wilson, H; Glodé, M P

1986-11-01

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Prevalence of clinical abnormalities in cats found to have nonneoplastic middle ear disease at necropsy: 59 cases (1991-2007).

PubMed

Schlicksup, Michael D; Van Winkle, Thomas J; Holt, David E

2009-10-01

To determine the prevalence of nonneoplastic middle ear disease among cats undergoing necropsy and the prevalence of clinical abnormalities in cats in which nonneoplastic middle ear disease was identified. Retrospective case series. 59 cats that underwent necropsy between January 1991 and August 2007. Medical records were searched to identify cats in which nonneoplastic middle ear disease was identified at necropsy. For cats included in the study, data that were recorded included signalment, initial complaint, whether the cat had any clinical signs of middle or external ear disease, whether the cat had upper respiratory tract disease, necropsy diagnosis, gross appearance of the bullae, and reason for euthanasia. Signs of middle ear disease that were considered included unilateral peripheral vestibular disease without motor deficits, Horner syndrome, and facial nerve paralysis. Of the 3,442 cats that underwent necropsy during the study period, 59 (1.7%) had nonneoplastic middle ear disease. Six of the 59 (10%) cats, including 1 cat that was affected bilaterally, had clinical signs of middle ear disease. Of these, 5 had signs of unilateral peripheral vestibular disease, and 1 had Horner syndrome. Results suggested that most cats with nonneoplastic middle ear disease did not have associated clinical signs. Findings may be of clinical relevance for cats in which middle ear disease is identified as an incidental finding during computed tomography or magnetic resonance imaging for unrelated diseases.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications.

PubMed

Christidi, Foteini; Migliaccio, Raffaella; Santamaría-García, Hernando; Santangelo, Gabriella; Trojsi, Francesca

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

PubMed Central

Santamaría-García, Hernando; Santangelo, Gabriella

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

[Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool sometimes useful in daily clinical practice of memory clinics for the diagnosis of complex cases].

PubMed

Magnin, E; Dumurgier, J; Bouaziz-Amar, E; Bombois, S; Wallon, D; Gabelle, A; Lehmann, S; Blanc, F; Bousiges, O; Hannequin, D; Jung, B; Miguet-Alfonsi, C; Quillard, M; Pasquier, F; Peoc'h, K; Laplanche, J-L; Hugon, J; Paquet, C

2017-04-01

The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

PubMed

Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PubMed

Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology

Incidental Lewy Body Disease: Clinical Comparison to a Control Cohort

PubMed Central

Adler, Charles H.; Connor, Donald J.; Hentz, Joseph G.; Sabbagh, Marwan N.; Caviness, John N.; Shill, Holly A.; Noble, Brie; Beach, Thomas G.

2010-01-01

Limited clinical information has been published on cases pathologically diagnosed with incidental Lewy body disease (ILBD). Standardized, longitudinal movement and cognitive data was collected on a cohort of subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program. Of 277 autopsied subjects who had antemortem clinical evaluations within the previous 3 years, 76 did not have Parkinson’s disease, a related disorder, or dementia of which 15 (20%) had ILBD. Minor extrapyramidal signs were common in subjects with and without ILBD. Cognitive testing revealed an abnormality in the ILBD group in the Trails B test only. ILBD cases had olfactory dysfunction; however, sample size was very small. This preliminary report revealed ILBD cases have movement and cognitive findings that for the most part were not out of proportion to similarly assessed and age-similar cases without Lewy bodies. Larger sample size is needed to have the power to better assess group differences. PMID:20175211

Clinic-cytologic study of conjunctivochalasis and its relation to thyroid autoimmune diseases: prospective cohort study.

PubMed

de Almeida, Sandra Flavia Fiorentini; de Sousa, Luciene B; Vieira, Luis A; Chiamollera, Maria I; Barros, Jeison de N

2006-08-01

To determine the prevalence of conjunctivochalasis in patients with immune thyroid diseases, to determine whether there is any association between the 2 diseases, and to determine cytologic study of conjunctivochalasis through the cytology impression test. A clinical prospective cohort study carried out by the External Diseases Department in the Ophthalmology Sector and the Thyroid Department in the Endocrinology Sector at Federal University of Sao Paulo (UNIFESP). The patients included were divided into 2 groups following these inclusion criteria: a control group of 25 patients without thyroid diseases, confirmed after clinical and laboratory examinations (thyroid hormones), or any other ocular diseases. The study group consisted of 31 patients with thyroid diseases, the diagnosis of which was confirmed by the Endocrinology Sector. The thyroidopathies included were autoimmune diseases but excluded nonautoimmune diseases. A protocol endorsed by the UNIFESP was followed, using clinical and ophthalmological history, biomicroscopy, and impression cytology. Fifty-two percent of patients without thyroid diseases and 88% of patients with thyroid diseases presented with conjunctivochalasis. The risk ratio was 1.705 (Pr > chi(2) = 0.0038), indicating that there is an association between them. For the impression cytology in inferior bulbar conjunctiva, there was an association between the result of the impression cytology and conjunctivochalasis (Pearson chi(2) = 10.1190 Pr = 0.006). The prevalence of conjunctivochalasis in patients with autoimmune thyroid diseases was 88%. Patients with autoimmune thyroidopathy presented higher percentages of conjunctivochalasis than the control group, confirming the association between them. The cytologic study showed the highest prevalence of abnormal surface features in eyes with conjunctivochalasis.

Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data.

PubMed

Mantzorou, Maria; Pavlidou, Eleni; Vasios, George; Tsagalioti, Eftychia; Giaginis, Constantinos

2018-06-01

Numerous clinical trials have investigated the potential beneficial effects of curcumin supplementation against several human chronic diseases. Up to now, it has been claimed that curcumin consumption may exert beneficial effects against several chronic diseases by promoting human health and preventing diseases. In this aspect, the present review aims to critically collect and in-depth summarize the most recent, well-designed clinical studies evaluating the potential beneficial effects of curcumin consumption on human health promotion and disease prevention. According to recent and well-designed clinical studies, curcumin consumption may benefit against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to exert a positive effect on people suffering from various types of cancer, fatty liver disease, depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome. Due to the strong heterogeneity among the clinical studies concerning the exact effective curcumin dose and formulation, as well as the recommended treatment duration for each chronic disease, no precise and definitive conclusions could be drawn. Further large-scale prospective studies are strongly recommended, being well-designed as far as follow-up times, dosage, formulation, and duration of curcumin supplementation are concerned. Moreover, potential confounders in each specific chronic disease should carefully be taken into account in future studies. Copyright © 2018 John Wiley & Sons, Ltd.

Effectiveness of nurse-led cardiac clinics in adult patients with a diagnosis of coronary heart disease.

PubMed

Page, Tamara; Lockwood, Craig; Conroy-Hiller, Tiffany

2005-02-01

Background  Coronary heart disease is the major cause of illness and death in Western countries and this is likely to increase as the average age of the population rises. Consumers with established coronary heart disease are at the highest risk of experiencing further coronary events. Lifestyle measures can contribute significantly to a reduction in cardiovascular mortality in established coronary heart disease. Improved management of cardiac risk factors by providing education and referrals as required has been suggested as one way of maintaining quality care in patients with established coronary heart disease. There is a need to ascertain whether or not nurse-led clinics would be an effective adjunct for patients with coronary heart disease to supplement general practitioner advice and care. Objectives  The objective of this review was to present the best available evidence related to nurse-led cardiac clinics. Inclusion criteria  This review considered any randomised controlled trials that evaluated cardiac nurse-led clinics. In the absence of randomised controlled trials, other research designs such as non-randomised controlled trials and before and after studies were considered for inclusion. Participants were adults (18 years and older) with new or existing coronary heart disease. The interventions of interest to the review included education, assessment, consultation, referral and administrative structures. Outcomes measured included adverse event rates, readmissions, admissions, clinical and cost effectiveness, consumer satisfaction and compliance with therapy. Results  Based on the search terms used, 80 papers were initially identified and reviewed for inclusion; full reports of 24 of these papers were retrieved. There were no papers included that addressed cost effectiveness or adverse events; and none addressed the outcome of referrals. A critical appraisal of the 24 remaining papers identified a total of six randomised controlled trials that

Current Role of Blood and Urine Biomarkers in the Clinical Care of Adults with Congenital Heart Disease.

PubMed

Rajpal, Saurabh; Alshawabkeh, Laith; Opotowsky, Alexander R

2017-06-01

There is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease. These stand as challenges to systematic investigation and clinical application of biomarkers for adults with CHD. This paper reviews recent studies investigating the use of biomarkers in this population, with emphasis on biomarkers applied in clinical adult CHD care. A handful of biomarkers have been integrated into adult CHD practice, such as iron studies in cyanotic heart disease and stool alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan circulation. Use of kidney and liver tests has been studied in prognostication of adult CHD patients. A few other biomarkers like natriuretic peptides and troponins seem likely to provide useful information in other ACHD situations based on limited disease-specific data and extrapolation from acquired heart disease. More research is needed to support the robust validity of most existing clinical biomarkers in adult congenital cardiology practice. Until data from larger, prospectively enrolled cohorts are available, clinical use of biomarkers in these patients will require careful interpretation with attention to underlying pathophysiology, as well as detailed understanding of potential pitfalls of specific assays and clinical contexts.

Clinical spectrum of Castleman disease-associated neuropathy.

PubMed

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

2016-12-06

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

The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.

Clinical validation of the CHRONIOUS wearable system in patients with chronic disease.

PubMed

Bellos, Christos; Papadopoulos, Athanassios; Rosso, Roberto; Fotiadis, Dimitrios I

2013-01-01

The CHRONIOUS system defines a powerful and easy to use framework which has been designed to provide services to clinicians and their patients suffering from chronic diseases. The system is composed of a wearable shirt that integrate several body sensors, a portable smart device and a central sub-system that is responsible for the long term storage of the collected patient's data. A multi-parametric expert system is developed for the analysis of the collected data using intelligent algorithms and complex techniques. Apart for the vital signals, dietary habits, drug intake, activity data, environmental and biochemical parameters are recorded. The CHRONIOUS platform is validated through clinical trials in several medical centers and patient's home environments recruiting patients suffering from Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD) diseases. The clinical trials contribute in improving the system's accuracy, while Pulmonologists and Nephrologists experts utilized the CHRONIOUS platform to evaluate its efficiency and performance. The results of the utilization of the system were very encouraging. The CHRONIOUS system has been proven to be a well-validated real-time patient monitoring and supervision platform, providing a useful tool for the clinician and the patient that would contribute to the more effective management of chronic diseases.

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

PubMed Central

2016-01-01

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose. PMID:27721835

Mining a clinical data warehouse to discover disease-finding associations using co-occurrence statistics

PubMed Central

Cao, Hui; Markatou, Marianthi; Melton, Genevieve B.; Chiang, Michael F.; Hripcsak, George

2005-01-01

This paper applies co-occurrence statistics to discover disease-finding associations in a clinical data warehouse. We used two methods, χ2 statistics and the proportion confidence interval (PCI) method, to measure the dependence of pairs of diseases and findings, and then used heuristic cutoff values for association selection. An intrinsic evaluation showed that 94 percent of disease-finding associations obtained by χ2 statistics and 76.8 percent obtained by the PCI method were true associations. The selected associations were used to construct knowledge bases of disease-finding relations (KB-χ2, KB-PCI). An extrinsic evaluation showed that both KB-χ2 and KB-PCI could assist in eliminating clinically non-informative and redundant findings from problem lists generated by our automated problem list summarization system. PMID:16779011

Mining a clinical data warehouse to discover disease-finding associations using co-occurrence statistics.

PubMed

Cao, Hui; Markatou, Marianthi; Melton, Genevieve B; Chiang, Michael F; Hripcsak, George

2005-01-01

This paper applies co-occurrence statistics to discover disease-finding associations in a clinical data warehouse. We used two methods, chi2 statistics and the proportion confidence interval (PCI) method, to measure the dependence of pairs of diseases and findings, and then used heuristic cutoff values for association selection. An intrinsic evaluation showed that 94 percent of disease-finding associations obtained by chi2 statistics and 76.8 percent obtained by the PCI method were true associations. The selected associations were used to construct knowledge bases of disease-finding relations (KB-chi2, KB-PCI). An extrinsic evaluation showed that both KB-chi2 and KB-PCI could assist in eliminating clinically non-informative and redundant findings from problem lists generated by our automated problem list summarization system.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications

PubMed Central

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype–phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, ‘real-world’ experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines. PMID:29176389

Clinical Utility of Serologic Testing for Celiac Disease in Ontario

PubMed Central

2010-01-01

tests in the diagnosis celiac disease? What is the clinical validity of serologic tests in the diagnosis of celiac disease? The clinical validity was defined as the ability of the test to change diagnosis. What is the clinical utility of serologic tests in the diagnosis of celiac disease? The clinical utility was defined as the impact of the test on decision making. What is the budget impact of serologic tests in the diagnosis of celiac disease? What is the cost-effectiveness of serologic tests in the diagnosis of celiac disease? Methods Literature Search A literature search was performed on November 13th, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1st 2003 and November 13th 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria Inclusion Criteria Exclusion Criteria Studies that evaluated diagnostic accuracy, i.e., both sensitivity and specificity of serology tests in the diagnosis of celiac disease. Study population consisted of untreated patients with symptoms consistent with celiac disease. Studies in which both serologic celiac disease tests and small bowel biopsy (gold standard) were used in all subjects. Systematic reviews, meta-analyses, randomized controlled trials, prospective observational studies, and retrospective cohort studies. At least 20 subjects included in

Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease-Methodology and Clinical Applications.

PubMed

Diana, Tanja; Kahaly, George J

2018-05-02

Thyroid stimulating hormone receptor antibodies (TSHR-Ab) cause autoimmune hyperthyroidism and are prevalent in patients with related thyroid eye disease (TED). To provide a historical perspective on TSHR-Ab and to present evidence-based recommendations for clinical contemporary use. The authors review the recent literature pertaining to TSHR-Ab in patients with TED and describe the various immunoassays currently used for detecting TSHR-Ab and their clinical applications. We provide a historical summary and description of the various methods used to detect TSHR-Ab, foremost, the functional TSHR-Ab. Increasing experimental and clinical data demonstrate the clinical usefulness of cell-based bioassays for measurements of functional TSHR-Ab in the diagnosis and management of patients with autoimmune TED and in the characterization of patients with autoimmune-induced hyperthyroidism and hypothyroidism. Thyroid stimulating hormone receptor antibodies, especially the functional stimulating antibodies, are sensitive, specific, and reproducible biomarkers for patients with autoimmune TED and correlate well with clinical disease activity and clinical severity. Unlike competitive-binding assays, bioassays have the advantage of indicating not only the presence of antibodies but also their functional activity and potency. Measurement of TSHR-Ab (especially stimulating antibodies) is a clinically useful tool for the management of patients with TED.

Clinical economics review: medical management of inflammatory bowel disease.

PubMed

Ward, F M; Bodger, K; Daly, M J; Heatley, R V

1999-01-01

Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5-amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost-effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end-points. Macro-economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000-480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn's disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual's economic productivity.

Predictors for return to work for those with occupational respiratory disease: clinical and structural factors.

PubMed

Zoeckler, Jeanette M; Cibula, Donald A; Morley, Christopher P; Lax, Michael B

2013-12-01

Few occupational researchers have examined "return to work" among patients with work-related respiratory diseases. In addition, prior studies have emphasized individual patient characteristics rather than a more multi-dimensional approach that includes both clinical and structural factors. A retrospective chart review identified patients with occupational respiratory diseases in the Occupational Health Clinical Center, Syracuse, NY between 1991 and 2009. We assessed predictors of work status using an exploratory, sequential mixed methods research design, multinomial (n = 188) and Cox regressions (n = 130). The findings suggest that patients with an increased number of diagnoses, non-union members, and those who took more than a year before clinical presentation had significantly poorer work status outcomes, after adjusting for age, education level, and relevant diagnoses. Efforts to prevent slow return to work after developing occupational respiratory disease should recognize the importance of timely access to occupational health services, disease severity, union membership, and smoking status. © 2013 Wiley Periodicals, Inc.

Clinical and genetic characterization of the autoinflammatory diseases diagnosed in an adult reference center.

PubMed

Hernández-Rodríguez, José; Ruíz-Ortiz, Estíbaliz; Tomé, Adrià; Espinosa, Gerard; González-Roca, Eva; Mensa-Vilaró, Anna; Prieto-González, Sergio; Espígol-Frigolé, Georgina; Mensa, Josep; Cardellach, Francesc; Grau, Josep M; Cid, Maria C; Yagüe, Jordi; Aróstegui, Juan I; Cervera, Ricard

2016-01-01

Autoinflammatory diseases (AID) are usually diagnosed during the pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described. To assess the clinical and genetic characteristics of adult patients diagnosed with an AID in an adult referral center for AID. We retrospectively evaluated clinical and genetic features of adult patients (≥16 years) diagnosed with an AID or referred after AID diagnosis to the Clinical Unit of AID, at the Department of Autoimmune Diseases, Hospital Clínic of Barcelona, from 2008 to 2014. During the study period, a genetic study for suspected AID was requested to 90 patients at the Department of Autoimmune Diseases. A final diagnosis of monogenic AID was achieved in 17 patients (19% of patients tested). Five additional cases were diagnosed with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and 10 patients with AID were referred from other adult departments. Finally, a total of 32 patients with AID were finally diagnosed or monitored in our Clinical Unit. These included 12 (37.5%) familial Mediterranean fever, 6 (18.8%) tumour necrosis factor-receptor associated periodic syndrome, 8 (25%) cryopirin-associated periodic syndromes (Muckle-Wells syndrome [MWS] or overlap familial cold-associated periodic syndrome/MWS), 1 (3.1%) mevalonate kinase deficiency, and 5 (15.6%) PFAPA. Clinical evidence of disease-onset during childhood and adulthood was observed in 15 (47%) and 17 (53%) patients, respectively. Overall, the final diagnosis was obtained after a delay of a mean of 12 years (range 0-47 years). Compared to children, adult patients with AID in our series presented more frequently with non-severe manifestations and none of them developed amyloidosis during follow-up. Adult patients also carried higher proportion of low-penetrance mutations or polymorphisms and all genetic variants were presented in heterozygosis or as heterozygous compounds. Adult disease

Clinical Relationship between Cholestatic Disease and Pituitary-Dependent Hyperadrenocorticism in Dogs: A Retrospective Case Series.

PubMed

Kim, K-H; Han, S-M; Jeon, K-O; Kim, H-T; Li, Q; Ryu, M-O; Song, W-J; Park, S-C; Youn, H-Y

2017-03-01

A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. Sixty-five client-owned dogs with naturally occurring PDH. This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

In-hospital death and adverse clinical events in elderly patients according to disease clustering: the REPOSI study.

PubMed

Marengoni, A; Bonometti, F; Nobili, A; Tettamanti, M; Salerno, F; Corrao, S; Iorio, A; Marcucci, M; Mannucci, P M

2010-08-01

The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the effect of disease clusters on in-hospital death and adverse clinical events. A total of 86.7% of the patients were discharged, 8.3% were transferred to another hospital unit, and 5.0% died during hospitalization; 36.4% of the patients had at least one adverse clinical event. Patients affected by the clusters, including heart failure (HF) and either chronic renal failure (CRF) or chronic obstructive pulmonary disease, had a significant association with in-hospital death (OR, 4.3;95% confidence interval [CI], 1.6-11.5; OR, 2.9; 95% CI, 1.1-8.3, respectively), as well as patients affected by CRF and anemia (OR, 6.1; 95% CI, 2.3-16.2). The cluster including HF and CRF was also associated with adverse clinical events (OR, 3.5; 95% CI, 1.5-7.8). The effect of both HF and CRF and anemia and CRF on in-hospital death was additive. Several groups of older patients at risk of in-hospital death and adverse clinical events were identified according to disease clustering. Knowledge of the relationship among co-occurring diseases may help developing strategies to improve clinical practice and preventative interventions.

A retrospective study of dermatitis herpetiformis from an immunobullous disease clinic in north India.

PubMed

Handa, Sanjeev; Dabas, Garima; De, Dipankar; Mahajan, Rahul; Chatterjee, Debajyoti; Saika, Uma N; Radotra, Bishan D

2018-05-11

Indian data on dermatitis herpetiformis (DH) is not available. The aim of this study was to investigate the demographic and clinicopathological characteristics of patients with DH and to study its association with other autoimmune diseases. All data were collected from case record forms of patients registered in immunobullous disease clinic of our institute. The diagnosis was based on characteristic clinical and immuno/histopathological features. A total of 65 patients were included, which constituted 9.47% of the registered patients in the immunobullous disease clinic over 3.5 years. The male to female ratio was 1.4 : 1; the average age was 44.35 ± 15.52 years. Direct immunofluorescence showed granular IgA deposits at the papillary tips in 83.07% and basement membrane zone in 12.3% patients. Sixteen (24.1%) patients had associated celiac disease, and 15 (23.07%) patients had other autoimmune comorbidities such as hypothyroidism. Forty percent of patients on strict gluten-free diet achieved remission in 2 years, while 35.4% had frequent relapses as they continued gluten intake. Dermatitis herpetiformis is not a rare disease in northern India as previously believed. The clinical, histological, and immunopathological characteristics of Indian DH patients are similar to those reported in Caucasian populations. The limitations of our study include an absence of genetic testing for HLA-DQ2 or DQ8, nonavailability of kits for detecting IgA specific for epidermal transglutaminase (IgA eTG), and short follow-up period. © 2018 The International Society of Dermatology.

Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

NASA Astrophysics Data System (ADS)

Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

2013-03-01

Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials.

PubMed

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2018-03-14

Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

PubMed

Agosta, Federica; Altomare, Daniele; Festari, Cristina; Orini, Stefania; Gandolfo, Federica; Boccardi, Marina; Arbizu, Javier; Bouwman, Femke; Drzezga, Alexander; Nestor, Peter; Nobili, Flavio; Walker, Zuzana; Pagani, Marco

2018-05-01

To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.

[The clinical and pathologic features of Charcot-Marie-Tooth disease].

PubMed

Xiao, Bo; Xie, Jusheng; Yang, Xiaosu; Wu, Zhiguo; Xiao, Jianfeng; Li, Jing

2002-11-01

To study the clinical and pathological features of Charcot-Marie-Tooth disease (CMT). The general clinical data, the changes of neuroelectrophysiology and the pathological features of neural and muscular biopsy of 20 CMT patients were comprehensively analyzed. The clinical manifestations in the two types of CMT were nearly the same, but the changes of neuroelectrophysiology and the pathological characteristics of the neural and muscular biopsy in the two types were obviously different. 16 cases of CMT type 1 were characterized by decreased sensory nerve conduction velocity (SNCV < 30 m/s) and are associated with demyelinating hypertrophic neuropathy. 4 cases of CMT tylpe 2 were characterized by normal SNCV and associated with axonopathy. Neuroelectrophysiology and neural and muscular biopsy are important for the diagnosis of CMT.

Donepezil treatment and Alzheimer disease: can the results of randomized clinical trials be applied to Alzheimer disease patients in clinical practice?

PubMed

Tinklenberg, Jared R; Kraemer, Helena C; Yaffe, Kristine; Ross, Leslie; Sheikh, Javaid; Ashford, John W; Yesavage, Jerome A; Taylor, Joy L

2007-11-01

To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients. AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained. A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

PubMed

Provenzano, Frank A; Muraskin, Jordan; Tosto, Giuseppe; Narkhede, Atul; Wasserman, Ben T; Griffith, Erica Y; Guzman, Vanessa A; Meier, Irene B; Zimmerman, Molly E; Brickman, Adam M

2013-04-01

Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). The Alzheimer's Disease Neuroimaging Initiative public database. The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. Clinical AD diagnosis and WMH volume. Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. White matter hyperintensities contribute to the presentation of AD and, in the context of

Rare diseases in clinical endocrinology: a taxonomic classification system.

PubMed

Marcucci, G; Cianferotti, L; Beck-Peccoz, P; Capezzone, M; Cetani, F; Colao, A; Davì, M V; degli Uberti, E; Del Prato, S; Elisei, R; Faggiano, A; Ferone, D; Foresta, C; Fugazzola, L; Ghigo, E; Giacchetti, G; Giorgino, F; Lenzi, A; Malandrino, P; Mannelli, M; Marcocci, C; Masi, L; Pacini, F; Opocher, G; Radicioni, A; Tonacchera, M; Vigneri, R; Zatelli, M C; Brandi, M L

2015-02-01

Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

Clinical disease and laboratory abnormalities in free-ranging desert tortoises in California (1990-1995).

PubMed

Christopher, Mary M; Berry, Kristin H; Henen, Brian T; Nagy, Kenneth A

2003-01-01

Desert tortoise (Gopherus agassizii) populations have experienced precipitous declines resulting from the cumulative impact of habitat loss and human and disease-related mortality. Diagnosis of disease in live, free-ranging tortoises is facilitated by evaluation of clinical signs and laboratory test results but may be complicated by seasonal and environmental effects. The goals of this study were: 1) to describe and monitor clinical and laboratory signs of disease in adult, free-ranging desert tortoises at three sites in the Mojave Desert of California (USA) between October 1990 and October 1995; 2) to evaluate associations between clinical signs and hematologic, biochemical, serologic, and microbiologic test results; 3) to characterize disease patterns by site, season, and sex; and 4) to assess the utility of diagnostic tests in predicting morbidity and mortality. Venous blood samples were obtained four times per year from tortoises of both sexes at the Desert Tortoise Research Natural Area (DTNA), Goffs/Fenner Valley, and Ivanpah Valley. Tortoises were given a physical examination, and clinical abnormalities were graded by type and severity. Of 108 tortoises, 68.5% had clinical signs of upper respiratory tract disease consistent with mycoplasmosis at least once during the study period. In addition, 48.1% developed moderate to severe shell lesions consistent with cutaneous dyskeratosis. Ulcerated or plaque-like oral lesions were noted on single occasions in 23% of tortoises at Goffs and 6% of tortoises at Ivanpah. Tortoises with oral lesions were significantly more likely than tortoises without lesions to have positive nasal cultures for Mycoplasma agassizii (P = 0.001) and to be dehydrated (P = 0.0007). Nine tortoises had marked azotemia (blood urea nitrogen [BUN] > 100 mg/dl) or persistent azotemia (BUN 63-76 mg/dl); four of these died, three of which had necropsy confirmation of urinary tract disease. Laboratory tests had low sensitivity but high specificity in

Clinical disease and laboratory abnormalities in free-ranging desert tortoises in California (1990-1995)

USGS Publications Warehouse

Christopher, Mary M.; Berry, Kristin H.; Henen, Brian T.; Nagy, Kenneth A.

2003-01-01

Desert tortoise (Gopherus agassizii) populations have experienced precipitous declines resulting from the cumulative impact of habitat loss and human and disease-related mortality. Diagnosis of disease in live, free-ranging tortoises is facilitated by evaluation of clinical signs and laboratory test results but may be complicated by seasonal and environmental effects. The goals of this study were: 1) to describe and monitor clinical and laboratory signs of disease in adult, free-ranging desert tortoises at three sites in the Mojave Desert of California (USA) between October 1990 and October 1995; 2) to evaluate associations between clinical signs and hematologic, biochemical, serologic, and microbiologic test results; 3) to characterize disease patterns by site, season, and sex; and 4) to assess the utility of diagnostic tests in predicting morbidity and mortality. Venous blood samples were obtained four times per year from tortoises of both sexes at the Desert Tortoise Research Natural Area (DTNA), Goffs/Fenner Valley, and Ivanpah Valley. Tortoises were given a physical examination, and clinical abnormalities were graded by type and severity. Of 108 tortoises, 68.5% had clinical signs of upper respiratory tract disease consistent with mycoplasmosis at least once during the study period. In addition, 48.1% developed moderate to severe shell lesions consistent with cutaneous dyskeratosis. Ulcerated or plaque-like oral lesions were noted on single occasions in 23% of tortoises at Goffs and 6% of tortoises at Ivanpah. Tortoises with oral lesions were significantly more likely than tortoises without lesions to have positive nasal cultures for Mycoplasma agassizii(P=0.001) and to be dehydrated (P=0.0007). Nine tortoises had marked azotemia (blood urea nitrogen [BUN] >100 mg/dl) or persistent azotemia (BUN 63–76 mg/dl); four of these died, three of which had necropsy confirmation of urinary tract disease. Laboratory tests had low sensitivity but high specificity in

Clinical features of Crohn disease concomitant with ankylosing spondylitis: A preliminary single-center study.

PubMed

Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian

2016-07-01

Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS.We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison.Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (-) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73-0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = -0.73 to -0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = -0.81 to -0.91, P < 0.05).Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected.

Treatments for Parkinson disease--past achievements and current clinical needs.

PubMed

Poewe, Werner

2009-02-17

Although idiopathic Parkinson disease (PD) remains the only neurodegenerative disorder for which there are highly effective symptomatic therapies, there are still major unmet needs regarding its long-term management. Although levodopa continues as the gold standard for efficacy, its chronic use is associated with potentially disabling motor complications. Current evidence suggests that these are related to mode of administration, whereby multiple oral doses of levodopa generate pulsatile stimulation of striatal dopamine receptors. Current dopamine agonists, while producing more constant plasma levels, fail to match levodopa's efficacy. Strategies to treat levodopa-related motor complications are only partially effective, rarely abolishing motor fluctuations or dyskinesias. Best results are currently achieved with invasive strategies via subcutaneous (s.c.) or intraduodenal delivery of apomorphine or levodopa, or deep brain stimulation of the subthalamic nucleus. Another area of major unmet medical need is related to nondopaminergic and nonmotor symptoms of PD. Targeting transmitter systems beyond the dopamine system is an interesting approach, both for the motor and nonmotor problems of PD. So far, clinical trial evidence regarding 5-HT agonists, glutamate antagonists, adenosine A(2) antagonists and alpha-adrenergic receptor antagonists, has been inconsistent, but trials with cholinesterase inhibitors and atypical antipsychotics to treat dementia and psychosis, have been successful. However, the ultimate goal of PD medical management is modifying disease progression, thereby delaying the evolution of motor and nonmotor complications of advanced disease. As understanding of preclinical markers for PD develops, there is new hope for neuropreventive strategies to target "at risk" populations before clinical onset of disease.

AB022. Harnessing big data to transform clinical care of cardiovascular diseases

PubMed Central

Cutiongco-de la Paz, Eva Maria

2015-01-01

Diseases of the heart and vascular system are the leading causes of mortality worldwide. A number of risk factors have already been identified such as obesity, diabetes and smoking; in the recent years, research has shifted its focus on genetic risk factors. Discoveries on the role of genes partnered with the technological developments have enabled advances in the understanding of human genetics and its influence on disease and treatment. There are initiatives now to combine medical records and genetic and other molecular data into a single “knowledge network” to achieve these aptly known as precision medicine. With next generation sequencing readily available at a more affordable cost, it is expected that genetic information of patients will be increasingly available and can be used to guide clinical decisions. Big data generated and stored necessitates broad and extensive interpretation to be valuable in clinical care. Accumulating evidence on the use of such genetic information in the cardiovascular clinics will be presented.

From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics.

PubMed

Trigueros Genao, M; Torres, R J

2014-11-01

Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease.

PubMed

Mehta, Seema; Lopez, Monica E; Chumpitazi, Bruno P; Mazziotti, Mark V; Brandt, Mary L; Fishman, Douglas S

2012-01-01

Our center previously reported its experience with pediatric gallbladder disease and cholecystectomies from 1980 to 1996. We aimed to determine the current clinical characteristics and risk factors for symptomatic pediatric gallbladder disease and cholecystectomies and compare these findings with our historical series. Retrospective, cross-sectional study of children, 0 to 18 years of age, who underwent a cholecystectomy from January 2005 to October 2008. We evaluated 404 patients: 73% girls; 39% Hispanic and 35% white. The mean age was 13.10 ± 0.91 years. The primary indications for surgery in patients 3 years or older were symptomatic cholelithiasis (53%), obstructive disease (28%), and biliary dyskinesia (16%). The median BMI percentile was 89%; 39% were classified as obese. Of the patients with nonhemolytic gallstone disease, 35% were obese and 18% were severely obese; BMI percentile was 99% or higher. Gallstone disease was associated with hemolytic disease in 23% (73/324) of patients and with obesity in 39% (126/324). Logistic regression demonstrated older age (P = .019) and Hispanic ethnicity (P < .0001) as independent risk factors for nonhemolytic gallstone disease. Compared with our historical series, children undergoing cholecystectomy are more likely to be Hispanic (P = .003) and severely obese (P < .0279). Obesity and Hispanic ethnicity are strongly correlated with symptomatic pediatric gallbladder disease. In comparison with our historical series, hemolytic disease is no longer the predominant risk factor for symptomatic gallstone disease in children.

Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

PubMed

Savige, Judy; Dagher, Hayat; Povey, Sue

2014-07-01

This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

Cytomegalovirus disease in kidney transplant recipients: incidence, clinical profile, and risk factors.

PubMed

Cordero, E; Casasola, C; Ecarma, R; Danguilan, R

2012-04-01

Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation. Approximately 60% of transplant recipients will have CMV infection and >20% will develop symptomatic disease. With the advancement of immunosuppression, variation in the occurrence and pattern of infections is possible. We described the incidence, clinical profile, outcome, and risk factors for development of CMV disease among renal transplant recipients. We studied patients who underwent transplantation from January 2005-December 2009 admitted for CMV disease. CMV infection was present if the patient had at least 1 of the following: positive early antigen detection in blood or tissues, positive CMV antigenemia, or a 4-fold increase in pretransplantation CMV antibody titer. CMV disease was diagnosed if CMV infection was accompanied by clinical signs and symptoms. Descriptive statistics included measures of central tendency for continuous numerical variables and percentage-frequency distribution for categorical variables z test, Wilcoxon-Mann-Whitney test, and Fisher exact test were used to determine risk factors for CMV disease. About 1502 renal transplantations were done during the study period with mean follow-up of 33.8 months. CMV disease was confirmed in 85 (5.8%) recipients who developed 88 CMV disease episodes. Of the 85 patients who had CMV disease, 55% developed ≤ 3 months posttransplantation. Fever was the most common presenting symptom, 53% had coinfection, and case fatality rate was 11%. Risk factors that were statistically significant in the development of CMV disease were as follows: recipient/donor relationship (P = .0115), CMV donor+/recipient- (P = .004), and recent rejection treatment (P = .0084). Incidence of CMV disease was 5.8% with fever as the most common presenting symptom and 55% developed CMV disease ≤ 3 months posttransplantation. Coinfection occurred in 53% and case fatality rate in 11%. Risk factors for developing

Intracranial imaging of uncommon diseases is more frequently reported in clinical publications than in radiology publications.

PubMed

Lehman, V T; Doolittle, D A; Hunt, C H; Eckel, L J; Black, D F; Schwartz, K M; Diehn, F E

2014-01-01

Descriptions of uncommon diseases with intracranial imaging abnormalities are often difficult to find in the radiology literature. We hypothesized that reported imaging findings of such conditions in the recent literature were more frequent in clinical compared with radiology journals. PubMed searches from December 1, 2007 to December 1, 2012 were performed for 5 uncommon CNS diseases with intracranial imaging manifestations: 1) Susac syndrome; 2) amyloid β-related angiitis; 3) Parry-Romberg syndrome/en coup de sabre; 4) transient lesion of the splenium of the corpus callosum; and 5) reversible cerebral vasoconstriction syndrome. Articles were classified as a case report, case series, or original research. Journals were categorized as radiology or clinical. The 1- and 5-year Impact Factors of the journals were recorded. Two hundred two articles were identified for the 5 diseases, including 151 (74%) case reports, 26 case series (13%), and 25 original research articles (13%); 179 (89%) were published in nonradiology journals, compared with 23 (11%) in radiology journals. There was no significant difference between the mean 1- and 5-year Impact Factors of the radiology and clinical journals. Recent reports of the selected uncommon diseases with intracranial manifestations are more frequent in clinical journals when compared with dedicated radiology publications. Most publications are case reports. Radiologists should review both radiology and clinical journals when reviewing imaging features of uncommon diseases affecting the brain. Lack of reporting on such disease in the radiology literature may have significant practice, educational, and research implications for the radiology community.