Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha.

PubMed

Handschin, Christoph; Lin, Jiandie; Rhee, James; Peyer, Anne-Kathrin; Chin, Sherry; Wu, Pei-Hsuan; Meyer, Urs A; Spiegelman, Bruce M

2005-08-26

Inducible hepatic porphyrias are inherited genetic disorders of enzymes of heme biosynthesis. The main clinical manifestations are acute attacks of neuropsychiatric symptoms frequently precipitated by drugs, hormones, or fasting, associated with increased urinary excretion of delta-aminolevulinic acid (ALA). Acute attacks are treated by heme infusion and glucose administration, but the mechanisms underlying the precipitating effects of fasting and the beneficial effects of glucose are unknown. We show that the rate-limiting enzyme in hepatic heme biosynthesis, 5-aminolevulinate synthase (ALAS-1), is regulated by the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha). Elevation of PGC-1alpha in mice via adenoviral vectors increases the levels of heme precursors in vivo as observed in acute attacks. The induction of ALAS-1 by fasting is lost in liver-specific PGC-1alpha knockout animals, as is the ability of porphyrogenic drugs to dysregulate heme biosynthesis. These data show that PGC-1alpha links nutritional status to heme biosynthesis and acute hepatic porphyria.

Homozygous variegate porphyria presenting with developmental and language delay in childhood.

PubMed

Pinder, V A E; Holden, S T; Deshpande, C; Siddiqui, A; Mellerio, J E; Wraige, E; Powell, A M

2013-10-01

Variegate porphyria is an autosomal dominant disorder that usually presents with photosensitivity and acute neurological crises in adulthood. It is caused by heterozygous mutations in the protoporphyrinogen oxidase gene (PPOX). A rarer variant, homozygous variegate porphyria (HVP), presents in childhood with recurrent skin blisters and scarring. More variable features of HVP are short stature, brachydactyly, nystagmus, epilepsy, developmental delay and mental retardation. We describe a child who presented with nystagmus, developmental delay and ataxia, combined with a photosensitive eruption. Analysis of porphyrins in plasma, urine and stool supported a clinical diagnosis of HVP. DNA from the patient showed that he is compound heterozygous for two novel missense mutations in the PPOX coding region: c.169G>C (p.Gly57Arg) and c.1259C>G (Pro420Arg). Interestingly, cranial magnetic resonance imaging showed an absence of myelin, a feature not previously reported in HVP, which expands the differential diagnosis of childhood hypomyelinating leucoencephalopathies. © 2013 British Association of Dermatologists.

An Audit of the Use of Gonadorelin Analogues to Prevent Recurrent Acute Symptoms in Patients with Acute Porphyria in the United Kingdom.

PubMed

Schulenburg-Brand, Danja; Gardiner, Tricia; Guppy, Simon; Rees, David C; Stein, Penelope; Barth, Julian; Felicity Stewart, M; Badminton, Michael

2017-01-01

Severe recurrent acute attacks of porphyria have traditionally been treated with either prophylactic human haemin or gonadorelin analogues (GnA) in females. Evidence on the most effective treatment for this patient subgroup is lacking. This audit surveyed the use of prophylactic GnA in the UK.Twenty female patients (who experienced between 2 and 45 acute attacks of porphyria requiring hospitalisation and treatment with human haemin prior to GnA prophylaxis) were included in the audit. Data was retrospectively collected based on patient history and case review.Twenty three treatment courses were given lasting a median period of 12 months. Monthly subcutaneous Goserelin was most commonly used. In three patients in whom timing with the menstrual cycle was not considered, an acute attack occurred after initiation of the first dose. The majority of patients experienced oestrogen deficiency symptoms during treatment. Fifty percent of the prescribed courses of GnA resulted in a degree of clinical benefit. This successfully treated group experienced between 3 and 20 acute attacks prior to and between 0 and 6 acute attacks during GnA treatment.The audit revealed large variation in practice in the United Kingdom regarding indication, duration of treatment, specific drug used and management of side effects. In view of the limited treatment options available for this cohort and the mixed outcome successes reported, we believe it is reasonable for porphyria specialists to continue offering GnA treatment to women with severe recurrent debilitating acute attacks of porphyria associated with the menstrual cycle, and we propose best practice guidelines to standardise management.

Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients*

PubMed Central

Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; dos Reis, Vitor Manoel Silva

2013-01-01

BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients PMID:24068123

The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6

PubMed Central

Fukuda, Yu; Cheong, Pak Leng; Lynch, John; Brighton, Cheryl; Frase, Sharon; Kargas, Vasileios; Rampersaud, Evadnie; Wang, Yao; Sankaran, Vijay G.; Yu, Bing; Ney, Paul A.; Weiss, Mitchell J.; Vogel, Peter; Bond, Peter J.; Ford, Robert C.; Trent, Ronald J.; Schuetz, John D.

2016-01-01

Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins. Functional studies show that most of these ABCB6 variants are expressed poorly and/or have impaired function. Accordingly, homozygous disruption of the Abcb6 gene in mice exacerbates porphyria phenotypes in the Fechm1Pas mouse model, as evidenced by increased porphyrin accumulation, and marked liver injury. Collectively, these studies support ABCB6 role as a genetic modifier of porphyria and suggest that porphyrin-inducing drugs may produce excessive toxicities in individuals with the rare Lan(−) blood type. PMID:27507172

An update of clinical management of acute intermittent porphyria

PubMed Central

Pischik, Elena; Kauppinen, Raili

2015-01-01

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. PMID:26366103

Porphyria cutanea tarda and haemochromatosis: a family study.

PubMed Central

Seymour, D G; Elder, G H; Fryer, A; Jacobs, A; Williams, G T

1990-01-01

A female patient aged 73 presented with a history of general malaise and hyperpigmentation. Iron studies in the patient and immediate family members indicated that the proband was homozygous for haemochromatosis, but subsequent investigations revealed that porphyria cutanea tarda was responsible for her signs and symptoms. Venesection of four units of blood brought her symptoms under control. The interplay between porphyria cutanea tarda and excess iron deposition is discussed as is the role of extending investigations to first and second degree relatives when either haemochromatosis or porphyria cutanea tarda is suspected. PMID:2379879

Hepatoerythropoietic porphyria precipitated by viral hepatitis.

PubMed Central

Hift, R J; Meissner, P N; Todd, G

1993-01-01

Porphyria cutanea tarda (PCT), the condition resulting from a deficiency of hepatic uroporphyrinogen decarboxylase activity, is the commonest form of porphyria. Both acquired and familial form exist and are commonly associated in adults with liver disease and hepatic iron overload. The condition is extremely rare in children; most cases of childhood PCT are familial and some particularly severe cases have been shown to have a hepatoerythropoietic porphyria or homozygous uroporphyrinogen decarboxylase deficiency. A case is described of hepatoerythropoietic porphyria in which the disease was first precipitated at the age of two by a coincidental hepatitis A infection and improved as the hepatitis cleared. This paper reviews the evidence that viral hepatitis may precipitate overt PCT in children in a manner analogous to the precipitation of PCT in adults by alcohol associated liver disease. PMID:7902313

Successful and safe treatment of hypertrichosis by high-intensity pulses of noncoherent light in a patient with hepatoerythropoietic porphyria.

PubMed

García-Bravo, María; López-Gómez, Sara; Segurado-Rodríguez, María-Agustina; Morán-Jiménez, María-José; Méndez, Manuel; de Salamanca, Rafael Enríquez; Fontanellas, Antonio

2004-08-01

Hypertrichosis is a common feature in cutaneous porphyrias, characterized by high accumulation of photoreactive porphyrins. Photothermolysis induced by noncoherent light (755-1200 nm) and energy fluence of 42 J/cm(2) was applied to a patient with hepatoerythropoietic porphyria. Hypertrichosis was almost completely removed after seven sessions without development of skin lesions.

PBG urine test

MedlinePlus

... test. Alternative Names Porphobilinogen test; Porphyria - urine; PBG Images Male urinary system References Fuller SJ, Wiley JS. Heme biosynthesis and its disorders: porphyrias and sideroblastic ...

Markers for vulnerability in acute porphyria. A hypothesis paper.

PubMed

Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

1995-04-01

Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin concentration. This may mirror a role of the cobalamin-folate system in the acute porphyric process.

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed Central

Stine, O C; Smith, K D

1990-01-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive. PMID:2137963

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed

Stine, O C; Smith, K D

1990-03-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive.

Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families.

PubMed

Kotze, M J; De Villiers, J N; Groenewald, J Z; Rooney, R N; Loubser, O; Thiart, R; Oosthuizen, C J; van Niekerk, M M; Groenewald, I M; Retief, A E; Warnich, L

1998-10-01

A subset of probands from 11 South African families with clinical and/or biochemical features of variegate porphyria (VP), but without the known protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South African population, were subjected to mutation analysis. Disease-related mutation(s) could not be identified after screening virtually the entire PPOX gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP), although three new sequence variants were detected in exon 1 of the gene in three normal controls. The presence of these single base changes at nucleotide positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1 polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX gene is particularly mutation-prone. Furthermore, microsatellite markers flanking the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14, respectively, were used to assess the probability of involvement of these loci in disease presentation. Common alleles transmitted from affected parent to affected child were determined where possible in the mutation-negative index cases. Allelic frequencies of these alleles were compared to findings in the normal population, but no predominant disease-associated allele could be identified. Co-segregation of a specific haplotype with the disease phenotype could also not be demonstrated in a large Afrikaner family. It is concluded that further studies are warranted to determine the genetic factor(s) underlying the autosomal dominant pattern of inheritance in molecularly uncharacterized cases showing clinical symptoms of an acute porphyria. Copyright 1998 Academic Press.

Porphyria: A Suitable Case for Teaching.

ERIC Educational Resources Information Center

Hawkey, Roy

1990-01-01

The porphyrias are a family of genetic disorders whose genetics and biochemistry are largely identified. Background information on these diseases are discussed including porphyrins, gene expression, population genetics, and historical significance. (CW)

Porphyrins and Porphyria Diagnosis

MedlinePlus

... diagnosis The porphyrias are caused by deficiencies of enzymes of the heme biosynthetic pathway. This pathway, like ... heme. Heme is essential for life, and each enzyme is also essential, because it is responsible for ...

American Porphyria Foundation

MedlinePlus

... helping us all connect with each other." ~ Amy Rose Burke, PCT “APF is not only a support ... Darnisha Davenport Liz Cooke Nicole Clarke Louise Coomber Rose and Colin ~ Living with Porphyria ~ Video Jessi Brill ...

Diet and Nutrition in Porphyria

MedlinePlus

... the APF You are here Home Diet and Nutrition A proper diet is important to all individuals, ... alter food intake. Therefore, attention to diet and nutrition is important in almost any disease. Porphyrias are ...

Porphyrin Test: MedlinePlus Lab Test Information

MedlinePlus

... cause skin symptoms when you are exposed to sunlight Some porphyrias affect both the nervous system and ... Hallucinations Symptoms of cutaneous porphyria include: Oversensitivity to sunlight Blisters on skin exposed to sunlight Redness and ...

Weight Loss & Acute Porphyria

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Porphyria Treatment Options

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.

PubMed

Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

2016-05-31

Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias - decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis.

Glucose Effect in the Acute Porphyrias

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Porphyria

MedlinePlus

... Hift RJ. The porphyrias. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 210. Review Date 2/1/2017 Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Pearls and pitfalls in the horror cinema.

PubMed

Pascuzzi, R M

1998-01-01

Observations on the neurologic signs and symptoms of Count Dracula, Wolfman, and Frankenstein's Monster are presented as viewed by a specialist in neuromuscular disease. Key clinical features of these horror movie figures illustrate a variety of pearls in the diagnosis of a variety of neurologic disorders, including porphyria, lead poisoning, osteosclerotic myeloma, and myasthenia gravis.

Congenital erythropoietic porphyria in an African hedgehog (Atelerix albiventris).

PubMed

Wolff, Carlos; Corradini, Paulina; Cortés, Galaxia

2005-06-01

A 6-mo-old, male African hedgehog (Atelerix albiventris) presented with a history of pink urine and demonstrating pink-colored teeth and mild hepatomegaly on examination. Urinalysis revealed no physical, chemical, or cellular abnormalities other than a pink color and fluorescence under ultraviolet light (UV). Also under UV, intense fluorescence of teeth, feet, and spines was noted. Porphyria was suspected. Spectrophotometric evaluation of urine showed extremely elevated levels of copro- and uroporphyrins. Analysis of the urine by thin-layer chromatography showed an abnormal pattern of excreted porphyrin intermediates. Urine high-performance thin-layer chromatography showed that excreted porphyrins were 90-95% of the type-I isomeric form, suggestive of congenital erythropoietic porphyria.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2010 CFR

2010-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2013 CFR

2013-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2011 CFR

2011-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2012 CFR

2012-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2014 CFR

2014-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

Successful cord blood stem cell transplantation for congenital erythropoietic porphyria (Gunther's disease).

PubMed

Zix-Kieffer, I; Langer, B; Eyer, D; Acar, G; Racadot, E; Schlaeder, G; Oberlin, F; Lutz, P

1996-07-01

Congenital erythropoietic porphyria (Gunther's disease, GD) is a rare autosomal recessive disease. It results from the deficiency of uroporphyrinogen III synthase, the fourth enzyme on the metabolic pathway of heme synthesis. GD leads to severe scarring of the face and hands as a result of photosensitivity and fragility of the skin due to uroporphyrin I and coproporphyrin I accumulation. It also causes erythrocyte fragility leading to haemolytic anaemia. The other clinical features include hirsutism, red discolouration of teeth, finger-nails and urine and stunted growth. The outcome is poor, and the disfiguring nature of GD may partly explain the legend of the werewolf. No curative treatment was known until 1991, when the first case of BMT in GD was reported. The clinical and biological outcome after transplantation was encouraging, with an important regression of the symptoms of the disease, but the child died of CMV-infection 11 months after BMT. We report the second case of GD treated successfully by stem cell transplantation using umbilical cord blood from an HLA-identical brother in a 4-year-old girl suffering from severe GD. Our patient is very well 10 months after transplantation. We confirm that stem cell transplantation is curative for GD.

Characterization of variegate porphyria mutations using a minigene approach.

PubMed

Granata, Barbara Xoana; Baralle, Marco; De Conti, Laura; Parera, Victoria; Rossetti, Maria Victoria

2015-01-01

Porphyrias are a group of metabolic diseases that affect the skin and/or nervous system. In 2008, three unrelated patients were diagnosed with variegate porphyria at the CIPYP (Centro de Investigaciones sobre Porfirinas y Porfirias). Sequencing of the protoporphyrinogen oxidase gene, the gene altered in this type of porphyria, revealed three previously undescribed mutations: c.338+3insT, c.807G>A, and c.808-1G>C. As these mutations do not affect the protein sequence, we hypothesized that they might be splicing mutations. RT-PCRs performed on the patient's mRNAs showed normal mRNA or no amplification at all. This result indicated that the aberrant spliced transcript is possibly being degraded. In order to establish whether they were responsible or not for the patient's disease by causing aberrant splicing, we utilized a minigene approach. We found that the three mutations lead to exon skipping; therefore, the abnormal mRNAs are most likely degraded by a mechanism such as nonsense-mediated decay. In conclusion, these mutations are responsible for the disease because they alter the normal splicing pathway, thus providing a functional explanation for the appearance of disease and highlighting the use of minigene assays to complement transcript analysis.

Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.

PubMed Central

Giddens, W. E.; Labbe, R. F.; Swango, L. J.; Padgett, G. A.

1975-01-01

A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:1231563

Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs.

PubMed

Krijt, J; Stranska, P; Maruna, P; Vokurka, M; Sanitrak, J

1997-01-01

Administration of oxadiazon or oxyfluorfen (1000 ppm in the diet) to male BALB/c mice for 9 days resulted in experimental porphyria, resembling the acute phase of human variegate porphyria. Urinary concentrations of 5-aminolevulinic acid and porphobilinogen reached 1500 and 3000 mumol/L, respectively. Both herbicides caused a decrease of protoporphyrinogen oxidase activity in liver and kidney. Brain protoporphyrinogen oxidase activity was not altered. Liver and kidney porphyrin content increased to 11 and 17 nmol/g, respectively (control mice, 2 nmol/g). Over 50% of liver and kidney porphyrins were in the reduced (porphyrinogen) form. Bile of oxadiazon-treated mice contained 700 nmol/mL of protoporphyrinogen (control mice, 15 nmol/mL). Porphyrin content of the trigeminal nerve increased from 1 nmol/g in control animals to 11 nmol/g in oxadiazon-treated animals, suggesting a possible contribution of peripheral nerve porphyrins to porphyric neuropathy. Mice treated with 125 ppm of oxadiazon in the diet for 9 days excreted moderately elevated levels of porphobilinogen in urine (control mice, less than 50 mumol/L; treated mice, 330 mumol/L). Administration of phenobarbital or phenytoin (single injections on days 7, 8, and 9) increased the urinary porphobilinogen concentration to 3500 mumol/L. This response to porphyrogenic drugs resembles the response observed in human acute porphyrias.

Acute intermittent porphyria in Argentina: an update.

PubMed

Cerbino, Gabriela Nora; Gerez, Esther Noemí; Varela, Laura Sabina; Melito, Viviana Alicia; Parera, Victoria Estela; Batlle, Alcira; Rossetti, María Victoria

2015-01-01

Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in hydroxymethylbilane synthase (HMBS) produces a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP). Thirty-five different mutations were found, of which 14 were described for the first time in our population. The most prevalent type of mutations was the missense mutations (43%) followed by splice defects (26%) and small deletions (20%). An odd case of a double heterozygous presentation of AIP in a foreign family from Paraguay is discussed. Moreover, it can be noted that 38 new families were found carrying the most frequent mutation in Argentina (p.G111R), increasing to 55.66% the prevalence of this genetic change in our population and adding further support to our previous hypothesis of a founder effect for this mutation in Argentina. Identification of patients with an overt AIP is important because treatment depends on an accurate diagnosis, but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm.

PubMed

Luck, Margaux; Schmitt, Caroline; Talbi, Neila; Gouya, Laurent; Caradeuc, Cédric; Puy, Hervé; Bertho, Gildas; Pallet, Nicolas

2018-01-01

Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Urine 1 H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.

Activation of the complement system in patients with porphyrias after irradiation in vivo.

PubMed Central

Lim, H W; Poh-Fitzpatrick, M B; Gigli, I

1984-01-01

Irradiation of the forearms of two patients with erythropoietic protoporphyria and one patient with porphyria cutanea tarda resulted in an in vivo activation of the complement system, as assessed by diminution of the hemolytic titers of the third component of complement by 23-57%, and of the fifth component of complement (C5) by 19-47%. Such treatment also generated chemotactic activity for human polymorphonuclear cells; the chemotactic activity was stable at 56 degrees C and antigenically related to human C5. On Sephadex G-75 chromatography the chemotactic activity eluted with an apparent molecular weight of 15,000. These in vivo results extend our previous in vitro observation of photoactivation of complement in sera from patients with erythropoietic protoporphyria and porphyria cutanea tarda, and suggest that the complement system may participate in the pathogenesis of cutaneous phototoxicity in these patients. PMID:6392339

Uroporphyrin I Stimulation of Collagen Biosynthesis in Human Skin Fibroblasts

PubMed Central

Varigos, George; Schiltz, John R.; Bickers, David R.

1982-01-01

Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [3H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5- to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities). No changes in morphology of the treated cells occurred. These studies indicate that porphyrins possess previously undemonstrated biological effects that are independent of their photosensitizing properties. This novel dark effect of uroporphyrin I may account for the sclerodermatous lesions seen in the skin of patients with porphyria cutanea tarda and erythropoietic porphyria. PMID:7054234

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene

PubMed Central

To-Figueras, J.; Phillips, J.; Gonzalez-López, J.M.; Badenas, C.; Madrigal, I.; González-Romarís, E.M.; Ramos, C.; Aguirre, J.M.; Herrero, C.

2013-01-01

Summary Background Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria that results from a deficiency of uroporphyrinogen decarboxylase (UROD). The disease is caused by homoallelism or heteroallelism for mutations in the UROD gene. Objective To study a 19 year-old woman from Equatorial Guinea, one of the few cases of HEP of African descent and to characterize a new mutation causing HEP. Methods Excretion of porphyrins and residual UROD activity in erythrocytes were measured and compared to other HEP patients. UROD gene of the proband was sequenced and a new mutation identified. The recombinant UROD protein was purified and assayed for enzymatic activity. The aminoacid change mapped to the UROD protein and the functional consequences were predicted. Results The patient presented a novel G170D missense mutation in homozygosity. Porphyrin excretion showed an atypical pattern in stool with a high pentaporphyrin III to isocoproporphyrin ratio. Erythrocyte UROD activity was 42 % of normal and higher than the activity found in HEP patients with a G281E mutation. The recombinant UROD protein showed a relative activity of 17 % and 60 % of wild-type towards uroporphyrinogen I and III respectively. Molecular modelling showed that glycine 170 is located on the dimer interface of UROD, in a loop containing residues 167-172 that are critical for optimal enzymatic activity and that carboxyl side chain from aspartic acid is predicted to cause negative interactions between the protein and the substrate. Conclusions The results emphasize the complex relationship between the genetic defects and the biochemical phenotype in homozygous porphyria. PMID:21668429

May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population.

PubMed

Hrdinka, M; Puy, H; Martasek, P

2006-01-01

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis caused by molecular defects in the porphobilinogen deaminase (PBGD) gene. This paper reviews published mutations, their types, and polymorphisms within the PBGD gene. To date, 301 different mutations and 21 polymorphisms have been identified in the PBGD gene in AIP patients and individuals from various countries and ethnic groups. During the search for mutations identified among Slavic AIP patients we found 65 such mutations and concluded that there is not a distinct predominance of certain mutations in Slavs.

Porphyria

MedlinePlus

... Process Research Training & Career Development Funded Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

PubMed Central

Sassa, S; Zalar, G L; Poh-Fitzpatrick, M B; Anderson, K E; Kappas, A

1982-01-01

In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP accumulate approximately twice as much protoporphyrin IX as cells from normal subjects when incubated with a porphyrin precursor, gamma-aminolevulinic acid (ALA). Treatment of cultures with ALA and with the iron chelator, CaMgEDTA significantly increased the level of protoporphyrin IX in mitogen-stimulated lymphocytes from normal subjects, while the same treatment failed to produce an increase in protoporphyrin IX in cell preparations from EPP patients. In contrast to the results with the chelator treatment, supplementation of the cultures with iron and ALA reduced the level of protoporphyrin IX in normal cells, but not in EPP cells. These findings are compatible with a partial deficiency of ferrochelatase in EPP lymphocytes. The gene defects of acute intermittent porphyria and hereditary coproporphyria have previously been identified using lymphocyte preparations from the gene carriers of these diseases. The present study demonstrates that EPP represents another form of human porphyria in which the gene defect of the disease can now be identified in lymphocyte preparations. PMID:6804493

Porphyria

MedlinePlus

... numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms come and go. Certain triggers can cause an attack, including some medicines, smoking, drinking alcohol, ...

Hematin and propranolol in acute intermittent porphyria. Full recovery from quadriplegic coma and respiratory failure.

PubMed

Brezis, M; Ghanem, J; Weiler-Ravell, D; Epstein, O; Morris, D

1979-01-01

The authors present a case of acute intermittent porphyria (AIP) in an almost fatal relapse with quadriplegia, bulbar paralysis and coma. Intravenous hematin produced an immediate arousal from coma and allowed a gradual resumption of bulbar and autonomic functions. Persistent tachycardia and hypertension necessitated huge doses of intravenous propranolol. Both hematin and propranolol administrations were followed by a remarkable decrease in urinary amino-levulinic acid and porphobilinogen excretion. Nevertheless, after the acute stage, the patient was left with a severe generalized muscle wasting. After 7 months of intensive physical therapy, complete recovery of all neuromuscular functions was achieved. The modern aspects of the management of AIP are presented; the efficacy and the limits of hematin and propranolol therapy are discussed.

Nuclear microscopy in biomedical analysis with special emphasis on clinical metal biology

NASA Astrophysics Data System (ADS)

Lindh, Ulf; Frisk, Peter; Nyström, Joakim; Danersund, Antero; Hudecek, Romuald; Lindvall, Anders; Thunell, Stig

1997-07-01

Nuclear microscopy based upon developments in high energy ion beam techniques is by now an accepted technique in many fields of research. The advancements into the biomedical field have, however, been slower than expected. A major factor explaining this tendency is the availability of nuclear microscopy. This paper reviews briefly the biomedical work using nuclear microscopy that has been carried out since the 4 th International Conference on Nuclear Microprobe Technology and Applications held in Shanghai. Nuclear microscopy of isolated individual blood cells from patients adversely affected by metal exposure from dental amalgam has been performed both before and after removal of the metallic fillings. The elemental profile of blood cells was more or less normalised after treatment. Some of these results will be presented to illustrate a medical application. Results from bulk analysis by ICP-MS of erythrocytes and plasma before and after treatment will also be presented to illustrate the difference in information content between these two approaches as well as the need for complementary information in solving biomedical problems. As part of a larger study of acute porphyria, nuclear microscopy of blood cells was included among the 78 laboratory tests. The approach in this study was unbiased in the sense that no hypothesis was formulated as to which laboratory parameters would be the most explanatory for health or disease. Multivariate discriminant analysis was applied to the large amounts of data acquired. This approach led to the hypothesis that oxidative stress increased the synthesis of manganese-dependent superoxide dismutase in the mitochondria of polymorphonuclear leukocytes, explaining the increase of manganese in these cells. Antioxidant therapy was therefore applied to a couple of patients with porphyria, however, without clinical success.

Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda.

PubMed

Stölzel, Ulrich; Köstler, Erich; Schuppan, Detlef; Richter, Matthias; Wollina, Uwe; Doss, Manfred O; Wittekind, Christian; Tannapfel, Andrea

2003-03-01

To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. Academic teaching hospital. For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.

Porphyrins - urine test

MedlinePlus

Urine uroporphyrin; Urine coproporphyrin; Porphyria - uroporphyrin ... After you provide a urine sample, it is tested in the lab. This is called a random urine sample. If needed, your health care provider ...

Co-trimoxazole

MedlinePlus

... cannot digest the nutrients needed for good health); human immunodeficiency virus (HIV) infection; porphyria (an inherited blood disease that may cause skin or nervous system problems); thyroid disease; or glucose-6-phosphate dehydrogenase ( ...

Griseofulvin

MedlinePlus

... ever had liver disease, porphyria, lupus, or a history of alcohol abuse.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking griseofulvin, call ...

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

PubMed Central

Fujita, H; Sassa, S; Toback, A C; Kappas, A

1987-01-01

Hepatoerythropoietic porphyria (HEP) is due to a marked deficiency of uroporphyrinogen (URO) decarboxylase, a cytosolic enzyme in the heme biosynthetic pathway. Using a radioimmunoassay method, we determined the concentration of URO decarboxylase protein in erythrocytes from a patient with mild HEP and found that the enzyme protein concentration had markedly decreased to less than 7% of the normal controls. This finding, however, was in contrast to the enzyme activity in the patient's erythrocytes, which was 16% of normal control levels and different from previously reported HEP cases in that erythrocytes in our patient contained disproportionately elevated URO decarboxylase activity in comparison to its immunoreactive material. Our findings suggests the possibility of a mutant isozyme in this patient that is not immunoreactive with an antibody raised against the normal enzyme. PMID:3571497

Diagnosing the dead: the retrospective analysis of genetic diseases.

PubMed

Rushton, A R

2013-01-01

The suspected presence of hereditary disease in important historical and political figures has interested researchers for many decades. Whether Abraham Lincoln suffered from Marfan syndrome, if George III became 'mad' because he inherited variegate porphyria, and if the Romanov dynasty collapsed because the heir Alexei inherited haemophilia are important questions; physical illness can adversely affect the ability of leaders to function within the social and political realm of their day. This article will outline an approach to such a medical-historical analysis including assessment of hereditary predisposition, family history and the use of DNA technology to confirm or deny the clinical suspicions of the investigator.

Congenital Erythropoietic Porphyria (CEP)

MedlinePlus

... can be severe and such patients require periodic transformations to maintain sufficient red blood cells. In severely ... DAY FOR PATIENTS! date: Dec 9, 2017 PATIENT EDUCATION AND SUPPORT MEETING - ATLANTA » More upcoming events Athi ...

Porphyria Cutanea Tarda and Agent Orange

MedlinePlus

... of Medicine) of the National Academy of Sciences, Engineering, and Medicine concluded in its 1994 report on " ... VA Plans, Budget, & Performance VA Claims Representation RESOURCES Careers at VA Employment Center Returning Service Members Vocational ...

Meprobamate

MedlinePlus

... have ever had kidney or liver disease, a history of alcohol or drug abuse, porphyria, or epilepsy.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking meprobamate, call ...

Effective Gene Therapy of Mice with Congenital Erythropoietic Porphyria Is Facilitated by a Survival Advantage of Corrected Erythroid Cells

PubMed Central

Robert-Richard, Elodie; Moreau-Gaudry, François; Lalanne, Magalie; Lamrissi-Garcia, Isabelle; Cario-André, Muriel; Guyonnet-Dupérat, Véronique; Taine, Laurence; Ged, Cécile; de Verneuil, Hubert

2008-01-01

Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Urosmut248 mice resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate that the cure of this mouse model of CEP at a moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified hematopoietic stem cells. PMID:18179890

[Hereditary haemochromatosis].

PubMed

Bismuth, Michael; Aguilar-Martinez, Patricia; Michel, Henri

2003-11-08

EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common genetic disease in France. Its frequency is on average 1 out of 300 French individuals. It is due to excessive dietary iron absorption, leading to accumulation of iron in the body. Mutations of the HFE1 gene are responsible for the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The first clinical manifestations (weakness, sexual dysfunction, arthralgia, cardiac symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35 years in women (protected for longer by menstruation, pregnancy and delivery). In the absence of diagnosis, severe complications can develop during the 5th decade: nervous breakdown, arthropathy, heart failure, diabetes mellitus, cirrhosis with risk of progression towards carcinoma, responsible for handicaps and premature death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in transferrine saturation (>45%), associated or not with excessive ferritin plasma levels. It is confirmed by the genetic test, showing homozygotes for the C282Y mutation or compound heterozygotes for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies hepatic iron loading and generally avoids the need for a liver biopsy. The differential diagnosis must exclude secondary iron overload due to chronic transfusions in congenital or acquired blood diseases, a polymetabolic syndrome, chronic viral or alcoholic hepatic diseases and porphyria cutanea tarda. EFFICIENT TREATMENT: Today, haemochromatosis is still treated by phlebotomy. This consists in withdrawing 400 to 500ml of blood every week at the initial depletion stage and subsequently a maintenance therapy in order to maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance, hereditary haemochromatosis remains a serious disease, although its diagnosis is easy and the treatment simple and effective.

[Skin and chronic kidney disease].

PubMed

Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

2014-01-01

Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process.

Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review.

PubMed

Ferreli, Caterina; Gasparini, Giulia; Parodi, Aurora; Cozzani, Emanuele; Rongioletti, Franco; Atzori, Laura

2017-12-01

Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

Allosteric Inhibition of Human Porphobilinogen Synthase*

PubMed Central

Lawrence, Sarah H.; Ramirez, Ursula D.; Selwood, Trevor; Stith, Linda; Jaffe, Eileen K.

2009-01-01

Porphobilinogen synthase (PBGS) catalyzes the first common step in tetrapyrrole (e.g. heme, chlorophyll) biosynthesis. Human PBGS exists as an equilibrium of high activity octamers, low activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. It is posited that small molecules can be found that inhibit human PBGS activity by stabilizing the hexamer. Such molecules, if present in the environment, could potentiate disease states associated with reduced PBGS activity, such as lead poisoning and ALAD porphyria, the latter of which is associated with human PBGS variants whose quaternary structure equilibrium is shifted toward the hexamer (Jaffe, E. K., and Stith, L. (2007) Am. J. Hum. Genet. 80, 329–337). Hexamer-stabilizing inhibitors of human PBGS were identified using in silico prescreening (docking) of ∼111,000 structures to a hexamer-specific surface cavity of a human PBGS crystal structure. Seventy-seven compounds were evaluated in vitro; three provided 90–100% conversion of octamer to hexamer in a native PAGE mobility shift assay. Based on chemical purity, two (ML-3A9 and ML-3H2) were subjected to further evaluation of their effect on the quaternary structure equilibrium and enzymatic activity. Naturally occurring ALAD porphyria-associated human PBGS variants are shown to have an increased susceptibility to inhibition by both ML-3A9 and ML-3H2. ML-3H2 is a structural analog of amebicidal drugs, which have porphyria-like side effects. Data support the hypothesis that human PBGS hexamer stabilization may explain these side effects. The current work identifies allosteric ligands of human PBGS and, thus, identifies human PBGS as a medically relevant allosteric enzyme. PMID:19812033

Health hazard evaluation report HETA-83-297-1846, truck terminals, St. Louis, Missouri

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

McConnell, R.S.; Anderson, K.E.

1987-11-01

An evaluation was made of possible exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at trucking terminals in St. Louis, Missouri. A self-selected group of workers participated in a medical survey. A significant association was noted between symptoms of numbness in hands and feet, pins and needles in the extremities, insomnia and feelings of depression, and possible exposure to TCDD. One case of porphyria cutanea tarda and one of dermatofibrosarcoma were reported. The patient with porphyria cutanea tarda later developed a pelvic angiosarcoma. Environmental samples revealed a dioxin concentration of about 18.7 parts per billion on the rafters inside a terminal. Dioxin was presentmore » in two surface soil samples taken near an entrance gate. The authors conclude that no definite association between TCDD exposure and symptoms or medical problems can be established. The authors recommended that measures be taken to control or eliminate possible exposures at the terminals.« less

Differential effects of protoporphyrin and uroporphyrin on murine mast cells

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

Lim, H.W.; Gigli, I.; Wasserman, S.I.

1987-03-01

To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with (/sup 3/H)serotonin and (/sup 14/C)arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators ,f 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence ofmore » URO (50-5000 ng/ml) resulted in less than 5% net release. (3H)Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.« less

Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride

ClinicalTrials.gov

2017-10-12

Anti-Psychotic; Management of Manifestations of Psychotic Disorders; Treatment of Schizophrenia; Control Nausea and Vomiting; Relief of Restlessness and Apprehension Before Surgery; Acute Intermittent Porphyria; Adjunct in the Treatment of Tetanus; Control Manifestations of the Manic Type of Mani-depressive Illness; Relief of Intractable Hiccups

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

Effect of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen on liver uroporphyrin and heptacarboxylic porphyrin in two mouse strains.

PubMed

Krijt, J; Vokurka, M; Sanitrak, J; Janousek, V; van Holsteijn, I; Blaauboer, B J

1994-07-01

The effect of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen on liver porphyrin accumulation was studied in long-term high-dose experiments. Fomesafen caused liver accumulation of uroporphyrin and heptacarboxylic porphyrin when fed at 0.25% in the diet to male ICR mice for 5 months (fomesafen-treated mice: 52 nmol uroporphyrin, 21 nmol heptacarboxylic porphyrin/g liver; control mice: traces of uroporphyrin, heptacarboxylic porphyrin not detected). Uroporphyrinogen decarboxylase activity was depressed to about 25% of control values. Iron treatment accelerated the development of this porphyria cutanea tarda-like experimental porphyria both in ICR and C57B1/6J mice. In contrast to other uroporphyrinogen decarboxylase inhibitors, fomesafen treatment did not increase the cytochrome P450IA-related activities and the amount of P450IA2 protein was shown to be significantly decreased by Western immunoblotting. Thus, fomesafen is a unique chemical that inhibits both the oxidation of protoporphyrinogen as well as the conversion of uroporphyrinogen to coproporphyrinogen. However, the accumulation of highly carboxylated porphyrins is evident only after prolonged treatment with high doses of the herbicide.

Comprehensive analysis of the tryptophan metabolome in urine of patients with acute intermittent porphyria.

PubMed

Gomez-Gomez, Alex; Marcos, Josep; Aguilera, Paula; To-Figueras, Jordi; Pozo, Oscar J

2017-08-15

Acute intermittent porphyria (AIP) is a rare metabolic disorder due to a deficiency of porphobilinogen deaminase, the third enzyme of the heme biosynthetic pathway. This low enzymatic activity may predispose to the appearance of acute neurological attacks. Seminal studies suggested that AIP was associated with changes in tryptophan homeostasis with inconclusive results. Therefore, the aim of this study was to analyze the urinary metabolome of AIP patients focusing on tryptophan metabolism using state-of-the-art technology. This was a case-control study including a group of 25 AIP patients with active biochemical disease and increased excretion of heme-precursors and 25 healthy controls. Tryptophan and related compounds and metabolites including: large neutral amino acids (LNAAs), serotonin, kynurenine, kynurenic acid and anthranilic acid were quantified in urine by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Twenty-nine biological markers (including metabolic ratios and absolute concentrations) were compared between patients and controls. Significant differences were found in the tryptophan-kynurenine metabolic pathway. Compared to controls, AIP patients showed: (a) increased urinary excretion of kynurenine and anthranilic acid (P<0.005); (b): elevation of the kynurenine/tryptophan ratio (P<0.001) and (c): decrease of the kynurenic acid/kynurenine ratio (P=0.001). In contrast, no differences were found in the serotonin metabolic pathway independently of the markers and ratios used. The results of the study demonstrate that there is an imbalance in the kynurenine metabolic pathway in AIP patients, with an increase of the kynurenine/tryptophan ratio in urine and a reduction of the kynurenic acid/kynurenine ratio. The modified ratios suggest induction of indoleamine 2,3-deoxygenase and decreased activity of kynurenine aminotransferase in the liver. The results confirm that LC-MS/MS is useful for the characterization of the urinary metabolome of hepatic porphyrias. Copyright © 2017. Published by Elsevier B.V.

Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice.

PubMed

Iwadate, Reiko; Satoh, Yoko; Watanabe, Yukino; Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mashino, Tadahiko; Mitsumoto, Atsushi

2012-07-01

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (T(b)) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1-3 h in terms of the biological rhythms of T(b) or LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ~0.3 h shortening of the period of circadian T(b) rhythms in mice kept under conditions of constant darkness (P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg(-1)·day(-1)) or glucose (9 g·kg(-1)·day(-1)) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms (P < 0.05) and restored the decrease of heme (P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.

Gas chromatography-mass spectrometry profiling of steroids in urine of patients with acute intermittent porphyria.

PubMed

Casals, Gregori; Marcos, Josep; Pozo, Óscar J; Aguilera, Paula; Herrero, Carmen; To-Figueras, Jordi

2013-06-01

Acute intermittent porphyria (AIP) is an autosomal dominant disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers may present acute neurovisceral attacks with hepatic overproduction of heme-precursors. In some patients, remission of the acute symptoms leads to long-term hepatic metabolic abnormalities. In this study, gas chromatography-mass spectrometry (GC/MS) was used to investigate urinary steroid metabolome of AIP patients. Steroid profiling in urine was performed in a group of AIP patients with biochemically active disease (n=22) and healthy controls (n = 20). Five asymptomatic AIP family carriers were also studied. Commonly used ratios for the evaluation of disturbances in the steroid metabolism were calculated. We found that etiocholanolone/androsterone and tetrahydrocortisol/5α-tetrahydrocortisol (THF/5α-THF) metabolic ratios were significantly increased in the urine of AIP patients compared to controls (2.3 ± 0.3 vs 0.8 ± 0.1; p < 0.001 and 2.9 ± 0.7 vs 0.9 ± 0.1; p < 0.01). The (THF+5α-THF)/tetrahydrocortisone ratio was reduced among the AIP patients (p < 0.01). Quantification of the steroid absolute concentrations showed that these variations were due to a decrease of the 5α metabolites. Other ratios, like cortisol/cortisone and 6β-hydroxycortisol/cortisol in the free steroid fraction did not show differences between patients and controls. All ratios were normal among the family carriers. A significant number of AIP patients present a basal decrease of steroid 5α-reductase activity in the liver. The deficiency may be related to malnutrition and hepatic energy misbalance associated with active AIP. Urinary steroid profiling by GC/MS may be a valuable tool to assess hepatic metabolome in AIP. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Spectral design flexibility of LED brings better life

NASA Astrophysics Data System (ADS)

Ou, Haiyan; Corell, Dennis; Ou, Yiyu; Poulsen, Peter B.; Dam-Hansen, Carsten; Petersen, Paul-Michael

2012-03-01

Light-emitting diodes (LEDs) are penetrating into the huge market of general lighting because they are energy saving and environmentally friendly. The big advantage of LED light sources, compared to traditional incandescent lamps and fluorescent light tubes, is the flexible spectral design to make white light using different color mixing schemes. The spectral design flexibility of white LED light sources will promote them for novel applications to improve the life quality of human beings. As an initial exploration to make use of the spectral design flexibility, we present an example: 'no blue' white LED light source for sufferers of disease Porphyria. An LED light source prototype, made of high brightness commercial LEDs applying an optical filter, was tested by a patient suffering from Porphyria. Preliminary results have shown that the sufferer could withstand the light source for much longer time than the standard light source. At last future perspectives on spectral design flexibility of LED light sources improving human being's life will be discussed, with focus on the light and health. The good health is ensured by the spectrum optimized so that vital hormones (melatonin and serotonin) are produced during times when they support human daily rhythm.

A case of teriparatide-induced severe hypophosphatemia and hypercalcemia.

PubMed

Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Tanaka, Yoshiya

2014-09-01

PTH (teriparatide) is used in the treatment of osteoporosis, and can sometimes cause transient hypercalcemia, but to date there have been no reports of persistent hypercalcemia and hypophosphatemia resulting from its use. We describe a case with marked hypophosphatemia and hypercalcemia associated with the use of teriparatide. The patient was a 49-year-old woman who was followed up for acute intermittent porphyria and glucocorticoid-induced osteoporosis (following administration of prednisolone at 22.5 mg/day), and presented with unexplained fracture of the left tibia, for which treatment with teriparatide at 20 μg/day was started. Two weeks after treatment with teriparatide, the patient developed hypophosphatemia, hypercalcemia, hyperalkaline phosphatasemia, low TmP/GFR, FEca, BAP, and urinary NT×, with low intact PTH. These changes were considered to be related to teriparatide. Cessation of teriparatide treatment resulted in normalization of all parameters at 10 weeks (serum P 3.6 mg/dl, corrected Ca 8.8 mg/dl, ALP 273 IU/l, intact PTH 63 pg/ml). The observed abnormalities were considered to be in part related to acute intermittent porphyria, which is known to delay hepatic teriparatide clearance, with subsequent delay of PTH action despite its intermittent use, resulting in hypercalcemia and hypophosphatemia.

Photosensitive disorders in HIV

PubMed Central

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible. PMID:29568622

Photosensitive disorders in HIV.

PubMed

Koch, Karen

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible.

Soren Kierkegaard (1813-55): a bicentennial pathographical review.

PubMed

Schioldann, Johan; Søgaard, Ib

2013-12-01

Researchers in the fields of psychology, psychiatry, medicine and theology have made exhaustive efforts to shed light on the elusive biography/pathography of the great Danish philosopher Søren Kierkegaard (1813-55). This 'bicentennial' article reviews his main pathographical diagnoses of, respectively, possible manic-depressive [bipolar] disease, epilepsy, complex partial seizure disorder, Landry-Guillain-Barré's acute ascending paralysis, acute intermittent porphyria with possible psychiatric manifestations, and syphilidophobia.

[Factitious Disorder in Obstetrics: Case Report].

PubMed

Molano, Juan Carlos; Cortés, Natalia; Noguera, Efraín

2012-06-01

Munchhausen's syndrome is the best-studied type of factitious disorder with predominantly physical signs and symptoms. However, its clinical presentation during pregnancy is rare and literature on the subject is scarce. To present a case of factitious disorder during pregnancy. Review and analysis of a clinical case. The case of a 30-year-old woman six weeks pregnant who consults on multiple occasions with emesis and abdominal pain is discussed. Various different diagnoses were considered and pathologies such as acute intermittent porphyria, narcotic bowel syndrome, abdominal epilepsy, and esophageal spasm were discarded. The patient expressed her desire to terminate the pregnancy at week 21. The pregnancy was terminated after a medical panel concluded that there were both organic and mental conditions that placed the patient's health at risk. Factitious disorders are very complex and extremely challenging to the clinician especially during the initial phases. They are seldom suspected and rarely diagnosed even in hospital settings. Therefore it is of utmost importance to educate healthcare professionals in the detection of this disorder to ensure proper management and treatment. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Insulin resistance in porphyria cutanea tarda.

PubMed

Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

1989-06-01

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

PubMed

Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

2015-11-01

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

N-Alkylprotoporphyrin Formation and Hepatic Porphyria in Dogs After Administration of a New Antiepileptic Drug Candidate: Mechanism and Species Specificity

PubMed Central

Nicolas, Jean-Marie; Chanteux, Hugues; Mancel, Valérie; Dubin, Guy-Marie; Gerin, Brigitte; Staelens, Ludovicus; Depelchin, Olympe; Kervyn, Sophie

2014-01-01

A new antiepileptic synaptic vesicle 2a (SV2a) ligand drug candidate was tested in 4-week oral toxicity studies in rat and dog. Brown pigment inclusions were found in the liver of high-dose dogs. The morphology of the deposits and the accompanying liver changes (increased plasma liver enzymes, increased total hepatic porphyrin level, decreased liver ferrochelatase activity, combined induction, and inactivation of cytochrome P-450 CYP2B11) suggested disruption of the heme biosynthetic cascade. None of these changes was seen in rat although this species was exposed to higher parent drug levels. Toxicokinetic analysis and in vitro metabolism assays in hepatocytes showed that dog is more prone to oxidize the drug candidate than rat. Mass spectrometry analysis of liver samples from treated dogs revealed an N-alkylprotoporphyrin adduct. The elucidation of its chemical structure suggested that the drug transforms into a reactive metabolite which is structurally related to a known reference porphyrogenic agent allylisopropylacetamide. That particular metabolite, primarily produced in dog but neither in rat nor in human, has the potential to alkylate the prosthetic heme of CYP. Overall, the data suggested that the drug candidate should not be porphyrogenic in human. This case study further exemplifies the species variability in the susceptibility to drug-induced porphyria. PMID:24973095

Bullosis Diabeticorum: A Rare Presentation with Immunoglobulin G (IgG) Deposition Related Vasculopathy. Case Report and Focused Review

PubMed Central

Sonani, Hardik; Salim, Sohail Abdul; Garla, Vishnu V.; Wile, Anna; Palabindala, Venkataraman

2018-01-01

Patient: Male, 42 Final Diagnosis: Bullosis diabeticorum Symptoms: Skin rash Medication: — Clinical Procedure: Debridement Specialty: Metabolic Disorders and Diabetics Objective: Rare co-existance of disease or pathology Background: Bullosis diabeticorum (BD) is a condition characterized by recurrent, spontaneous, and non-inflammatory blistering in patients with poorly controlled diabetes mellitus. While etiopathogenesis remains unclear, roles of neuropathy, vasculopathy and UV light are hypothesized. Most literature reports negative direct and indirect immunofluorescence findings in diabetics with bullous eruptions. Porphyria cutanea tarda, bullous pemphigoid, epidermolysis bullosa, and pseudoporphyria are other differential diagnoses of bullous lesions, and they must be excluded. Case Report: We present a 42-year-old African American male with long standing poorly controlled insulin dependent diabetes mellitus with blisters on his left hand and feet. The blisters were noticed three weeks prior to presentation and, thereafter, rapidly increased in size and spontaneously ruptured. Physical examination revealed a multitude of both roofed and unroofed bullous painless skin lesions. Hematoxylin and eosin (H&E) staining dramatized the dermal-epidermal blistering and re-epithelization process. Direct Immunofluorescence (DIF) was positive for 2 + IgG deposition in the already thickened basement membrane of the capillaries of the superficial vascular plexus. After debridement, his wounds greatly improved with over three months of aggressive wound care. Conclusions: Primary immunologic abnormality likely plays no role in the onset of BD. To date, only one article has reported nonspecific capillary-associated immunoglobulin M and C3. This is the first case of BD with IgG deposition in the superficial capillary basement membrane. Positive findings on DIF suggest vasculopathy. Dermal microangiopathy, secondary to immunologic abnormality, is a possible underlying pathogenesis to bullae formation. Punch biopsy with DIF can be an additional diagnostic modality in the management of such cases. PMID:29332930

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria

PubMed Central

Brancaleoni, V.; Balwani, M.; Granata, F.; Graziadei, G.; Missineo, P.; Fiorentino, V.; Fustinoni, S.; Cappellini, M.D.; Naik, H.; Desnick, R.J.; Di Pierro, E.

2015-01-01

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

A new mutation within the porphobilinogen deaminase gene leading to a truncated protein as a cause of acute intermittent porphyria in an extended Indian family.

PubMed

Flachsová, E; Verma, I C; Ulbrichová, D; Saxena, R; Zeman, J; Saudek, V; Raman, C S; Martásek, P

2007-01-01

Based on Internet search, we were contacted by a 50-year-old man suffering from severe abdominal pain. Acute hepatic porphyria was considered from positive Watson-Schwartz test. He, not being a health professional, searched for centres with ability to do molecular diagnosis and for information about therapeutic possibilities. He asked his physician for haem-arginate (Normosang, Orphan Europe, Paris) treatment, arranged sending his blood to our laboratory and mediated genetic counselling for him and his family. Molecular analyses of the PBGD gene revealed a novel mutation in exon 15, the 973insG. Subsequently, genetic analysis was performed in 18 members of the proband's extensive family. In 12 members of the family, the same mutation was found. The mutation, which consisted of one nucleotide insertion, resulted in addition of four different amino acids leading to a protein that is prematurely truncated by the stop codon. The effect of this mutation was investigated by expression of the wildtype and mutated PBGD in a prokaryotic expression system. The mutation resulted in instability of the protein and loss of enzymatic function. The increasing access to a number of disease- and symptom-oriented web pages presents a new and unusual venue for gaining knowledge and enabling self-diagnosis and self-help. It is, therefore, important that diseaseoriented Internet pages for public use should be designed with clarity and accurate current knowledge based background.

Inherited disorders in the Afrikaner population of southern Africa. Part I. Historical and demographic background, cardiovascular, neurological, metabolic and intestinal conditions.

PubMed

Botha, M C; Beighton, P

1983-10-08

Certain genetic disorders occur with unusually high frequency in the Afrikaner population of southern Africa. Conditions of this type (reviewed in Part I of this article) include familial hypercholesterolaemia, progressive familial heart block, Huntington's chorea, porphyria variegata, Gaucher's disease, cystic fibrosis and familial colonic polyposis. This genetic situation is explicable to some extent on the basis of the demographic development of the Afrikaner population during the 14 generations since the arrival of the first immigrants from Holland more than 330 years ago.

Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

PubMed

Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

2016-04-01

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hepatitis C virus and its cutaneous manifestations: treatment in the direct-acting antiviral era.

PubMed

Wiznia, L E; Laird, M E; Franks, A G

2017-08-01

New all-oral direct-acting antivirals (DAA) have changed the hepatitis C virus (HCV) treatment landscape. Given that dermatologists frequently encounter HCV-infected patients, knowledge of the current treatment options and their utility in treating HCV-associated dermatologic disorders is important. In addition to highlighting the new treatment options, we review four classically HCV-associated dermatologic disorders - mixed cryoglobulinaemia (MC), lichen planus (LP), porphyria cutanea tarda (PCT) and necrolytic acral erythema (NAE) - and examine the role for all-oral direct-acting antiviral (DAA) regimens in their treatment. A literature search of English-language publications was conducted of the PubMed and EMBASE databases using search terms including 'hepatitis C', 'direct acting antivirals', 'cutaneous', 'mixed cryoglobulinemia', 'necrolytic acral erythema', 'lichen planus', 'porphyria cutanea tarda', 'rash', as well as specific drug names, related terms and abbreviations. Currently, limited data exist on the use of DAAs in HCV-infected patients with cutaneous side-effects, although treatment of the underlying HCV is now recommended for nearly all patients, with the new drugs offering much-improved dosage schedules and side-effect profiles. The most data exist for MC, in which several studies suggest that DAAs and achievement of sustained virologic response (SVR) improve cutaneous symptoms. Studies of both older and newer regimens are limited by their small size, retrospective nature, lack of appropriate controls and wide variability in study protocols. Given the strong association, screening for HCV should be considered in patients with MC, LP, PCT and NAE. © 2017 European Academy of Dermatology and Venereology.

Mass spectrometric characterisation of a condensation product between porphobilinogen and indolyl-3-acryloylglycine in urine of patients with acute intermittent porphyria.

PubMed

Marcos, Josep; Ibañez, Maria; Ventura, Rosa; Segura, Jordi; To-Figueras, Jordi; Pozo, Oscar J

2015-07-01

We document the presence of a previously unknown species in the urine of patients with acute intermittent porphyria (AIP). The compound was fully characterised by liquid chromatography tandem mass spectrometry. Interpretation of both full spectrum acquisition and product ion spectra acquired in positive and negative ionisation modes by quadrupole time of flight MS allowed for the identification of a condensation product arising from porphobilinogen (PBG, increased in the urine of AIP patients) and indolyl-3-acryloylglycine (IAG, derived from indolylacrylic acid and present in human urine). The structure was unequivocally confirmed through comparison between the selected reaction monitoring chromatograms obtained from the urinary species and the condensation product qualitatively synthesised in the laboratory. Owing to the large amounts of both PBG and IAG in urine of AIP patients, the possible ex vivo formation of PBG-IAG in urine samples was evaluated. The product was spontaneously formed at room temperature, at 4 °C and even during storage at -20 °C when spiking a control sample with PBG. A positive correlation was found between PBG and PBG-IAG in samples collected from AIP patients. However, no correlation was found between PBG-IAG and IAG. Purified PBG-IAG did not form the characteristic chromogen after application of p-dimethylaminobenzaldehyde in HCl, thus suggesting that the current techniques used to measure PBG in urine of AIP patients based on Ehlrich's reaction do not detect this newly characterised PBG-IAG fraction. Copyright © 2015 John Wiley & Sons, Ltd.

Representing Chronic Disorders of Consciousness:

PubMed Central

Hall, Alice

2014-01-01

This article explores problems of voicelessness in Isabel Allende’s Paula (1995) through a focus on the story of Paula’s illness and subsequent death from porphyria in 1992. I argue that the language, categories and stories through which disorders of consciousness are constructed are central to ethical decision-making and shifting cultural understandings of these conditions. In Paula, Allende uses an experimental, hybrid narrative form that draws on illness narrative, magical realist novel, national history, letters, and memoir to challenge traditional depictions of “coma” and to create a new public space through which these issues of voicelessness can be addressed. PMID:25055709

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

Low-Dose Hydroxychloroquine is as Effective as Phlebotomy in Treatment of Patients with Porphyria Cutanea Tarda

PubMed Central

Singal, Ashwani K.; Kormos-Hallberg, Csilla; Lee, Chul; Sadagoparamanujam, V.-M.; Grady, James J.; Freeman, Daniel H.; Anderson, Karl E.

2012-01-01

Background & Aims Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. Methods We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. Results The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. Conclusions Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. PMID:22985607

Hepatitis C virus core protein triggers abnormal porphyrin metabolism in human hepatocellular carcinoma cells.

PubMed

Nakano, Takafumi; Moriya, Kyoji; Koike, Kazuhiko; Horie, Toshiharu

2018-01-01

Porphyria cutanea tarda (PCT), the most common of the human porphyrias, arises from a deficiency of uroporphyrinogen decarboxylase. Studies have shown a high prevalence of hepatitis C virus (HCV) infection in patients with PCT. While these observations implicate HCV infection as a risk factor for PCT pathogenesis, the mechanism of interaction between the virus and porphyrin metabolism is unknown. This study aimed to assess the effect of HCV core protein on intracellular porphyrin metabolism to elucidate the link between HCV infection and PCT. The accumulation and excretion of porphyrins after treatment with 5-aminolevulinic acid, a porphyrin precursor, were compared between cells stably expressing HCV core protein and controls. Cells expressing HCV core protein had lower amounts of intracellular protoporphyrin IX and heme and had higher amounts of excreted coproporphyrin III, the oxidized form of coproporphyrinogen III, compared with controls. These observations suggest that HCV core protein affects porphyrin metabolism and facilitates the export of excess coproporphyrinogen III and/or coproporphyrin III, possibly via porphyrin transporters. Real-time PCR analysis revealed that the presence of HCV core protein increased the mRNA expression of porphyrin exporters ABCG2 and FLVCR1. Western blot analysis showed a higher expression level of FLVCR1, but not ABCG2, as well as a higher expression level of mature ALAS1, which is the rate-limiting enzyme in the heme synthesis pathway, in HCV core protein-expressing cells compared with controls. The data indicate that HCV core protein induced abnormal intracellular porphyrin metabolism, with an over-excretion of coproporphyrin III. These findings may partially account for the susceptibility of HCV-infected individuals to PCT development.

Diagnostic medical physicists and their clinical activities.

PubMed

Cypel, Yasmin S; Sunshine, Jonathan H

2004-02-01

The primary objective of this study was to obtain basic, descriptive information about medical physicists involved in diagnostic radiology-related activities, the diagnostic-related activities that they performed, and the time spent on these activities. A survey was sent to a randomly selected sample of 1511 medical physicists from July through October 2001 using primarily e-mail methods; a total of 851 surveys was received, for a response rate of 56%. Of these, 427 were responses from physicists who do partly or only clinical diagnostic medical physics; it is this group for which results are presented. Fifty-four percent of the physicists who reported doing any clinical diagnostic medical physics performed clinical activities only in diagnostic medical physics. Fourteen percent of all those doing clinical diagnostic medical physics were women. Over 97% of the physicists doing clinical diagnostic medical physics reported having graduate degrees in physics; 53% had PhDs. The mean total weekly hours worked by physicists doing clinical diagnostic medical physics was 42. Medical physicists doing only clinical diagnostic activities reported working approximately 40 hours weekly, whereas those doing partly clinical diagnostic medical physics reported working 14 hours weekly in the field (approximately one-third of their work time). Radiography and fluoroscopy, computed tomography, nuclear medicine, and mammography are all fields in which the majority of those doing any clinical diagnostic medical physics are active. Full-time physicists working only in diagnostic medical physics were responsible for a median of 25 units of equipment, compared with a median of 10 units for those working only partly in the field. Number of units evaluated, frequency of evaluation, and hours per evaluation were reported for almost 20 types of equipment. Medical physicists performing diagnostic clinical activities typically are responsible for a large number and wide variety of imaging equipment. It would be helpful to study their work further, focusing in particular on whether there is a shortage, as is true of diagnostic radiologists, and whether the variety of responsibilities creates strain.

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

PubMed

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

BRIEF REPORT: Beyond Clinical Experience: Features of Data Collection and Interpretation That Contribute to Diagnostic Accuracy

PubMed Central

Nendaz, Mathieu R; Gut, Anne M; Perrier, Arnaud; Louis-Simonet, Martine; Blondon-Choa, Katherine; Herrmann, François R; Junod, Alain F; Vu, Nu V

2006-01-01

BACKGROUND Clinical experience, features of data collection process, or both, affect diagnostic accuracy, but their respective role is unclear. OBJECTIVE, DESIGN Prospective, observational study, to determine the respective contribution of clinical experience and data collection features to diagnostic accuracy. METHODS Six Internists, 6 second year internal medicine residents, and 6 senior medical students worked up the same 7 cases with a standardized patient. Each encounter was audiotaped and immediately assessed by the subjects who indicated the reasons underlying their data collection. We analyzed the encounters according to diagnostic accuracy, information collected, organ systems explored, diagnoses evaluated, and final decisions made, and we determined predictors of diagnostic accuracy by logistic regression models. RESULTS Several features significantly predicted diagnostic accuracy after correction for clinical experience: early exploration of correct diagnosis (odds ratio [OR] 24.35) or of relevant diagnostic hypotheses (OR 2.22) to frame clinical data collection, larger number of diagnostic hypotheses evaluated (OR 1.08), and collection of relevant clinical data (OR 1.19). CONCLUSION Some features of data collection and interpretation are related to diagnostic accuracy beyond clinical experience and should be explicitly included in clinical training and modeled by clinical teachers. Thoroughness in data collection should not be considered a privileged way to diagnostic success. PMID:17105525

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Nonphysician practitioners (that is, clinical nurse specialists, clinical psychologists, clinical social... that do not involve the use of contrast media; and (iii) Diagnostic mammograms if the approved portable...

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.509 Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory...

Diagnostic reasoning strategies and diagnostic success.

PubMed

Coderre, S; Mandin, H; Harasym, P H; Fick, G H

2003-08-01

Cognitive psychology research supports the notion that experts use mental frameworks or "schemes", both to organize knowledge in memory and to solve clinical problems. The central purpose of this study was to determine the relationship between problem-solving strategies and the likelihood of diagnostic success. Think-aloud protocols were collected to determine the diagnostic reasoning used by experts and non-experts when attempting to diagnose clinical presentations in gastroenterology. Using logistic regression analysis, the study found that there is a relationship between diagnostic reasoning strategy and the likelihood of diagnostic success. Compared to hypothetico-deductive reasoning, the odds of diagnostic success were significantly greater when subjects used the diagnostic strategies of pattern recognition and scheme-inductive reasoning. Two other factors emerged as independent determinants of diagnostic success: expertise and clinical presentation. Not surprisingly, experts outperformed novices, while the content area of the clinical cases in each of the four clinical presentations demonstrated varying degrees of difficulty and thus diagnostic success. These findings have significant implications for medical educators. It supports the introduction of "schemes" as a means of enhancing memory organization and improving diagnostic success.

The Added Value of the Combined Use of the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule: Diagnostic Validity in a Clinical Swedish Sample of Toddlers and Young Preschoolers

ERIC Educational Resources Information Center

Zander, Eric; Sturm, Harald; Bölte, Sven

2015-01-01

The diagnostic validity of the new research algorithms of the Autism Diagnostic Interview-Revised and the revised algorithms of the Autism Diagnostic Observation Schedule was examined in a clinical sample of children aged 18-47 months. Validity was determined for each instrument separately and their combination against a clinical consensus…

Reducing Diagnostic Error with Computer-Based Clinical Decision Support

ERIC Educational Resources Information Center

Greenes, Robert A.

2009-01-01

Information technology approaches to delivering diagnostic clinical decision support (CDS) are the subject of the papers to follow in the proceedings. These will address the history of CDS and present day approaches (Miller), evaluation of diagnostic CDS methods (Friedman), and the role of clinical documentation in supporting diagnostic decision…

Skin diseases associated with Agent Orange and other organochlorine exposures.

PubMed

Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

2016-01-01

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

Archie Cochrane and his legacy. An internal challenge to physicians' autonomy?

PubMed

Hill, G B

2000-12-01

Archibald L. (Archie) Cochrane was born in 1909 into a wealthy Scottish family, from which he inherited the advantage of a private income and the disadvantage of porphyria. Though a brilliant student, his medical training was interrupted by a lengthy psychoanalysis in Europe, and by service in a field ambulance unit in the Spanish Civil War. Eventually Cochrane qualified in medicine in 1938 and joined the R.A.M.C. in 1939. He was taken prisoner in Crete in 1941 and served the rest of the war as medical officer in various POW camps. Cochrane's post-war career with the Medical Research Council as a field epidemiologist in South Wales earned him the respect and admiration of a generation of British epidemiologists. However, Cochrane's international reputation is not based on his achievements as an epidemiologist, but on his 1971 monograph "Effectiveness and Efficiency. Random Reflections on Health Services," a biting scientific critique of medical practice. Cochrane died in 1988, but his name lives on in the Cochrane Collaboration, a network of researchers devoted to clinical trials, and the torch which he lit had been carried forward by the groups promoting evidence-based medicine. Some have looked askance at these developments, regarding them as a threat to the autonomy of physicians.

The Importance of Considering Clinical Utility in the Construction of a Diagnostic Manual.

PubMed

Mullins-Sweatt, Stephanie N; Lengel, Gregory J; DeShong, Hilary L

2016-01-01

The development of major diagnostic manuals primarily has been guided by construct validity rather than clinical utility. The purpose of this article is to summarize recent research and theory examining the importance of clinical utility when constructing and evaluating a diagnostic manual. We suggest that construct validity is a necessary but not sufficient criterion for diagnostic constructs. This article discusses components of clinical utility and how these have applied to the current and forthcoming diagnostic manuals. Implications and suggestions for future research are provided.

Assessing clinical reasoning (ASCLIRE): Instrument development and validation.

PubMed

Kunina-Habenicht, Olga; Hautz, Wolf E; Knigge, Michel; Spies, Claudia; Ahlers, Olaf

2015-12-01

Clinical reasoning is an essential competency in medical education. This study aimed at developing and validating a test to assess diagnostic accuracy, collected information, and diagnostic decision time in clinical reasoning. A norm-referenced computer-based test for the assessment of clinical reasoning (ASCLIRE) was developed, integrating the entire clinical decision process. In a cross-sectional study participants were asked to choose as many diagnostic measures as they deemed necessary to diagnose the underlying disease of six different cases with acute or sub-acute dyspnea and provide a diagnosis. 283 students and 20 content experts participated. In addition to diagnostic accuracy, respective decision time and number of used relevant diagnostic measures were documented as distinct performance indicators. The empirical structure of the test was investigated using a structural equation modeling approach. Experts showed higher accuracy rates and lower decision times than students. In a cross-sectional comparison, the diagnostic accuracy of students improved with the year of study. Wrong diagnoses provided by our sample were comparable to wrong diagnoses in practice. We found an excellent fit for a model with three latent factors-diagnostic accuracy, decision time, and choice of relevant diagnostic information-with diagnostic accuracy showing no significant correlation with decision time. ASCLIRE considers decision time as an important performance indicator beneath diagnostic accuracy and provides evidence that clinical reasoning is a complex ability comprising diagnostic accuracy, decision time, and choice of relevant diagnostic information as three partly correlated but still distinct aspects.

The STARD statement for reporting diagnostic accuracy studies: application to the history and physical examination.

PubMed

Simel, David L; Rennie, Drummond; Bossuyt, Patrick M M

2008-06-01

The Standards for Reporting of Diagnostic Accuracy (STARD) statement provided guidelines for investigators conducting diagnostic accuracy studies. We reviewed each item in the statement for its applicability to clinical examination diagnostic accuracy research, viewing each discrete aspect of the history and physical examination as a diagnostic test. Nonsystematic review of the STARD statement. Two former STARD Group participants and 1 editor of a journal series on clinical examination research reviewed each STARD item. Suggested interpretations and comments were shared to develop consensus. The STARD Statement applies generally well to clinical examination diagnostic accuracy studies. Three items are the most important for clinical examination diagnostic accuracy studies, and investigators should pay particular attention to their requirements: describe carefully the patient recruitment process, describe participant sampling and address if patients were from a consecutive series, and describe whether the clinicians were masked to the reference standard tests and whether the interpretation of the reference standard test was masked to the clinical examination components or overall clinical impression. The consideration of these and the other STARD items in clinical examination diagnostic research studies would improve the quality of investigations and strengthen conclusions reached by practicing clinicians. The STARD statement provides a very useful framework for diagnostic accuracy studies. The group correctly anticipated that there would be nuances applicable to studies of the clinical examination. We offer guidance that should enhance their usefulness to investigators embarking on original studies of a patient's history and physical examination.

Benefit-risk Evaluation for Diagnostics: A Framework (BED-FRAME).

PubMed

Evans, Scott R; Pennello, Gene; Pantoja-Galicia, Norberto; Jiang, Hongyu; Hujer, Andrea M; Hujer, Kristine M; Manca, Claudia; Hill, Carol; Jacobs, Michael R; Chen, Liang; Patel, Robin; Kreiswirth, Barry N; Bonomo, Robert A

2016-09-15

The medical community needs systematic and pragmatic approaches for evaluating the benefit-risk trade-offs of diagnostics that assist in medical decision making. Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) is a strategy for pragmatic evaluation of diagnostics designed to supplement traditional approaches. BED-FRAME evaluates diagnostic yield and addresses 2 key issues: (1) that diagnostic yield depends on prevalence, and (2) that different diagnostic errors carry different clinical consequences. As such, evaluating and comparing diagnostics depends on prevalence and the relative importance of potential errors. BED-FRAME provides a tool for communicating the expected clinical impact of diagnostic application and the expected trade-offs of diagnostic alternatives. BED-FRAME is a useful fundamental supplement to the standard analysis of diagnostic studies that will aid in clinical decision making. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

PubMed

Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

2015-01-01

In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

The STARD Statement for Reporting Diagnostic Accuracy Studies: Application to the History and Physical Examination

PubMed Central

Rennie, Drummond; Bossuyt, Patrick M. M.

2008-01-01

Summary Objective The Standards for Reporting of Diagnostic Accuracy (STARD) statement provided guidelines for investigators conducting diagnostic accuracy studies. We reviewed each item in the statement for its applicability to clinical examination diagnostic accuracy research, viewing each discrete aspect of the history and physical examination as a diagnostic test. Setting Nonsystematic review of the STARD statement. Interventions Two former STARD Group participants and 1 editor of a journal series on clinical examination research reviewed each STARD item. Suggested interpretations and comments were shared to develop consensus. Measurements and Main Results The STARD Statement applies generally well to clinical examination diagnostic accuracy studies. Three items are the most important for clinical examination diagnostic accuracy studies, and investigators should pay particular attention to their requirements: describe carefully the patient recruitment process, describe participant sampling and address if patients were from a consecutive series, and describe whether the clinicians were masked to the reference standard tests and whether the interpretation of the reference standard test was masked to the clinical examination components or overall clinical impression. The consideration of these and the other STARD items in clinical examination diagnostic research studies would improve the quality of investigations and strengthen conclusions reached by practicing clinicians. Conclusions The STARD statement provides a very useful framework for diagnostic accuracy studies. The group correctly anticipated that there would be nuances applicable to studies of the clinical examination. We offer guidance that should enhance their usefulness to investigators embarking on original studies of a patient’s history and physical examination. PMID:18347878

Current Concepts in Dermatology

PubMed Central

Jackson, Robert

1963-01-01

Many systemic diseases have cutaneous manifestations. In some diseases skin involvement is the predominant factor (Behçet's syndrome, urticaria pigmentosa, discoid lupus erythematosus and pseudoxanthoma elasticum); in others the skin manifestations, when present, are an important part of the condition (sarcoidosis, systemic lupus erythematosus, hypersensitivity angiitis, porphyria). This report includes descriptions of and comments on these cutaneous manifestations. Erythema nodosum and erythema multiforme are reaction patterns of the skin and mucous membrane which may have many causes. The relationship between discoid and systemic lupus erythematosus is discussed. There is little doubt that these are variations of the same basic disease process, even though the prognoses are very different. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14063940

PCB residues in the adipose tissue of the population of Barcelona (Spain)

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

Gomez-Catalan, J.; Sabroso, M.; To-Figueras, J.

1991-10-01

Polychlorinated biphenyls (PCBs) are a class of aryl halides widely distributed in the environment. Although production has virtually ceased, and most industrial applications (capacitors, transformers, hydraulic fluids, lubricants, etc) are severely restricted, they are one of the most ubiquitous and persistent environmental pollutants. Several toxic effects caused by PCBs have been described including: liver enlargement, hepatomegalocytosis, acne, lymphoid atrophy, immunosuppression, tumor promotion, porphyria. This work continues the authors' previous reports about organochlorine residues in human tissues of some Spanish populations, that showed high levels of some residues, specially of hexachlorobenzene (HCB). PCBs pattern and concentration in the adipose tissue ofmore » the inhabitants of an urban and industrial area (Barcelona) were determined.« less

Exploring cognitive integration of basic science and its effect on diagnostic reasoning in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2016-06-01

Integration of basic and clinical science knowledge is increasingly being recognized as important for practice in the health professions. The concept of 'cognitive integration' places emphasis on the value of basic science in providing critical connections to clinical signs and symptoms while accounting for the fact that clinicians may not spontaneously articulate their use of basic science knowledge in clinical reasoning. In this study we used a diagnostic justification test to explore the impact of integrated basic science instruction on novices' diagnostic reasoning process. Participants were allocated to an integrated basic science or clinical science training group. The integrated basic science group was taught the clinical features along with the underlying causal mechanisms of four musculoskeletal pathologies while the clinical science group was taught only the clinical features. Participants completed a diagnostic accuracy test immediately after initial learning, and one week later a diagnostic accuracy and justification test. The results showed that novices who learned the integrated causal mechanisms had superior diagnostic accuracy and better understanding of the relative importance of key clinical features. These findings further our understanding of cognitive integration by providing evidence of the specific changes in clinical reasoning when basic and clinical sciences are integrated during learning.

[The quality management in clinical diagnostic laboratory in conditions of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary)].

PubMed

Nikolaev, N S; Nazarova, V V; Dobrovol'skaia, N Iu; Orlova, A V; Pchelova, N N

2014-10-01

The article presents experience of clinical diagnostic laboratory of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary) in the area of quality management of medical laboratory services on the basis of evaluation of efficacy and effectiveness of processes. The factors effecting quality of functioning of clinical diagnostic laboratory are indicated. The criteria and indicators of efficacy of work of employees of clinical diagnostic laboratory are presented.

Overcoming regulatory and economic challenges facing pharmacogenomics.

PubMed

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

Implementation of Point-of-Care Diagnostics in Rural Primary Healthcare Clinics in South Africa: Perspectives of Key Stakeholders.

PubMed

Mashamba-Thompson, Tivani P; Jama, Ngcwalisa A; Sartorius, Benn; Drain, Paul K; Thompson, Rowan M

2017-01-08

Key stakeholders' involvement is crucial to the sustainability of quality point-of-care (POC) diagnostics services in low-and-middle income countries. The aim of this study was to explore key stakeholder perceptions on the implementation of POC diagnostics in rural primary healthcare (PHC) clinics in South Africa. We conducted a qualitative study encompassing in-depth interviews with multiple key stakeholders of POC diagnostic services for rural and resource-limited PHC clinics. Interviews were digitally recorded and transcribed verbatim prior to thematic content analysis. Thematic content analysis was conducted using themes guided by the World Health Organisation (WHO) quality-ASSURED (Affordable, Sensitive, Specific, User friendly, Rapid and to enable treatment at first visit and Robust, Equipment free and Delivered to those who need it) criteria for POC diagnostic services in resource-limited settings. 11 key stakeholders participated in the study. All stakeholders perceived the main advantage of POC diagnostics as enabling access to healthcare for rural patients. Stakeholders perceived the current POC diagnostic services to have an ability to meet patients' needs, but recommended further improvement of the following areas: research on cost-effectiveness; improved quality management systems; development of affordable POC diagnostic and clinic-based monitoring and evaluation. Key stakeholders of POC diagnostics in rural PHC clinics in South Africa highlighted the need to assess affordability and ensure quality assurance of current services before adopting new POC diagnostics and scaling up current POC diagnostics.

Implementation of Point-of-Care Diagnostics in Rural Primary Healthcare Clinics in South Africa: Perspectives of Key Stakeholders

PubMed Central

Mashamba-Thompson, Tivani P.; Jama, Ngcwalisa A.; Sartorius, Benn; Drain, Paul K.; Thompson, Rowan M.

2017-01-01

Introduction: Key stakeholders’ involvement is crucial to the sustainability of quality point-of-care (POC) diagnostics services in low-and-middle income countries. The aim of this study was to explore key stakeholder perceptions on the implementation of POC diagnostics in rural primary healthcare (PHC) clinics in South Africa. Method: We conducted a qualitative study encompassing in-depth interviews with multiple key stakeholders of POC diagnostic services for rural and resource-limited PHC clinics. Interviews were digitally recorded and transcribed verbatim prior to thematic content analysis. Thematic content analysis was conducted using themes guided by the World Health Organisation (WHO) quality-ASSURED (Affordable, Sensitive, Specific, User friendly, Rapid and to enable treatment at first visit and Robust, Equipment free and Delivered to those who need it) criteria for POC diagnostic services in resource-limited settings. Results: 11 key stakeholders participated in the study. All stakeholders perceived the main advantage of POC diagnostics as enabling access to healthcare for rural patients. Stakeholders perceived the current POC diagnostic services to have an ability to meet patients’ needs, but recommended further improvement of the following areas: research on cost-effectiveness; improved quality management systems; development of affordable POC diagnostic and clinic-based monitoring and evaluation. Conclusions: Key stakeholders of POC diagnostics in rural PHC clinics in South Africa highlighted the need to assess affordability and ensure quality assurance of current services before adopting new POC diagnostics and scaling up current POC diagnostics. PMID:28075337

The Importance of Conditional Probability in Diagnostic Reasoning and Clinical Decision Making: A Primer for the Eye Care Practitioner.

PubMed

Sanfilippo, Paul G; Hewitt, Alex W; Mackey, David A

2017-04-01

To outline and detail the importance of conditional probability in clinical decision making and discuss the various diagnostic measures eye care practitioners should be aware of in order to improve the scope of their clinical practice. We conducted a review of the importance of conditional probability in diagnostic testing for the eye care practitioner. Eye care practitioners use diagnostic tests on a daily basis to assist in clinical decision making and optimizing patient care and management. These tests provide probabilistic information that can enable the clinician to increase (or decrease) their level of certainty about the presence of a particular condition. While an understanding of the characteristics of diagnostic tests are essential to facilitate proper interpretation of test results and disease risk, many practitioners either confuse or misinterpret these measures. In the interests of their patients, practitioners should be aware of the basic concepts associated with diagnostic testing and the simple mathematical rule that underpins them. Importantly, the practitioner needs to recognize that the prevalence of a disease in the population greatly determines the clinical value of a diagnostic test.

Evaluating Diagnostic Point-of-Care Tests in Resource-Limited Settings

PubMed Central

Drain, Paul K; Hyle, Emily P; Noubary, Farzad; Freedberg, Kenneth A; Wilson, Douglas; Bishai, William; Rodriguez, William; Bassett, Ingrid V

2014-01-01

Diagnostic point-of-care (POC) testing is intended to minimize the time to obtain a test result, thereby allowing clinicians and patients to make an expeditious clinical decision. As POC tests expand into resource-limited settings (RLS), the benefits must outweigh the costs. To optimize POC testing in RLS, diagnostic POC tests need rigorous evaluations focused on relevant clinical outcomes and operational costs, which differ from evaluations of conventional diagnostic tests. Here, we reviewed published studies on POC testing in RLS, and found no clearly defined metric for the clinical utility of POC testing. Therefore, we propose a framework for evaluating POC tests, and suggest and define the term “test efficacy” to describe a diagnostic test’s capacity to support a clinical decision within its operational context. We also proposed revised criteria for an ideal diagnostic POC test in resource-limited settings. Through systematic evaluations, comparisons between centralized diagnostic testing and novel POC technologies can be more formalized, and health officials can better determine which POC technologies represent valuable additions to their clinical programs. PMID:24332389

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria.

PubMed

Burden-Teh, E; Phillips, R C; Thomas, K S; Ratib, S; Grindlay, D; Murphy, R

2017-11-06

The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardize patient recruitment into clinical trials and case definitions in observational studies. The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis. A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was to record the sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool. Twenty-three studies met the inclusion criteria. None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, and questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (> 90%) were reported in many studies. However, the study authors often did not specify how the criteria would be used clinically or in research. This review identified studies with varying risk of bias, and due to each study developing separate criteria meta-analysis was not possible. Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ study designs allowing high-quality diagnostic accuracy testing. Existing and newly developed criteria require validation. © 2017 British Association of Dermatologists.

Molecular pathology curriculum for medical laboratory scientists: A report of the association for molecular pathology training and education committee.

PubMed

Taylor, Sara; Bennett, Katie M; Deignan, Joshua L; Hendrix, Ericka C; Orton, Susan M; Verma, Shalini; Schutzbank, Ted E

2014-05-01

Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic contributions to specific diseases and the technologies used in molecular diagnostics laboratories change rapidly, challenging providers of training programs in molecular diagnostics to keep their curriculum current and relevant. In this article, we provide curriculum recommendations to molecular diagnostics training providers at both the baccalaureate and master's level of education. We base our recommendations on several factors. First, we considered National Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation of molecular diagnostics programs, because educational programs in clinical laboratory science should obtain its accreditation. Second, the guidelines of several of the best known certifying agencies for clinical laboratory scientists were incorporated into our recommendations. Finally, we relied on feedback from current employers of molecular diagnostics scientists, regarding the skills and knowledge that they believe are essential for clinical scientists who will be performing molecular testing in their laboratories. We have compiled these data into recommendations for a molecular diagnostics curriculum at both the baccalaureate and master's level of education. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Decision analysis to complete diagnostic research by closing the gap between test characteristics and cost-effectiveness.

PubMed

Schaafsma, Joanna D; van der Graaf, Yolanda; Rinkel, Gabriel J E; Buskens, Erik

2009-12-01

The lack of a standard methodology in diagnostic research impedes adequate evaluation before implementation of constantly developing diagnostic techniques. We discuss the methodology of diagnostic research and underscore the relevance of decision analysis in the process of evaluation of diagnostic tests. Overview and conceptual discussion. Diagnostic research requires a stepwise approach comprising assessment of test characteristics followed by evaluation of added value, clinical outcome, and cost-effectiveness. These multiple goals are generally incompatible with a randomized design. Decision-analytic models provide an important alternative through integration of the best available evidence. Thus, critical assessment of clinical value and efficient use of resources can be achieved. Decision-analytic models should be considered part of the standard methodology in diagnostic research. They can serve as a valid alternative to diagnostic randomized clinical trials (RCTs).

Clinical Diagnosis of Dental Caries in the 21st Century: Introductory Paper - ORCA Saturday Afternoon Symposium, 2016.

PubMed

Machiulskiene, Vita; Carvalho, Joana Christina

2018-03-05

Classifications employed to measure dental caries should first of all reflect the dynamics of the disease, in order to provide a solid basis for subsequent treatment decisions and for further monitoring of dental health of individual patients and populations. The contemporary philosophy of dental caries management implies that nonoperative treatment of caries lesions should be implemented whenever possible, limiting operative interventions to the severe and irreversible cases. The ORCA Saturday Afternoon Symposium 2016, held back-to-back to the 63rd ORCA Congress in Athens, Greece, was intended to provide an update on general requirements for clinical caries diagnosis and to overview caries diagnostic classifications including their rationale, validation, advantages, and limitations. Clinical caries diagnostic criteria and caries management outcomes are interrelated, and any diagnostic classification disregarding this concept is outdated, according to the current understanding of oral health care. Choosing clinical caries diagnostic classifications that assess the activity status of detected lesions should be a priority for dental professionals since these classifications favor the best clinical practice directed towards nonoperative interventions. The choice of clinical caries diagnostic classifications in research, in clinical practice, and in public health services should be guided by the best available scientific evidence. The clinical caries diagnostic classifications should be universally applicable in all these fields. Policy making in oral health care and the underlying policy analyses should follow the same standards. Any clinical caries diagnostic classification disregarding the universality of its use is of limited or no interest in the context of the clinical caries diagnosis of today. © 2018 S. Karger AG, Basel.

Clinical Application of Genome and Exome Sequencing as a Diagnostic Tool for Pediatric Patients: a Scoping Review of the Literature.

PubMed

Smith, Hadley Stevens; Swint, J Michael; Lalani, Seema R; Yamal, Jose-Miguel; de Oliveira Otto, Marcia C; Castellanos, Stephan; Taylor, Amy; Lee, Brendan H; Russell, Heidi V

2018-05-14

Availability of clinical genomic sequencing (CGS) has generated questions about the value of genome and exome sequencing as a diagnostic tool. Analysis of reported CGS application can inform uptake and direct further research. This scoping literature review aims to synthesize evidence on the clinical and economic impact of CGS. PubMed, Embase, and Cochrane were searched for peer-reviewed articles published between 2009 and 2017 on diagnostic CGS for infant and pediatric patients. Articles were classified according to sample size and whether economic evaluation was a primary research objective. Data on patient characteristics, clinical setting, and outcomes were extracted and narratively synthesized. Of 171 included articles, 131 were case reports, 40 were aggregate analyses, and 4 had a primary economic evaluation aim. Diagnostic yield was the only consistently reported outcome. Median diagnostic yield in aggregate analyses was 33.2% but varied by broad clinical categories and test type. Reported CGS use has rapidly increased and spans diverse clinical settings and patient phenotypes. Economic evaluations support the cost-saving potential of diagnostic CGS. Multidisciplinary implementation research, including more robust outcome measurement and economic evaluation, is needed to demonstrate clinical utility and cost-effectiveness of CGS.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia.

PubMed

Ahmad, Riris Andono; Matthys, Francine; Dwihardiani, Bintari; Rintiswati, Ning; de Vlas, Sake J; Mahendradhata, Yodi; van der Stuyft, Patrick

2012-02-15

Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

Autoimmune diagnostics: the technology, the strategy and the clinical governance.

PubMed

Bizzaro, Nicola; Tozzoli, Renato; Villalta, Danilo

2015-02-01

In recent years, there has been a profound change in autoimmune diagnostics. From long, tiring and inaccurate manual methods, the art of diagnostics has turned to modern, rapid and automated technology. New antibody tests have been developed, and almost all autoimmune diseases now have some specific diagnostic markers. The current need to make the most of available economic and human resources has led to the production of diagnostic algorithms and guidelines designated for optimal strategic use of the tests and to increase the diagnostic appropriateness. An important role in this scenario was assumed by the laboratory autoimmunologist, whose task is not only to govern the analytical phase, but also to help clinicians in correctly choosing the most suitable test for each clinical situation and provide consultancy support. In this review, we summarize recent advances in technology, describe the diagnostic strategies and highlight the current role of the laboratory autoimmunologist in the clinical governance of autoimmune diagnostics.

A semi-automated, field-portable microscopy platform for clinical diagnostic applications

NASA Astrophysics Data System (ADS)

Jagannadh, Veerendra Kalyan; Srinivasan, Rajesh; Gorthi, Sai Siva

2015-08-01

Clinical microscopy is a versatile diagnostic platform used for diagnosis of a multitude of diseases. In the recent past, many microfluidics based point-of-care diagnostic devices have been developed, which serve as alternatives to microscopy. However, these point-of-care devices are not as multi-functional and versatile as clinical microscopy. With the use of custom designed optics and microfluidics, we have developed a versatile microscopy-based cellular diagnostic platform, which can be used at the point of care. The microscopy platform presented here is capable of detecting infections of very low parasitemia level (in a very small quantity of sample), without the use of any additional computational hardware. Such a cost-effective and portable diagnostic device, would greatly impact the quality of health care available to people living in rural locations of the world. Apart from clinical diagnostics, it's applicability to field research in environmental microbiology has also been outlined.

Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development

PubMed Central

Poste, George; Carbone, David P.; Parkinson, David R.; Verweij, Jaap; Hewitt, Stephen; Jessup, J. Milburn

2012-01-01

Molecular diagnostics are increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, or to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify pharmocogenetic risk of adverse drug reactions. The articles of this CCR Focus section on Molecular Diagnosis describe the development and use of markers for medical decision-making in the cancer patient. They define the sources of preanalytic variability to minimize as well as the regulatory and financial challenges in diagnostic development and integration into clinical practice. They also outline an NCI program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation with sufficient sensitivity, specificity and validity that is comparable to that used for development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval. A way to accomplish this is to emphasize Phase IV post-marketing hypothesis driven clinical trials with biological characterization that permits accurate definition of the association of low prevalence gene alterations with toxicity or response in large cohorts. PMID:22422403

Leveling the playing field: bringing development of biomarkers and molecular diagnostics up to the standards for drug development.

PubMed

Poste, George; Carbone, David P; Parkinson, David R; Verweij, Jaap; Hewitt, Stephen M; Jessup, J Milburn

2012-03-15

Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.

[Clinical decision making and critical thinking in the nursing diagnostic process].

PubMed

Müller-Staub, Maria

2006-10-01

The daily routine requires complex thinking processes of nurses, but clinical decision making and critical thinking are underestimated in nursing. A great demand for educational measures in clinical judgement related with the diagnostic process was found in nurses. The German literature hardly describes nursing diagnoses as clinical judgements about human reactions on health problems / life processes. Critical thinking is described as an intellectual, disciplined process of active conceptualisation, application and synthesis of information. It is gained through observation, experience, reflection and communication and leads thinking and action. Critical thinking influences the aspects of clinical decision making a) diagnostic judgement, b) therapeutic reasoning and c) ethical decision making. Human reactions are complex processes and in their course, human behavior is interpreted in the focus of health. Therefore, more attention should be given to the nursing diagnostic process. This article presents the theoretical framework of the paper "Clinical decision making: Fostering critical thinking in the nursing diagnostic process through case studies".

The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples

PubMed Central

Erlandsson, Lena; Rosenstierne, Maiken W.; McLoughlin, Kevin; Jaing, Crystal; Fomsgaard, Anders

2011-01-01

A common technique used for sensitive and specific diagnostic virus detection in clinical samples is PCR that can identify one or several viruses in one assay. However, a diagnostic microarray containing probes for all human pathogens could replace hundreds of individual PCR-reactions and remove the need for a clear clinical hypothesis regarding a suspected pathogen. We have established such a diagnostic platform for random amplification and subsequent microarray identification of viral pathogens in clinical samples. We show that Phi29 polymerase-amplification of a diverse set of clinical samples generates enough viral material for successful identification by the Microbial Detection Array, demonstrating the potential of the microarray technique for broad-spectrum pathogen detection. We conclude that this method detects both DNA and RNA virus, present in the same sample, as well as differentiates between different virus subtypes. We propose this assay for diagnostic analysis of viruses in clinical samples. PMID:21853040

Final-year diagnostic radiography students' perception of role models within the profession.

PubMed

Conway, Alinya; Lewis, Sarah; Robinson, John

2008-01-01

Within a clinical education setting, the value of role models and prescribed mentors can be seen as an important influence in shaping the student's future as a diagnostic radiographer. A study was undertaken to create a new understanding of how diagnostic radiography students perceive role models and professional behavior in the workforce. The study aimed to determine the impact of clinical education in determining modeling expectations, role model identification and attributes, and the integration of academic education and "hands-on" clinical practice in preparing diagnostic radiography students to enter the workplace. Thirteen final-year (third-year) diagnostic radiography students completed an hour-long interview regarding their experiences and perceptions of role models while on clinical placement. The key concepts that emerged illustrated that students gravitate toward radiographers who enjoy sharing practical experiences with students and are good communicators. Unique to diagnostic radiography, students made distinctions about the presence of role models in private versus public service delivery. This study gives insight to clinical educators in diagnostic radiography and wider allied health into how students perceive role models, interact with preceptors, and combine real-life experiences with formal learning.

Definitions and diagnosis of postpartum endometritis in dairy cows.

PubMed

Dubuc, J; Duffield, T F; Leslie, K E; Walton, J S; LeBlanc, S J

2010-11-01

The objectives of this observational study were to determine and compare diagnostic criteria for postpartum endometritis in dairy cows. Data generated from 1,044 Holstein cows (6 herds) enrolled in a randomized clinical trial were used. Cows were examined for endometritis at 35±3 d (exam 1) and 56±3 d (exam 2) after parturition, using endometrial cytology (cytobrush technique), vaginal discharge scoring (Metricheck device; Simcrotech, Hamilton, New Zealand), and cervical diameter measurement (transrectal palpation). Reproductive data were recorded until 200 d after parturition. Diagnostic criteria for cytological and clinical endometritis were determined based on detrimental effect on subsequent reproductive performance, using logistic regression and Cox proportional hazard models accounting for the effect of herd clustering. Comparison of diagnostic criteria was performed using endometrial cytology as reference test or by quantifying the agreement between diagnostic approaches. At exam 1, diagnostic criteria were ≥6% polymorphonuclear cells and mucopurulent or worse (purulent or foul) vaginal discharge for cytological and clinical endometritis, respectively. At exam 2, diagnostic criteria were ≥4% polymorphonuclear cells and mucopurulent or worse vaginal discharge for cytological and clinical endometritis, respectively. Cows were classified as having cytological endometritis only, clinical endometritis only, or both cytological and clinical endometritis. Prevalence at exam 1 was 13.5, 9.4, and 5.8% for cytological endometritis only, clinical endometritis only, and both cytological and clinical endometritis, respectively. The detrimental effects of cytological and clinical endometritis on reproductive performance were additive. Among cows with clinical endometritis, only 38 and 36% had cytological endometritis at exam 1 and exam 2, respectively. Combination of diagnostic criteria improved neither the accuracy for predicting cytological endometritis nor the agreement between cytological and clinical endometritis. Overall, these results suggested that cytological and clinical endometritis may represent different manifestations of reproductive tract disease. They also suggested that use of the terminology clinical endometritis may not be accurate and that purulent vaginal discharge may be more descriptive. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Quantitative optical diagnostics in pathology recognition and monitoring of tissue reaction to PDT

NASA Astrophysics Data System (ADS)

Kirillin, Mikhail; Shakhova, Maria; Meller, Alina; Sapunov, Dmitry; Agrba, Pavel; Khilov, Alexander; Pasukhin, Mikhail; Kondratieva, Olga; Chikalova, Ksenia; Motovilova, Tatiana; Sergeeva, Ekaterina; Turchin, Ilya; Shakhova, Natalia

2017-07-01

Optical coherence tomography (OCT) is currently actively introduced into clinical practice. Besides diagnostics, it can be efficiently employed for treatment monitoring allowing for timely correction of the treatment procedure. In monitoring of photodynamic therapy (PDT) traditionally employed fluorescence imaging (FI) can benefit from complementary use of OCT. Additional diagnostic efficiency can be derived from numerical processing of optical diagnostics data providing more information compared to visual evaluation. In this paper we report on application of OCT together with numerical processing for clinical diagnostic in gynecology and otolaryngology, for monitoring of PDT in otolaryngology and on OCT and FI applications in clinical and aesthetic dermatology. Image numerical processing and quantification provides increase in diagnostic accuracy. Keywords: optical coherence tomography, fluorescence imaging, photod

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) or § 414.509(a)(3) that the basis for payment for a new test will be gapfilling, CMS posts interim... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests...

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

PubMed

Graham, Stephen M; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E; Gale, Marianne; Gie, Robert P; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J; McNeeley, David F; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R; Swaminathan, Soumya; Wingfield, Claire

2012-05-15

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

Whole exome sequencing in neurogenetic odysseys: An effective, cost- and time-saving diagnostic approach.

PubMed

Córdoba, Marta; Rodriguez-Quiroga, Sergio Alejandro; Vega, Patricia Analía; Salinas, Valeria; Perez-Maturo, Josefina; Amartino, Hernán; Vásquez-Dusefante, Cecilia; Medina, Nancy; González-Morón, Dolores; Kauffman, Marcelo Andrés

2018-01-01

Diagnostic trajectories for neurogenetic disorders frequently require the use of considerable time and resources, exposing patients and families to so-called "diagnostic odysseys". Previous studies have provided strong evidence for increased diagnostic and clinical utility of whole-exome sequencing in medical genetics. However, specific reports assessing its utility in a setting such as ours- a neurogeneticist led academic group serving in a low-income country-are rare. To assess the diagnostic yield of WES in patients suspected of having a neurogenetic condition and explore the cost-effectiveness of its implementation in a research group located in an Argentinean public hospital. This is a prospective study of the clinical utility of WES in a series of 40 consecutive patients selected from a Neurogenetic Clinic of a tertiary Hospital in Argentina. We evaluated patients retrospectively for previous diagnostic trajectories. Diagnostic yield, clinical impact on management and economic diagnostic burden were evaluated. We demonstrated the clinical utility of Whole Exome Sequencing in our patient cohort, obtaining a diagnostic yield of 40% (95% CI, 24.8%-55.2%) among a diverse group of neurological disorders. The average age at the time of WES was 23 (range 3-70). The mean time elapsed from symptom onset to WES was 11 years (range 3-42). The mean cost of the diagnostic workup prior to WES was USD 1646 (USD 1439 to 1853), which is 60% higher than WES cost in our center. WES for neurogenetics proved to be an effective, cost- and time-saving approach for the molecular diagnosis of this heterogeneous and complex group of patients.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

PubMed Central

2012-01-01

Background Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. Methods We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Results Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. Conclusions The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care. PMID:22333111

The Reliability and Criterion Validity of the Diagnostic Infant and Preschool Assessment: A New Diagnostic Instrument for Young Children

ERIC Educational Resources Information Center

Scheeringa, Michael S.; Haslett, Nancy

2010-01-01

The need to assess Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) disorders in children younger than 7 years of age has intensified as clinical efforts to diagnose and treat this population have increased, and clinical research on psychopathology has advanced. A new diagnostic instrument for young children was created, the Diagnostic…

The clinical inadequacy of the DSM-5 classification of somatic symptom and related disorders: an alternative trans-diagnostic model.

PubMed

Cosci, Fiammetta; Fava, Giovanni A

2016-08-01

The Diagnostic and Statistical of Mental Disorders, Fifth Edition (DSM-5) somatic symptom and related disorders chapter has a limited clinical utility. In addition to the problems that the single diagnostic rubrics and the deletion of the diagnosis of hypochondriasis entail, there are 2 major ambiguities: (1) the use of the term "somatic symptoms" reflects an ill-defined concept of somatization and (2) abnormal illness behavior is included in all diagnostic rubrics, but it is never conceptually defined. In the present review of the literature, we will attempt to approach the clinical issue from a different angle, by introducing the trans-diagnostic viewpoint of illness behavior and propose an alternative clinimetric classification system, based on the Diagnostic Criteria for Psychosomatic Research.

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) or § 414.509(a)(3) that the basis for payment for a new test will be gapfilling, CMS posts interim... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... Laboratory Tests § 414.509 Reconsideration of basis for and amount of payment for a new clinical diagnostic...

Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan

PubMed Central

Mikhail, Amy; Mayan, Ismail; Cundill, Bonnie; Anwar, Mohammed; Bakhtash, Sayed Habib; Mohammed, Nader; Rahman, Habib; Zekria, Rohullah; Whitty, Christopher J M; Rowland, Mark

2014-01-01

Objective To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting. Design Patient randomised trial in primary level clinics. Setting Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region). Participants 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics. Interventions Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy. Main outcome measures Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials. Results In the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001). Conclusions In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance. PMID:24948695

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

PubMed

Messacar, Kevin; Parker, Sarah K; Todd, James K; Dominguez, Samuel R

2017-03-01

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics. Copyright © 2017 American Society for Microbiology.

Discrepancy between the clinical and histopathologic diagnosis of soft tissue vascular malformations.

PubMed

Horbach, Sophie E R; Utami, Amalia M; Meijer-Jorna, Lorine B; Sillevis Smitt, J H; Spuls, Phyllis I; van der Horst, Chantal M A M; van der Wal, Allard C

2017-11-01

Soft tissue vascular malformations are generally diagnosed clinically, according to the International Society for the Study of Vascular Anomalies (ISSVA) classification. Diagnostic histopathologic examination is rarely performed. We sought to evaluate the validity of the current diagnostic workup without routinely performed diagnostic histopathology. We retrospectively determined whether there were discrepancies between clinical and histopathologic diagnoses of patients with clinically diagnosed vascular malformations undergoing therapeutic surgical resections in our center (2000-2015). Beforehand, a pathologist revised the histopathologic diagnoses according to the ISSVA classification. Clinical and histopathologic diagnoses were discrepant in 57% of 142 cases. In these cases, the pathologist indicated the diagnosis was not at all a vascular malformation (n = 24; 17%), a completely different type of vascular malformation (n = 26; 18%), or a partially different type with regard to the combination of vessel-types involved (n = 31; 22%). Possible factors associated with the discrepancies were both clinician-related (eg, diagnostic uncertainty) and pathology-related (eg, lack of immunostaining). Retrospective analysis of a subgroup of patients undergoing surgery. The large discrepancy between clinical and histopathologic diagnoses raises doubt about the validity of the current diagnostic workup for vascular malformations. Clear clinical and histopathologic diagnostic criteria might be essential for a uniform diagnosis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

PubMed Central

Graham, Stephen M.; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E.; Gale, Marianne; Gie, Robert P.; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C.; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J.; McNeeley, David F.; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R.; Swaminathan, Soumya; Wingfield, Claire

2012-01-01

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. PMID:22448023

Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer.

PubMed

Parkinson, David R; McCormack, Robert T; Keating, Susan M; Gutman, Steven I; Hamilton, Stanley R; Mansfield, Elizabeth A; Piper, Margaret A; Deverka, Patricia; Frueh, Felix W; Jessup, J Milburn; McShane, Lisa M; Tunis, Sean R; Sigman, Caroline C; Kelloff, Gary J

2014-03-15

This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

Whole exome sequencing in neurogenetic odysseys: An effective, cost- and time-saving diagnostic approach

PubMed Central

Córdoba, Marta; Rodriguez-Quiroga, Sergio Alejandro; Vega, Patricia Analía; Salinas, Valeria; Perez-Maturo, Josefina; Amartino, Hernán; Vásquez-Dusefante, Cecilia; Medina, Nancy; González-Morón, Dolores; Kauffman, Marcelo Andrés

2018-01-01

Background Diagnostic trajectories for neurogenetic disorders frequently require the use of considerable time and resources, exposing patients and families to so-called “diagnostic odysseys”. Previous studies have provided strong evidence for increased diagnostic and clinical utility of whole-exome sequencing in medical genetics. However, specific reports assessing its utility in a setting such as ours- a neurogeneticist led academic group serving in a low-income country—are rare. Objectives To assess the diagnostic yield of WES in patients suspected of having a neurogenetic condition and explore the cost-effectiveness of its implementation in a research group located in an Argentinean public hospital. Methods This is a prospective study of the clinical utility of WES in a series of 40 consecutive patients selected from a Neurogenetic Clinic of a tertiary Hospital in Argentina. We evaluated patients retrospectively for previous diagnostic trajectories. Diagnostic yield, clinical impact on management and economic diagnostic burden were evaluated. Results We demonstrated the clinical utility of Whole Exome Sequencing in our patient cohort, obtaining a diagnostic yield of 40% (95% CI, 24.8%-55.2%) among a diverse group of neurological disorders. The average age at the time of WES was 23 (range 3–70). The mean time elapsed from symptom onset to WES was 11 years (range 3–42). The mean cost of the diagnostic workup prior to WES was USD 1646 (USD 1439 to 1853), which is 60% higher than WES cost in our center. Conclusions WES for neurogenetics proved to be an effective, cost- and time-saving approach for the molecular diagnosis of this heterogeneous and complex group of patients. PMID:29389947

Efficient strategies to find diagnostic test accuracy studies in kidney journals.

PubMed

Rogerson, Thomas E; Ladhani, Maleeka; Mitchell, Ruth; Craig, Jonathan C; Webster, Angela C

2015-08-01

Nephrologists looking for quick answers to diagnostic clinical questions in MEDLINE can use a range of published search strategies or Clinical Query limits to improve the precision of their searches. We aimed to evaluate existing search strategies for finding diagnostic test accuracy studies in nephrology journals. We assessed the accuracy of 14 search strategies for retrieving diagnostic test accuracy studies from three nephrology journals indexed in MEDLINE. Two investigators hand searched the same journals to create a reference set of diagnostic test accuracy studies to compare search strategy results against. We identified 103 diagnostic test accuracy studies, accounting for 2.1% of all studies published. The most specific search strategy was the Narrow Clinical Queries limit (sensitivity: 0.20, 95% CI 0.13-0.29; specificity: 0.99, 95% CI 0.99-0.99). Using the Narrow Clinical Queries limit, a searcher would need to screen three (95% CI 2-6) articles to find one diagnostic study. The most sensitive search strategy was van der Weijden 1999 Extended (sensitivity: 0.95; 95% CI 0.89-0.98; specificity 0.55, 95% CI 0.53-0.56) but required a searcher to screen 24 (95% CI 23-26) articles to find one diagnostic study. Bachmann 2002 was the best balanced search strategy, which was sensitive (0.88, 95% CI 0.81-0.94), but also specific (0.74, 95% CI 0.73-0.75), with a number needed to screen of 15 (95% CI 14-17). Diagnostic studies are infrequently published in nephrology journals. The addition of a strategy for diagnostic studies to a subject search strategy in MEDLINE may reduce the records needed to screen while preserving adequate search sensitivity for routine clinical use. © 2015 Asian Pacific Society of Nephrology.

Measures of accuracy and performance of diagnostic tests.

PubMed

Drobatz, Kenneth J

2009-05-01

Diagnostic tests are integral to the practice of veterinary cardiology, any other specialty, and general veterinary medicine. Developing and understanding diagnostic tests is one of the cornerstones of clinical research. This manuscript describes the diagnostic test properties including sensitivity, specificity, predictive value, likelihood ratio, receiver operating characteristic curve. Review of practical book chapters and standard statistics manuscripts. Diagnostics such as sensitivity, specificity, predictive value, likelihood ratio, and receiver operating characteristic curve are described and illustrated. Basic understanding of how diagnostic tests are developed and interpreted is essential in reviewing clinical scientific papers and understanding evidence based medicine.

Reliability of Chinese medicine diagnostic variables in the examination of patients with osteoarthritis of the knee.

PubMed

Hua, Bin; Abbas, Estelle; Hayes, Alan; Ryan, Peter; Nelson, Lisa; O'Brien, Kylie

2012-11-01

Chinese medicine (CM) has its own diagnostic indicators that are used as evidence of change in a patient's condition. The majority of studies investigating efficacy of Chinese herbal medicine (CHM) have utilized biomedical diagnostic endpoints. For CM clinical diagnostic variables to be incorporated into clinical trial designs, there would need to be evidence that these diagnostic variables are reliable. Previous studies have indicated that the reliability of CM syndrome diagnosis is variable. Little information is known about where the variability stems from--the basic data collection level or the synthesis of diagnostic data, or both. No previous studies have investigated systematically the reliability of all four diagnostic methods used in the CM diagnostic process (Inquiry, Inspection, Auscultation/Olfaction, and Palpation). The objective of this study was to assess the inter-rater reliability of data collected using the four diagnostic methods of CM in Australian patients with knee osteoarthritis (OA), in order to investigate if CM variables could be used with confidence as diagnostic endpoints in a clinical trial investigating the efficacy of a CHM in treating OA. An inter-rater reliability study was conducted as a substudy of a clinical trial investigating the treatment of knee OA with Chinese herbal medicine. Two (2) experienced CM practitioners conducted a CM examination separately, within 2 hours of each other, in 40 participants. A CM assessment form was utilized to record the diagnostic data. Cohen's κ coefficient was used as a measure of the level of agreement between 2 practitioners. There was a relatively good level of agreement for Inquiry and Auscultation variables, and, in general, a low level of agreement for (visual) Inspection and Palpation variables. There was variation in the level of agreement between 2 practitioners on clinical information collected using the Four Diagnostic Methods of a CM examination. Some aspects of CM diagnosis appear to be reliable, while others are not. Based on these results, it was inappropriate to use CM diagnostic variables as diagnostic endpoints in the main study, which was an investigation of efficacy of CHM treatment of knee OA.

Evidence and diagnostic reporting in the IHE context.

PubMed

Loef, Cor; Truyen, Roel

2005-05-01

Capturing clinical observations and findings during the diagnostic imaging process is increasingly becoming a critical step in diagnostic reporting. Standards developers-notably HL7 and DICOM-are making significant progress toward standards that enable exchanging clinical observations and findings among the various information systems of the healthcare enterprise. DICOM-like the HL7 Clinical Document Architecture (CDA) -uses templates and constrained, coded vocabulary (SNOMED, LOINC, etc.). Such a representation facilitates automated software recognition of findings and observations, intrapatient comparison, correlation to norms, and outcomes research. The scope of DICOM Structured Reporting (SR) includes many findings that products routinely create in digital form (measurements, computed estimates, etc.). In the Integrating the Healthcare Enterprise (IHE) framework, two Integration Profiles are defined for clinical data capture and diagnostic reporting: Evidence Document, and Simple Image and Numeric Report. This report describes these two DICOM SR-based integration profiles in the diagnostic reporting process.

Formulations in Psychotherapy: Admission Interviews and the Conversational Construction of Diagnosis.

PubMed

Bonnin, Juan Eduardo

2017-09-01

In this article, we contribute to understanding the interactional aspects of making clinical diagnosis in mental health care. We observe that therapists, during the "problem presentation" sequence in clinical encounters, often use a specific form of diagnostic formulations to elicit more diagnostically relevant information. By doing so, they often substitute one type of verb with another, following a diagnostic hypothesis. Specifically, in interviews that arrive at a diagnosis of neurosis, therapists formulate with behavioral verbal processes; in interviews that arrive at a diagnosis of psychosis, they do so with material ones. Such formulations often prove useful to define clinical diagnoses. They can, however, also be dangerous in that they may favor the therapist's agenda over the patient's. Our analysis helps therapists not only better understand the diagnostic process but also reflect upon their own use of diagnostic formulations and become aware of the clinical effects of their interactional performance.

Measures to Improve Diagnostic Safety in Clinical Practice

PubMed Central

Singh, Hardeep; Graber, Mark L; Hofer, Timothy P

2016-01-01

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of “diagnostic safety” related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety, and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm. PMID:27768655

Assessing Clinical Reasoning (ASCLIRE): Instrument Development and Validation

ERIC Educational Resources Information Center

Kunina-Habenicht, Olga; Hautz, Wolf E.; Knigge, Michel; Spies, Claudia; Ahlers, Olaf

2015-01-01

Clinical reasoning is an essential competency in medical education. This study aimed at developing and validating a test to assess diagnostic accuracy, collected information, and diagnostic decision time in clinical reasoning. A norm-referenced computer-based test for the assessment of clinical reasoning (ASCLIRE) was developed, integrating the…

[Evidence-based cardiology: practical applications from epidemiology. III. Diagnostic capacity of a clinical test].

PubMed

Rodríguez-Escudero, Juan Pablo; López-Jiménez, Francisco; Trejo-Gutiérrez, Jorge F

2011-01-01

This article reviews different characteristics of validity in a clinical diagnostic test. In particular, we emphasize the likelihood ratio as an instrument that facilitates the use of epidemiologic concepts in clinical diagnosis.

[THE RESULTS OF CLINICAL AND PSYCHOPATHOLOGICAL AND PSYCHOLOGICAL DIAGNOSTIC INVESTIGATIONS EMPLOYEES OF FINANCIAL INSTITUTIONS WHICH WERE IDENTIFIED NEUROTIC DISORDERS].

PubMed

Solovyova, M

2014-12-01

The article presents the results of the clinical and psychopathological and psychological diagnostic, investigations mental health employees of financial institutions, description and analysis of clinical forms identified disorders.

Methodology in diagnostic laboratory test research in clinical chemistry and clinical chemistry and laboratory medicine.

PubMed

Lumbreras-Lacarra, Blanca; Ramos-Rincón, José Manuel; Hernández-Aguado, Ildefonso

2004-03-01

The application of epidemiologic principles to clinical diagnosis has been less developed than in other clinical areas. Knowledge of the main flaws affecting diagnostic laboratory test research is the first step for improving its quality. We assessed the methodologic aspects of articles on laboratory tests. We included articles that estimated indexes of diagnostic accuracy (sensitivity and specificity) and were published in Clinical Chemistry or Clinical Chemistry and Laboratory Medicine in 1996, 2001, and 2002. Clinical Chemistry has paid special attention to this field of research since 1996 by publishing recommendations, checklists, and reviews. Articles were identified through electronic searches in Medline. The strategy combined the Mesh term "sensitivity and specificity" (exploded) with the text words "specificity", "false negative", and "accuracy". We examined adherence to seven methodologic criteria used in the study by Reid et al. (JAMA1995;274:645-51) of papers published in general medical journals. Three observers evaluated each article independently. Seventy-nine articles fulfilled the inclusion criteria. The percentage of studies that satisfied each criterion improved from 1996 to 2002. Substantial improvement was observed in reporting of the statistical uncertainty of indices of diagnostic accuracy, in criteria based on clinical information from the study population (spectrum composition), and in avoidance of workup bias. Analytical reproducibility was reported frequently (68%), whereas information about indeterminate results was rarely provided. The mean number of methodologic criteria satisfied showed a statistically significant increase over the 3 years in Clinical Chemistry but not in Clinical Chemistry and Laboratory Medicine. The methodologic quality of the articles on diagnostic test research published in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine is comparable to the quality observed in the best general medical journals. The methodologic aspects that most need improvement are those linked to the clinical information of the populations studied. Editorial actions aimed to increase the quality of reporting of diagnostic studies could have a relevant positive effect, as shown by the improvement observed in Clinical Chemistry.

Diagnostic and functional structure of a high-resolution thyroid nodule clinic.

PubMed

Fernández-García, José Carlos; Mancha-Doblas, Isabel; Ortega-Jiménez, María Victoria; Ruiz-Escalante, José Francisco; Castells-Fusté, Ignasi; Tofé-Povedano, Santiago; Argüelles-Jiménez, Iñaki; Tinahones, Francisco José

2014-01-01

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Point-of-Care Diagnostics for Niche Applications

PubMed Central

Cummins, Brian M.; Ligler, Frances S.; Walker, Glenn M.

2016-01-01

Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. PMID:26837054

The biasing effect of clinical history on physical examination diagnostic accuracy.

PubMed

Sibbald, Matthew; Cavalcanti, Rodrigo B

2011-08-01

Literature on diagnostic test interpretation has shown that access to clinical history can both enhance diagnostic accuracy and increase diagnostic error. Knowledge of clinical history has also been shown to enhance the more complex cognitive task of physical examination diagnosis, possibly by enabling early hypothesis generation. However, it is unclear whether clinicians adhere to these early hypotheses in the face of unexpected physical findings, thus resulting in diagnostic error. A sample of 180 internal medicine residents received a short clinical history and conducted a cardiac physical examination on a high-fidelity simulator. Resident Doctors (Residents) were randomised to three groups based on the physical findings in the simulator. The concordant group received physical examination findings consistent with the diagnosis that was most probable based on the clinical history. Discordant groups received findings associated with plausible alternative diagnoses which either lacked expected findings (indistinct discordant) or contained unexpected findings (distinct discordant). Physical examination diagnostic accuracy and physical examination findings were analysed. Physical examination diagnostic accuracy varied significantly among groups (75 ± 44%, 2 ± 13% and 31 ± 47% in the concordant, indistinct discordant and distinct discordant groups, respectively (F(2,177)  = 53, p < 0.0001). Of the 115 Residents who were diagnostically unsuccessful, 33% adhered to their original incorrect hypotheses. Residents verbalised an average of 12 findings (interquartile range: 10-14); 58 ± 17% were correct and the percentage of correct findings was similar in all three groups (p = 0.44). Residents showed substantially decreased diagnostic accuracy when faced with discordant physical findings. The majority of trainees given discordant physical findings rejected their initial hypotheses, but were still diagnostically unsuccessful. These results suggest that overcoming the bias induced by a misleading clinical history may involve two independent steps: rejection of the incorrect initial hypothesis, and selection of the correct diagnosis. Educational strategies focused solely on prompting clinicians to re-examine their hypotheses may be insufficient to reduce diagnostic error. © Blackwell Publishing Ltd 2011.

Why patients' disruptive behaviours impair diagnostic reasoning: a randomised experiment.

PubMed

Mamede, Sílvia; Van Gog, Tamara; Schuit, Stephanie C E; Van den Berge, Kees; Van Daele, Paul L A; Bueving, Herman; Van der Zee, Tim; Van den Broek, Walter W; Van Saase, Jan L C M; Schmidt, H G

2017-01-01

Patients who display disruptive behaviours in the clinical encounter (the so-called 'difficult patients') may negatively affect doctors' diagnostic reasoning, thereby causing diagnostic errors. The present study aimed at investigating the mechanisms underlying the negative influence of difficult patients' behaviours on doctors' diagnostic performance. A randomised experiment with 74 internal medicine residents. Doctors diagnosed eight written clinical vignettes that were exactly the same except for the patients' behaviours (either difficult or neutral). Each participant diagnosed half of the vignettes in a difficult patient version and the other half in a neutral version in a counterbalanced design. After diagnosing each vignette, participants were asked to recall the patient's clinical findings and behaviours. Main measurements were: diagnostic accuracy scores; time spent on diagnosis, and amount of information recalled from patients' clinical findings and behaviours. Mean diagnostic accuracy scores (range 0-1) were significantly lower for difficult than neutral patients' vignettes (0.41 vs 0.51; p<0.01). Time spent on diagnosing was similar. Participants recalled fewer clinical findings (mean=29.82% vs mean=32.52%; p<0.001) and more behaviours (mean=25.51% vs mean=17.89%; p<0.001) from difficult than from neutral patients. Difficult patients' behaviours induce doctors to make diagnostic errors, apparently because doctors spend part of their mental resources on dealing with the difficult patients' behaviours, impeding adequate processing of clinical findings. Efforts should be made to increase doctors' awareness of the potential negative influence of difficult patients' behaviours on diagnostic decisions and their ability to counteract such influence. 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/.

A computational framework for converting textual clinical diagnostic criteria into the quality data model.

PubMed

Hong, Na; Li, Dingcheng; Yu, Yue; Xiu, Qiongying; Liu, Hongfang; Jiang, Guoqian

2016-10-01

Constructing standard and computable clinical diagnostic criteria is an important but challenging research field in the clinical informatics community. The Quality Data Model (QDM) is emerging as a promising information model for standardizing clinical diagnostic criteria. To develop and evaluate automated methods for converting textual clinical diagnostic criteria in a structured format using QDM. We used a clinical Natural Language Processing (NLP) tool known as cTAKES to detect sentences and annotate events in diagnostic criteria. We developed a rule-based approach for assigning the QDM datatype(s) to an individual criterion, whereas we invoked a machine learning algorithm based on the Conditional Random Fields (CRFs) for annotating attributes belonging to each particular QDM datatype. We manually developed an annotated corpus as the gold standard and used standard measures (precision, recall and f-measure) for the performance evaluation. We harvested 267 individual criteria with the datatypes of Symptom and Laboratory Test from 63 textual diagnostic criteria. We manually annotated attributes and values in 142 individual Laboratory Test criteria. The average performance of our rule-based approach was 0.84 of precision, 0.86 of recall, and 0.85 of f-measure; the performance of CRFs-based classification was 0.95 of precision, 0.88 of recall and 0.91 of f-measure. We also implemented a web-based tool that automatically translates textual Laboratory Test criteria into the QDM XML template format. The results indicated that our approaches leveraging cTAKES and CRFs are effective in facilitating diagnostic criteria annotation and classification. Our NLP-based computational framework is a feasible and useful solution in developing diagnostic criteria representation and computerization. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic criteria, severity classification and guidelines of localized scleroderma.

PubMed

Asano, Yoshihide; Fujimoto, Manabu; Ishikawa, Osamu; Sato, Shinichi; Jinnin, Masatoshi; Takehara, Kazuhiko; Hasegawa, Minoru; Yamamoto, Toshiyuki; Ihn, Hironobu

2018-04-23

We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma. © 2018 Japanese Dermatological Association.

Evaluating the accessibility and utility of HIV-related point-of-care diagnostics for maternal health in rural South Africa: a study protocol

PubMed Central

Mashamba-Thompson, T P; Drain, P K; Sartorius, B

2016-01-01

Introduction Poor healthcare access is a major barrier to receiving antenatal care and a cause of high maternal mortality in South Africa (SA). ‘Point-of-care’ (POC) diagnostics is a powerful emerging healthcare approach to improve healthcare access. This study focuses on evaluating the accessibility and utility of POC diagnostics for maternal health in rural SA primary healthcare (PHC) clinics in order to generate a model framework of implementation of POC diagnostics in rural South African clinics. Method and analyses We will use several research methods, including a systematic review, quasi-experiments, survey, key informant interviews and audits. We will conduct a systematic review and experimental study to determine the impact of POC diagnostics on maternal health. We will perform a cross-sectional case study of 100 randomly selected rural primary healthcare clinics in KwaZulu-Natal to measure the context and patterns of POC diagnostics access and usage by maternal health providers and patients. We will conduct interviews with relevant key stakeholders to determine the reasons for POC deficiencies regarding accessibility and utility of HIV-related POC diagnostics for maternal health. We will also conduct a vertical audit to investigate all the quality aspects of POC diagnostic services including diagnostic accuracy in a select number of clinics. On the basis of information gathered, we will propose a model framework for improved implementation of POC diagnostics in rural South African public healthcare clinics. Statistical (Stata-13) and thematic (NVIVO) data analysis will be used in this study. Ethics and dissemination The study protocol was approved by the Ethics Committee of the University of KwaZulu-Natal (BE 484/14) and the KwaZulu-Natal Department of Health based on the Helsinki Declaration (HRKM 40/15). Findings of this study will be disseminated electronically and in print. They will be presented to conferences related to HIV/AIDS, diagnostics, maternal health and strengthening of health systems. PMID:27354074

Oral manifestations of hematologic and nutritional diseases.

PubMed

Schlosser, Bethanee J; Pirigyi, Megan; Mirowski, Ginat W

2011-02-01

Oral manifestations of hematologic and nutritional deficiencies can affect the mucous membranes, teeth, periodontal tissues, salivary glands, and perioral skin. This article reviews common oral manifestations of hematologic conditions starting with disorders of the white blood cells including cyclic hematopoiesis (cyclic neutropenia), leukemias, lymphomas, plasma cell dyscrasias, and mast cell disorders; this is followed by a discussion of the impact of red blood cell disorders including anemias and less common red blood cell dyscrasias (sickle cell disease, hemochromatosis, and congenital erythropoietic porphyria) as well as thrombocytopenia. Several nutritional deficiencies exhibit oral manifestations. The authors specifically discuss the impact of water-soluble vitamins (B2, B3, B6, B9, B12, and C), fat-soluble vitamins (A, D, and K) and the eating disorders anorexia nervosa and bulimia nervosa on the oral mucosa. Copyright © 2011 Elsevier Inc. All rights reserved.

Parkinson's Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism.

PubMed

van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Meijer, Frederick J A; Verbeek, Marcel M; Bloem, Bastiaan R

2018-05-16

Differentiation of Parkinson's disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers. Patients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years' follow-up will serve as the "gold standard" reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of individuals that are correctly diagnosed with PD or AP. This study will yield new insights into the diagnostic value of clinical evaluation by a movement disorder specialist, brain MRI and CSF analysis in discriminating PD from AP in early disease stages. The outcome has the potential to help clinicians in choosing the optimal diagnostic strategy for patients with an uncertain clinical diagnosis. NCT01249768, registered November 26 2010.

Introducing First-Year Medical Students to Early Diagnostic Hypotheses

ERIC Educational Resources Information Center

Taylor, P. J.; And Others

1978-01-01

A method of instruction in gynecology is described that encouraged the formulation of early diagnostic hypotheses, an important part of clinical problem-solving. Students were given a set of clinical clues to help them make broad diagnostic hypotheses. Student ability, results, and student perceptions of the course are provided. (Author/LBH)

Diagnoses and Presenting Symptoms in an Infant Psychiatry Clinic: Comparison of Two Diagnostic Systems.

ERIC Educational Resources Information Center

Frankel, Karen A.; Boyum, Lisa A.; Harmon, Robert J.

2004-01-01

Objective: To present data from a general infant psychiatry clinic, including range and frequency of presenting symptoms, relationship between symptoms and diagnoses, and comparison of two diagnostic systems, DSM-IV and Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0-3). Method: A…

Becoming a teacher of clinical reasoning.

PubMed

Trowbridge, Robert L; Olson, Andrew P J

2018-03-28

Diagnostic reasoning is one of the most challenging and rewarding aspects of clinical practice. As a result, facility in teaching diagnostic reasoning is a core necessity for all medical educators. Clinician educators' limited understanding of the diagnostic process and how expertise is developed may result in lost opportunities in nurturing the diagnostic abilities of themselves and their learners. In this perspective, the authors describe their journeys as clinician educators searching for a coherent means of teaching diagnostic reasoning. They discuss the initial appeal and immediate applicability of dual process theory and cognitive biases to their own clinical experiences and those of their trainees, followed by the eventual and somewhat belated recognition of the importance of context specificity. They conclude that there are no quick fixes in guiding learners to expertise of diagnostic reasoning, but rather the development of these abilities is best viewed as a long, somewhat frustrating, but always interesting journey. The role of the teacher of clinical reasoning is to guide the learners on this journey, recognizing true mastery may not be attained, but should remain a goal for teacher and learner alike.

Current and proposed molecular diagnostics in a genitourinary service line laboratory at a tertiary clinical institution.

PubMed

Udager, Aaron M; Alva, Ajjai; Mehra, Rohit

2014-01-01

The idea that detailed knowledge of molecular oncogenesis will drive diagnostic, prognostic, and therapeutic clinical decision making in an increasingly multidisciplinary practice of oncologic care has been anticipated for many years. With the recent rapid advancement in our understanding of the molecular underpinnings of genitourinary malignancies, this concept is now starting to take shape in the fields of prostate, kidney, bladder, testicular, and penile cancer. Such breakthroughs necessitate the development of robust clinical-grade assays that can be quickly made available for patients to facilitate diagnosis in challenging cases, risk-stratify patients for subsequent clinical management, select the appropriate targeted therapy from among increasingly diverse and numerous options, and enroll patients in advanced clinical trials. This rapid translation of basic and clinical cancer research requires a streamlined, multidisciplinary approach to clinical assay development, termed here the molecular diagnostics service line laboratory. In this review, we summarize the current state and explore the future of molecular diagnostics in genitourinary oncology to conceptualize a genitourinary service line laboratory at a tertiary clinical institution.

Evaluating Malaria Prevalence Using Clinical Diagnosis Compared with Microscopy and Rapid Diagnostic Tests in a Tertiary Healthcare Facility in Rivers State, Nigeria.

PubMed

Wogu, M N; Nduka, F O

2018-01-01

The World Health Organization's policy on laboratory test of all suspected malaria cases before treatment has not yielded significant effects in several rural areas of Sub-Saharan Africa due to inadequate diagnostic infrastructure, leading to high morbidity and mortality rates. A cross-sectional randomized study was conducted to evaluate the validity of clinical malaria diagnosis through comparison with microscopy and rapid diagnostic test kits (RDTs) using 1000 consenting outpatients of a tertiary hospital in Nigeria. Physicians conducted clinical diagnosis, and blood samples were collected through venous procedure and analyzed for malaria parasites using Giemsa microscopy and RDT kits. Microscopy was considered the diagnostic "gold standard" and all data obtained were statistically analyzed using Chi-square test with a P value <0.05 considered significant. Malaria prevalence values of 20.1%, 43.1%, and 29.7% were obtained for clinical diagnosis, microscopy, and RDTs, respectively ( P < 0.05). Values of 47.2%, 95.9%, and 77.8% were obtained for sensitivity, specificity, and diagnostic accuracy, respectively, in clinical diagnosis, while RDTs had sensitivity, specificity, and diagnostic accuracy values of 73.7%, 97.3%, and 88.3%, respectively, when compared to microscopy ( P < 0.05). Clinical diagnosed malaria cases should be confirmed with a parasite-based laboratory diagnosis and more qualitative research is needed to explore why clinicians still use clinical diagnosis despite reported cases of its ineffectiveness.

The rare and undiagnosed diseases diagnostic service - application of massively parallel sequencing in a state-wide clinical service.

PubMed

Baynam, Gareth; Pachter, Nicholas; McKenzie, Fiona; Townshend, Sharon; Slee, Jennie; Kiraly-Borri, Cathy; Vasudevan, Anand; Hawkins, Anne; Broley, Stephanie; Schofield, Lyn; Verhoef, Hedwig; Walker, Caroline E; Molster, Caron; Blackwell, Jenefer M; Jamieson, Sarra; Tang, Dave; Lassmann, Timo; Mina, Kym; Beilby, John; Davis, Mark; Laing, Nigel; Murphy, Lesley; Weeramanthri, Tarun; Dawkins, Hugh; Goldblatt, Jack

2016-06-11

The Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) refers to a genomic diagnostic platform operating within the Western Australian Government clinical services delivered through Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for 28 years and it serves a population of 2.5 million people across a geographical area of 2.5milion Km(2). Within this context, GSWA has established a clinically integrated genomic diagnostic platform in partnership with other public health system managers and service providers, including but not limited to the Office of Population Health Genomics, Diagnostic Genomics (PathWest Laboratories) and with executive level support from the Department of Health. Herein we describe report presents the components of this service that are most relevant to the heterogeneity of paediatric clinical genetic care. Briefly the platform : i) offers multiple options including non-genetic testing; monogenic and genomic (targeted in silico filtered and whole exome) analysis; and matchmaking; ii) is delivered in a patient-centric manner that is resonant with the patient journey, it has multiple points for entry, exit and re-entry to allow people access to information they can use, when they want to receive it; iii) is synchronous with precision phenotyping methods; iv) captures new knowledge, including multiple expert review; v) is integrated with current translational genomic research activities and best practice; and vi) is designed for flexibility for interactive generation of, and integration with, clinical research for diagnostics, community engagement, policy and models of care. The RUDDS has been established as part of routine clinical genetic services and is thus sustainable, equitably managed and seeks to translate new knowledge into efficient diagnostics and improved health for the whole community.

78 FR 20112 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

...-related information. The respondents would be clinical laboratory supervisors, nurses, and other.../60 300 Supervisors. Influenza Diagnostic Test Practices in Clinical Laboratories. Nurses Survey of... this notice. Proposed Project Survey of Rapid Influenza Diagnostic Test (RIDT) Practices in Clinical...

The diagnostic management of upper extremity deep vein thrombosis: A review of the literature.

PubMed

Kraaijpoel, Noémie; van Es, Nick; Porreca, Ettore; Büller, Harry R; Di Nisio, Marcello

2017-08-01

Upper extremity deep vein thrombosis (UEDVT) accounts for 4% to 10% of all cases of deep vein thrombosis. UEDVT may present with localized pain, erythema, and swelling of the arm, but may also be detected incidentally by diagnostic imaging tests performed for other reasons. Prompt and accurate diagnosis is crucial to prevent pulmonary embolism and long-term complications as the post-thrombotic syndrome of the arm. Unlike the diagnostic management of deep vein thrombosis (DVT) of the lower extremities, which is well established, the work-up of patients with clinically suspected UEDVT remains uncertain with limited evidence from studies of small size and poor methodological quality. Currently, only one prospective study evaluated the use of an algorithm, similar to the one used for DVT of the lower extremities, for the diagnostic workup of clinically suspected UEDVT. The algorithm combined clinical probability assessment, D-dimer testing and ultrasonography and appeared to safely and effectively exclude UEDVT. However, before recommending its use in routine clinical practice, external validation of this strategy and improvements of the efficiency are needed, especially in high-risk subgroups in whom the performance of the algorithm appeared to be suboptimal, such as hospitalized or cancer patients. In this review, we critically assess the accuracy and efficacy of current diagnostic tools and provide clinical guidance for the diagnostic management of clinically suspected UEDVT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical epidemiology.

PubMed

Martin, S W; Bonnett, B

1987-06-01

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

Diagnostic criteria, severity classification and guidelines of systemic sclerosis.

PubMed

Asano, Yoshihide; Jinnin, Masatoshi; Kawaguchi, Yasushi; Kuwana, Masataka; Goto, Daisuke; Sato, Shinichi; Takehara, Kazuhiko; Hatano, Masaru; Fujimoto, Manabu; Mugii, Naoki; Ihn, Hironobu

2018-06-01

Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. © 2018 Japanese Dermatological Association.

Biochemical Characterization of Porphobilinogen Deaminase–Deficient Mice During Phenobarbital Induction of Heme Synthesis and the Effect of Enzyme Replacement

PubMed Central

Johansson, Annika; Möller, Christer; Fogh, Jens; Harper, Pauline

2003-01-01

Acute intermittent porphyria (AIP) is a genetic disorder caused by a deficiency of porphobilinogen deaminase (PBGD), the 3rd enzyme in heme synthesis. It is clinically characterized by acute attacks of neuropsychiatric symptoms and biochemically by increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA). A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD). After 4 d of phenobarbital administration, high levels of PBG and ALA were found in liver, kidney, plasma, and urine of the PBGD-deficient mice. The administration of rhPBGD intravenously or subcutaneously after a 4-d phenobarbital induction was shown to lower the PBG level in plasma in a dose-dependent manner with maximal effect seen after 30 min and 2 h, respectively. Injection of rhPBGD subcutaneously twice daily during a 4-d phenobarbital induction reduced urinary PBG excretion to 25% of the levels found in PBGD-deficient mice administered with only phenobarbital. This study points to the liver as the main producer of PBG and ALA in the phenobarbital-induced PBGD-deficient mice and demonstrates efficient removal of accumulated PBG in plasma and urine by enzyme-replacement therapy. PMID:15208740

Clinicopathological characteristics of xeroderma pigmentosum associated with keratoacanthoma: a case report and literature review.

PubMed

Zheng, Jin-Feng; Mo, Hai-Ying; Wang, Zhen-Zheng

2014-01-01

To investigate the clinicopathological characteristics, diagnosis and differential diagnosis, and treatment of xeroderma pigmentosum associated with keratoacanthoma in an infant. The clinical manifestations of xeroderma pigmentosum associated with keratoacanthoma were assessed in an 18-month old boy. The morphological and histological features of the lesions were examined by light microscopy. An 18-month old boy was admitted with unequal size, irregularly shaped brown spots, patches and depigmentation spots on his face. A well-circumscribed hemispherical mass measuring 3 cm × 3 cm with smooth surface and brown patches was observed beneath his left lower eyelid. Light microscopic examination of the skin lesions revealed epidermal hyperkeratosis, chronic inflammatory infiltration of the superficial dermal layer, and increases in melanocytes and melanin in the basal layer. Scanning microscopy showed that the mass beneath the left lower eyelid was cup-shaped, consisting of proliferating squamous cells with a central keratin plug. The squamous epithelium was acanthotic with hypergranulosis. The adjacent epidermis formed exophytic projections resulting in a silhouette likened to lips. An associated inflammatory reaction was observed within the stroma surrounding the mass. The patient was treated with a combination of antioxidant drugs, keeping the child from light and surgical excision of the mass. No recurrence has been observed. Xeroderma pigmentosum of infancy is a rare disease, and association with keratoacanthoma is even rarer. This condition should be considered in the differential diagnosis of freckles, Rothmund-Thomson syndrome and porphyria.

[Diagnostic test scale SI5: Assessment of sacroiliac joint dysfunction].

PubMed

Acevedo González, Juan C; Quintero Oliveros, Silvia

2015-01-01

Sacroiliac joint dysfunction is a known cause of low back pain. We think that a diagnostic score scale (SI5) may be performed to assess diagnostic utility of clinical signs of sacroiliac joint dysfunction. The primary aim of the present study was to conduct the pilot study of our new diagnostic score scale, the SI5, for sacroiliac joint syndrome. We reviewed the literature on clinical characteristics, diagnostic tests and imaging most commonly used in diagnosing sacroiliac joint dysfunction. Our group evaluated the diagnostic utility of these aspects and we used those considered most representative to develop the SI5 diagnostic scale. The SI5 scale was applied to 22 patients with low back pain; afterwards, the standard test for diagnosing this pathology (selective blockage of the SI joint) was also performed on these patients. The sensitivity and specificity for each sign were also assessed and the diagnostic scale called SI5 was then proposed, based on these data. The most sensitive clinical tests for diagnosing SI joint dysfunction were 2 patient-reported clinical characteristics, the Laguerre Test, sacroiliac rocking test and Yeomans test (greater than 80% sensitivity). The tests with greatest diagnostic specificity (>80%) were the Lewitt test, Piedallu test and Gillet test. The proposed SI5 test score scale showed sensitivity of 73% and specificity of 71%. Sacroiliac joint syndrome has been shown to produce low back pain frequently; however, the diagnostic value of examination tests for sacroiliac joint pain has been questioned by other authors. The pilot study on the SI5 diagnostic score scale showed good sensitivity and specificity. However, the process of statistical validation of the SI5 needs to be continued. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Towards a proposal for a universal diagnostic definition of protein-losing enteropathy in Fontan patients: a systematic review.

PubMed

Udink Ten Cate, Floris Ea; Hannes, Tobias; Germund, Ingo; Khalil, Markus; Huntgeburth, Michael; Apitz, Christian; Brockmeier, Konrad; Sreeram, Narayanswami

2016-07-15

A standardised diagnostic definition of protein-losing enteropathy (PLE) in Fontan patients serves both patient care and research. The present study determined whether a diagnostic definition of PLE was routinely used in published clinical Fontan studies, and to identify potentially relevant diagnostic criteria for composing a uniform PLE definition. A systematic review was conducted in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Published clinical Fontan studies that were written in English and included at least four patients with PLE were selected. PLE definitions were quantitatively analysed using a lateral thinking tool in which definitions were fractionated into constituent pieces of information (building blocks or diagnostic criteria). We identified 364 papers. In the final analysis, data from 62 published articles were extracted. A diagnostic definition of PLE was used in only 27/62 (43.5%) of selected studies, and definitions were very heterogeneous. We identified eight major diagnostic criteria. Hypoalbuminaemia (n=23 studies, 85.2%), clinical presentation (n=18, 66.7%), documentation of enteric protein loss (n=16, 59.3%) and exclusion of other causes of hypoproteinaemia (n=17, 63.0%), were the most frequently used diagnostic criteria. Most studies used three diagnostic variables (n=13/27, 48.1%). Cut-off values for laboratory parameters (serum albumin, protein or faecal α-1-antitrypsin) were frequently incorporated in the PLE definition (n=16, 59.3%). Establishment of a universally accepted PLE definition for routine use in clinical research and daily practice is required. The diagnostic criteria may help constitute a diagnostic PLE definition. 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/

Meta-Review of CSF Core Biomarkers in Alzheimer’s Disease: The State-of-the-Art after the New Revised Diagnostic Criteria

PubMed Central

Ferreira, Daniel; Perestelo-Pérez, Lilisbeth; Westman, Eric; Wahlund, Lars-Olof; Sarría, Antonio; Serrano-Aguilar, Pedro

2014-01-01

Background: Current research criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers into the diagnostic algorithm. However, spreading their use to the clinical routine is still questionable. Objective: To provide an updated, systematic and critical review on the diagnostic utility of the CSF core biomarkers for AD. Data sources: MEDLINE, PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane Library, and CRD. Eligibility criteria: (1a) Systematic reviews with meta-analysis; (1b) Primary studies published after the new revised diagnostic criteria; (2) Evaluation of the diagnostic performance of at least one CSF core biomarker. Results: The diagnostic performance of CSF biomarkers is generally satisfactory. They are optimal for discriminating AD patients from healthy controls. Their combination may also be suitable for mild cognitive impairment (MCI) prognosis. However, CSF biomarkers fail to distinguish AD from other forms of dementia. Limitations: (1) Use of clinical diagnosis as standard instead of pathological postmortem confirmation; (2) variability of methodological aspects; (3) insufficiently long follow-up periods in MCI studies; and (4) lower diagnostic accuracy in primary care compared with memory clinics. Conclusion: Additional work needs to be done to validate the application of CSF core biomarkers as they are proposed in the new revised diagnostic criteria. The use of CSF core biomarkers in clinical routine is more likely if these limitations are overcome. Early diagnosis is going to be of utmost importance when effective pharmacological treatment will be available and the CSF core biomarkers can also be implemented in clinical trials for drug development. PMID:24715863

Malaria Diagnostics in Clinical Trials

PubMed Central

Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

2013-01-01

Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

Point-of-care diagnostics for niche applications.

PubMed

Cummins, Brian M; Ligler, Frances S; Walker, Glenn M

2016-01-01

Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

PubMed

La Cesa, S; Tamburin, S; Tugnoli, V; Sandrini, G; Paolucci, S; Lacerenza, M; Marchettini, P; Cruccu, G; Truini, A

2015-12-01

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

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 simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the "herald wave" of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy. Based on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (> or =2 x n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results. The accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing. The diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic. Copyright 2010 Elsevier Inc. All rights reserved.

A Prospective, Blinded, Multicenter Clinical Trial to Compare the Efficacy, Accuracy, and Safety of In-Office Diagnostic Arthroscopy With Magnetic Resonance Imaging and Surgical Diagnostic Arthroscopy.

PubMed

Gill, Thomas J; Safran, Marc; Mandelbaum, Bert; Huber, Bryan; Gambardella, Ralph; Xerogeanes, John

2018-05-24

The purpose of this study was to compare the efficacy, accuracy, and safety of in-office diagnostic arthroscopy with magnetic resonance imaging (MRI) and surgical diagnostic arthroscopy. A prospective, blinded, multicenter, clinical trial was performed on 110 patients, ages 18 to 75 years, who presented with knee pain. The study period was April 2012 to April 2013. Each patient underwent a physical examination, an MRI, in-office diagnostic imaging, and a diagnostic arthroscopic examination in the operating room. The attending physician completed clinical report forms comparing the in-office arthroscopic examination and surgical diagnostic arthroscopy findings on each patient. Two blinded experts, unaffiliated with the clinical care of the study's subjects, reviewed the in-office arthroscopic images and MRI images using the surgical diagnostic arthroscopy images as the "control" group comparison. Patients were consecutive, and no patients were excluded from the study. In this study, the accuracy, sensitivity, and specificity of in-office arthroscopy was equivalent to surgical diagnostic arthroscopy and more accurate than MRI. When comparing in-office arthroscopy with surgical diagnostic arthroscopy, all kappa statistics were between 0.766 and 0.902. For MRI compared with surgical diagnostic arthroscopy, kappa values ranged from a low of 0.130 (considered "slight" agreement) to a high of 0.535 (considered "moderate" agreement). The comparison of MRI to in-office arthroscopy showed very similar results as the comparison of MRI with surgical diagnostic arthroscopy, ranging from a low kappa of 0.112 (slight agreement) to a high of 0.546 (moderate agreement). There were no patient-related or device-related complications related to the use of in-office arthroscopy. Needle-based diagnostic imaging that can be used in the office setting is statistically equivalent to surgical diagnostic arthroscopy with regard to the diagnosis of intra-articular, nonligamentous knee joint pathology. In-office diagnostic imaging can provide a more detailed and accurate diagnostic assessment of intra-articular knee pathology than MRI. Based on the study results, in-office diagnostic imaging provides a safe, accurate, real-time, minimally invasive diagnostic modality to evaluate intra-articular pathology without the need for surgical diagnostic arthroscopy or high-cost imaging. Level II, comparative prospective trial. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

WE-G-217BCD-04: Diagnostic Image Quality Evaluation of a Dedicated Extremity Cone- Beam CT Scanner: Pre-Clinical Studies and First Clinical Results.

PubMed

Muhit, A; Zbijewski, W; Stayman, J; Thawait, G; Yorkston, J; Foos, D; Packard, N; Yang, D; Senn, R; Carrino, J; Siewerdsen, J

2012-06-01

To assess the diagnostic performance of a prototype cone-beam CT (CBCT) scanner developed for musculoskeletal extremity imaging. Studies involved controlled observer studies conducted subsequent to rigorous technical assessment as well as patient images from the first clinical trial in imaging the hand and knee. Performance assessment included: 1.) rigorous technical assessment; 2.) controlled observer studies using CBCT images of cadaveric specimens; and 3.) first clinical images. Technical assessment included measurement of spatial resolution (MTF), constrast, and noise (SDNR) versus kVp and dose using standard CT phantoms. Diagnostic performance in comparison to multi- detector CT (MDCT) was assessed in controlled observer studies involving 12 cadaveric hands and knees scanned with and without abnormality (fracture). Observer studies involved five radiologists rating pertinent diagnostics tasks in 9-point preference and 10-point diagnostic satisfaction scales. Finally, the first clinical images from an ongoing pilot study were assessed in terms of diagnostic utility in disease assessment and overall workflow in patient setup. Quantitative assessment demonstrated sub-mm spatial resolution (MTF exceeding 10% out to 15-20 cm-1) and SDNR sufficient for relevant soft-tissue visualization tasks at dose <10 mGy. Observer studies confirmed optimal acquisition techniques and demonstrated superior utility of combined soft-tissue visualization and isotropic spatial resolution in diagnostic tasks. Images from the patient trial demonstrate exquisite contrast and detail and the ability to detect tissue impingement in weight-bearing exams. The prototype CBCT scanner provides isotropic spatial resolution superior to standard-protocol MDCT with soft-tissue visibility sufficient for a broad range of diagnostic tasks in musculoskeletal radiology. Dosimetry and workflow were advantageous in comparison to whole-body MDCT. Multi-mode and weight-bearing capabilities add valuable functionality. An ongoing clinical study further assesses diagnostic utility and defines the role of such technology in the diagnostic arsenal. - Research Grant, Carestream Health - Research Grant, National Institutes of Health 2R01-CA-112163. © 2012 American Association of Physicists in Medicine.

Use of clinical prediction rules and D-dimer tests in the diagnostic management of pregnant patients with suspected acute pulmonary embolism.

PubMed

Van der Pol, L M; Mairuhu, A T A; Tromeur, C; Couturaud, F; Huisman, M V; Klok, F A

2017-03-01

Because pregnant women have an increased risk of venous thromboembolism (VTE) and at the same time normal pregnancy is associated with symptoms, mimicking those present in the setting of acute pulmonary embolism (PE), the latter diagnosis is frequently suspected in this patient category. Since imaging tests expose both mother and foetus to ionizing radiation, the ability to rule out PE based on non-radiological diagnostic tests is of paramount importance. However, clinical decision rules have only been scarcely evaluated in the pregnant population with suspected PE, while D-dimer levels lose diagnostic accuracy due to a physiological increase during normal pregnancy. Consequently, clinical guidelines provide contradicting and weak recommendations on this subject and the optimal diagnostic strategy remains highly debated. With this systematic review, we aimed to summarize current evidence on the safety and efficacy of clinical decision rules and biomarkers used in the diagnostic management of suspected acute PE in pregnant patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Primer on Receiver Operating Characteristic Analysis and Diagnostic Efficiency Statistics for Pediatric Psychology: We Are Ready to ROC

PubMed Central

2014-01-01

Objective To offer a practical demonstration of receiver operating characteristic (ROC) analyses, diagnostic efficiency statistics, and their application to clinical decision making using a popular parent checklist to assess for potential mood disorder. Method Secondary analyses of data from 589 families seeking outpatient mental health services, completing the Child Behavior Checklist and semi-structured diagnostic interviews. Results Internalizing Problems raw scores discriminated mood disorders significantly better than did age- and gender-normed T scores, or an Affective Problems score. Internalizing scores <8 had a diagnostic likelihood ratio <0.3, and scores >30 had a diagnostic likelihood ratio of 7.4. Conclusions This study illustrates a series of steps in defining a clinical problem, operationalizing it, selecting a valid study design, and using ROC analyses to generate statistics that support clinical decisions. The ROC framework offers important advantages for clinical interpretation. Appendices include sample scripts using SPSS and R to check assumptions and conduct ROC analyses. PMID:23965298

A primer on receiver operating characteristic analysis and diagnostic efficiency statistics for pediatric psychology: we are ready to ROC.

PubMed

Youngstrom, Eric A

2014-03-01

To offer a practical demonstration of receiver operating characteristic (ROC) analyses, diagnostic efficiency statistics, and their application to clinical decision making using a popular parent checklist to assess for potential mood disorder. Secondary analyses of data from 589 families seeking outpatient mental health services, completing the Child Behavior Checklist and semi-structured diagnostic interviews. Internalizing Problems raw scores discriminated mood disorders significantly better than did age- and gender-normed T scores, or an Affective Problems score. Internalizing scores <8 had a diagnostic likelihood ratio <0.3, and scores >30 had a diagnostic likelihood ratio of 7.4. This study illustrates a series of steps in defining a clinical problem, operationalizing it, selecting a valid study design, and using ROC analyses to generate statistics that support clinical decisions. The ROC framework offers important advantages for clinical interpretation. Appendices include sample scripts using SPSS and R to check assumptions and conduct ROC analyses.

ADHD Diagnosis: As Simple As Administering a Questionnaire or a Complex Diagnostic Process?

PubMed

Parker, Ashton; Corkum, Penny

2016-06-01

The present study investigated the validity of using the Conners' Teacher and Parent Rating Scales (CTRS/CPRS) or semistructured diagnostic interviews (Parent Interview for Child Symptoms and Teacher Telephone Interview) to predict a best-practices clinical diagnosis of ADHD. A total of 279 children received a clinical diagnosis based on a best-practices comprehensive assessment (including diagnostic parent and teacher interviews, collection of historical information, rating scales, classroom observations, and a psychoeducational assessment) at a specialty ADHD Clinic in Truro, Nova Scotia, Canada. Sensitivity and specificity with clinical diagnosis were determined for the ratings scales and diagnostic interviews. Sensitivity and specificity values were high for the diagnostic interviews (91.8% and 70.7%, respectively). However, while sensitivity of the CTRS/CPRS was relatively high (83.5%), specificity was poor (35.7%). The low specificity of the CPRS/CTRS is not sufficient to be used alone to diagnose ADHD. (J. of Att. Dis. 2016; 20(6) 478-486). © The Author(s) 2013.

Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana.

PubMed

Ansah, Evelyn K; Narh-Bana, Solomon; Epokor, Michael; Akanpigbiam, Samson; Quartey, Alberta Amu; Gyapong, John; Whitty, Christopher J M

2010-03-05

To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical (peripheral) settings that rely on clinical diagnosis. Randomised, controlled, open label clinical trial. Four clinics in the rural Dangme West district of southern Ghana, one in which microscopy is used for diagnosis of malaria ("microscopy setting") and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms ("clinical setting"). Patients with suspected malaria. Interventions Patients were randomly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic (microscopy or clinical diagnosis). A blood sample for a research microscopy slide was taken for all patients. The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria. The major secondary outcomes were the correct prescription of antimalarials, the impact of test results on antibiotic prescription, and the correct prescription of antimalarials in children under 5 years. Of the 9236 patients screened, 3452 were randomised in the clinical setting and 3811 in the microscopy setting. Follow-up to 28 days was 97.6% (7088/7263). In the microscopy setting, 722 (51.6%) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 (55.0%) of the 1389 patients in the microscopy arm (adjusted odds ratio 0.87, 95% CI 0.71 to 1.1; P=0.16). In the clinical setting, 578 (53.9%) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 (90.1%) of the 1090 patients with negative slides in the clinical diagnosis arm (odds ratio 0.12, 95% CI 0.04 to 0.38; P=0.001). The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting, in both children and adults. There were no deaths in children under 5 years at 28 days follow-up in either arm. Where microscopy already exists, introducing rapid diagnostic tests had limited impact on prescriber behaviour. In settings where microscopy was not available, however, using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials, without any evidence of clinical harm, and to better targeting of antibiotics. Trial registration ClinicalTrials.gov NCT00493922.

Accuracy of clinical tests in the diagnosis of anterior cruciate ligament injury: a systematic review

PubMed Central

2014-01-01

Background Numerous clinical tests are used in the diagnosis of anterior cruciate ligament (ACL) injury but their accuracy is unclear. The purpose of this study is to evaluate the diagnostic accuracy of clinical tests for the diagnosis of ACL injury. Methods Study Design: Systematic review. The review protocol was registered through PROSPERO (CRD42012002069). Electronic databases (PubMed, MEDLINE, EMBASE, CINAHL) were searched up to 19th of June 2013 to identify diagnostic studies comparing the accuracy of clinical tests for ACL injury to an acceptable reference standard (arthroscopy, arthrotomy, or MRI). Risk of bias was appraised using the QUADAS-2 checklist. Index test accuracy was evaluated using a descriptive analysis of paired likelihood ratios and displayed as forest plots. Results A total of 285 full-text articles were assessed for eligibility, from which 14 studies were included in this review. Included studies were deemed to be clinically and statistically heterogeneous, so a meta-analysis was not performed. Nine clinical tests from the history (popping sound at time of injury, giving way, effusion, pain, ability to continue activity) and four from physical examination (anterior draw test, Lachman’s test, prone Lachman’s test and pivot shift test) were investigated for diagnostic accuracy. Inspection of positive and negative likelihood ratios indicated that none of the individual tests provide useful diagnostic information in a clinical setting. Most studies were at risk of bias and reported imprecise estimates of diagnostic accuracy. Conclusion Despite being widely used and accepted in clinical practice, the results of individual history items or physical tests do not meaningfully change the probability of ACL injury. In contrast combinations of tests have higher diagnostic accuracy; however the most accurate combination of clinical tests remains an area for future research. Clinical relevance Clinicians should be aware of the limitations associated with the use of clinical tests for diagnosis of ACL injury. PMID:25187877

High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders.

PubMed

Yavarna, Tarunashree; Al-Dewik, Nader; Al-Mureikhi, Mariam; Ali, Rehab; Al-Mesaifri, Fatma; Mahmoud, Laila; Shahbeck, Noora; Lakhani, Shenela; AlMulla, Mariam; Nawaz, Zafar; Vitazka, Patrik; Alkuraya, Fowzan S; Ben-Omran, Tawfeg

2015-09-01

Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qatar with suspected Mendelian, mainly neurocognitive phenotypes, underwent CES from July 2012 to June 2014. Intellectual disability and global developmental delay were the most common clinical presentations but our cohort displayed other phenotypes, such as epilepsy, dysmorphism, microcephaly and other structural brain anomalies and autism. A pathogenic or likely pathogenic mutation, including pathogenic CNVs, was identified in 89 probands for a diagnostic yield of 60%. Consanguinity and positive family history predicted a higher diagnostic yield. In 5% (7/149) of cases, CES implicated novel candidate disease genes (MANF, GJA9, GLG1, COL15A1, SLC35F5, MAGE4, NEUROG1). CES uncovered two coexisting genetic disorders in 4% (6/149) and actionable incidental findings in 2% (3/149) of cases. Average time to diagnosis was reduced from 27 to 5 months. CES, which already has the highest diagnostic yield among all available diagnostic tools in the setting of Mendelian disorders, appears to be particularly helpful diagnostically in the highly consanguineous Middle Eastern population.

Adherence to Standards for Reporting Diagnostic Accuracy in Emergency Medicine Research.

PubMed

Gallo, Lucas; Hua, Nadia; Mercuri, Mathew; Silveira, Angela; Worster, Andrew

2017-08-01

Diagnostic tests are used frequently in the emergency department (ED) to guide clinical decision making and, hence, influence clinical outcomes. The Standards for Reporting of Diagnostic Accuracy (STARD) criteria were developed to ensure that diagnostic test studies are performed and reported to best inform clinical decision making in the ED. The objective was to determine the extent to which diagnostic studies published in emergency medicine journals adhered to STARD 2003 criteria. Diagnostic studies published in eight MEDLINE-listed, peer-reviewed, emergency medicine journals over a 5-year period were reviewed for compliance to STARD criteria. A total of 12,649 articles were screened and 114 studies were included in our study. Twenty percent of these were randomly selected for assessment using STARD 2003 criteria. Adherence to STARD 2003 reporting standards for each criteria ranged from 8.7% adherence (criteria-reporting adverse events from performing index test or reference standard) to 100% (multiple criteria). Just over half of STARD criteria are reported in more than 80% studies. As poorly reported studies may negatively impact their clinical usefulness, it is essential that studies of diagnostic test accuracy be performed and reported adequately. Future studies should assess whether studies have improved compliance with the STARD 2015 criteria amendment. © 2017 by the Society for Academic Emergency Medicine.

Problem-solving strategies in psychiatry: differences between experts and novices in diagnostic accuracy and reasoning.

PubMed

Gabriel, Adel; Violato, Claudio

2013-01-01

The purpose of this study was to examine and compare diagnostic success and its relationship with the diagnostic reasoning process between novices and experts in psychiatry. Nine volunteers, comprising five expert psychiatrists and four clinical clerks, completed a think-aloud protocol while attempting to make a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of a selected case with both Axis I and Axis III diagnoses. Expert psychiatrists made significantly more successful diagnoses for both the primary psychiatric and medical diagnoses than clinical clerks. Expert psychiatrists also gave fewer differential options. Analyzing the think-aloud protocols, expert psychiatrists were much more organized, made fewer mistakes, and utilized significantly less time to access their knowledge than clinical clerks. Both novices and experts seemed to use the hypothetic-deductive and scheme-inductive approaches to diagnosis. However, experts utilized hypothetic-deductive approaches significantly more often than novices. The hypothetic-deductive diagnostic strategy was utilized more than the scheme-inductive approach by both expert psychiatrists and clinical clerks. However, a specific relationship between diagnostic reasoning and diagnostic success could not be identified in this small pilot study. The author recommends a larger study that would include a detailed analysis of the think-aloud protocols.

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

PubMed

Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

2015-01-01

To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

[The characteristics of medical technologies in emergency medical care hospital].

PubMed

Murakhovskiĭ, A G; Babenko, A I; Bravve, Iu I; Tataurova, E A

2013-01-01

The article analyzes the implementation of major 12 diagnostic and 17 treatment technologies applied during medical care of patients with 12 key nosology forms of diseases in departments of the emergency medical care hospital No 2 of Omsk. It is established that key groups of technologies in the implementation of diagnostic process are the laboratory clinical diagnostic analyses and common diagnostic activities at reception into hospital and corresponding departments. The percentage of this kind of activities is about 78.3% of all diagnostic technologies. During the realization of treatment process the priority technologies are common curative and rehabilitation activities, intensive therapy activities and clinical diagnostic monitoring activities. All of them consist 80.1% of all curative technologies.

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.

Development and evaluation of a culture-free microbiota profiling platform (MYcrobiota) for clinical diagnostics.

PubMed

Boers, Stefan A; Hiltemann, Saskia D; Stubbs, Andrew P; Jansen, Ruud; Hays, John P

2018-06-01

Microbiota profiling has the potential to greatly impact on routine clinical diagnostics by detecting DNA derived from live, fastidious, and dead bacterial cells present within clinical samples. Such results could potentially be used to benefit patients by influencing antibiotic prescribing practices or to generate new classical-based diagnostic methods, e.g., culture or PCR. However, technical flaws in 16S rRNA gene next-generation sequencing (NGS) protocols, together with the requirement for access to bioinformatics, currently hinder the introduction of microbiota analysis into clinical diagnostics. Here, we report on the development and evaluation of an "end-to-end" microbiota profiling platform (MYcrobiota), which combines our previously validated micelle PCR/NGS (micPCR/NGS) methodology with an easy-to-use, dedicated bioinformatics pipeline. The newly designed bioinformatics pipeline processes micPCR/NGS data automatically and summarizes the results in interactive, but simple web reports. In order to explore the utility of MYcrobiota in clinical diagnostics, 47 clinical samples (40 "damaged skin" samples and 7 synovial fluids) were investigated using routine bacterial culture as comparator. MYcrobiota confirmed the presence of bacterial DNA in 37/37 culture-positive samples and detected bacterial taxa in 2/10 culture-negative samples. Moreover, 36/38 potentially relevant aerobic bacterial taxa and 3/3 mixtures of anaerobic bacteria were identified using culture and MYcrobiota, with the sensitivity and specificity being 95%. Interestingly, the majority of the 448 bacterial taxa identified using MYcrobiota were not identified using culture, which could potentially have an impact on clinical decision-making. Taken together, the development of MYcrobiota is a promising step towards the introduction of microbiota analysis into clinical diagnostic laboratories.

[Virtual clinical diagnosis support system of degenerative stenosis of the lumbar spinal canal].

PubMed

Shevelev, I N; Konovalov, N A; Cherkashov, A M; Molodchenkov, A A; Sharamko, T G; Asiutin, D S; Nazarenko, A G

2013-01-01

The aim of the study was to develop a virtual clinical diagnostic support system of degenerative lumbar spinal stenosis on database of spine registry. Choice of criteria's for diagnostic system was made on symptom analysis of 298 patients with lumbar spinal stenosis. Also was analysed a group of patient with disc herniation's for sensitivity and specify assessment of developed diagnostic support system. Represented clinical diagnostic support system allows identifying patients with degenerative lumbar spinal stenosis on stage of patient's primary visit. System sensitivity and specify are 90 and 71% respectively. "Online" mode of diagnostic system in structure of spine registry provides maximal availability for specialists, regardless of their locations. Development of tools "medicine 2.0" is the actual direction for carrying out further researches with which carrying out the centralized baea collection by means of specialized registers helps.

A systematic analysis of commonly used antibodies in cancer diagnostics.

PubMed

Gremel, Gabriela; Bergman, Julia; Djureinovic, Dijana; Edqvist, Per-Henrik; Maindad, Vikas; Bharambe, Bhavana M; Khan, Wasif Ali Z A; Navani, Sanjay; Elebro, Jacob; Jirström, Karin; Hellberg, Dan; Uhlén, Mathias; Micke, Patrick; Pontén, Fredrik

2014-01-01

Immunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. A tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer. © 2013 John Wiley & Sons Ltd.

The Role of the Autism Diagnostic Observation Schedule in the Assessment of Autism Spectrum Disorders in School and Community Settings.

PubMed

Akshoomoff, Natacha; Corsello, Christina; Schmidt, Heather

2006-01-01

Autism diagnostic practices among school and clinical psychologists, particularly those using the Autism Diagnostic Observation Schedule (ADOS), were examined using national survey results (N = 132). School and clinical psychologists were similar in following the Best Practice Guidelines for screening, diagnosis and assessment, School psychologists were more likely to include a school or home observation and teacher report than clinical psychologists but evaluated significantly fewer children with autism spectrum disorders per year compared to clinical psychologists. School psychologists who were ADOS users were more likely to consider themselves autism experts and include a review of records than ADOS non-users. Perceived advantages of the ADOS included its strength in capturing ASD-specific behaviors and the standardized structure provided for observation, while diagnostic discrimination and required resources were the most commonly identified disadvantages.

[The inpatient treatment of patients with anorexia nervosa in German clinics].

PubMed

Föcker, Manuel; Heidemann-Eggert, Elke; Antony, Gisela; Becker, Katja; Egberts, Karin; Ehrlich, Stefan; Fleischhaker, Christian; Hahn, Freia; Jaite, Charlotte; Kaess, Michael; M E Schulze, Ulrike; Sinzig, Judith; Wagner, Catharina; Legenbauer, Tanja; Renner, Tobias; Wessing, Ida; Herpertz-Dahlmann, Beate; Hebebrand, Johannes; Bühren, Katharina

2017-09-01

The medium- and long-term effects and side effects of inpatient treatment of patients with anorexia nervosa is still a matter of debate. The German S3-guidelines underline the importance of providing specialized and competent treatment. In this article we focus on the inpatient service structure in German child and adolescent psychiatric clinics with regard to their diagnostic and therapeutic concepts. A self-devised questionnaire was sent to 163 German child and adolescent psychiatric clinics. The questionnaire focused on the characteristics of the respective clinic as well as its diagnostic and therapeutic strategies. All clinics with an inpatient service for patients with anorexia nervosa (N = 84) provide single-therapy, family-based interventions and psychoeducation. A target weight is defined in nearly all clinics, and the mean intended weight gain per week is 486 g (range: 200 g to 700 g/week; SD = 117). Certain diagnostic tests and therapeutic interventions are used heterogeneously. This is the first study investigating the inpatient service structure for patients with anorexia nervosa in German clinics. Despite the provision of guideline-based therapy in all clinics, heterogeneous approaches were apparent with respect to specific diagnostic and therapeutic concepts.

Measuring the impact of diagnostic decision support on the quality of clinical decision making: development of a reliable and valid composite score.

PubMed

Ramnarayan, Padmanabhan; Kapoor, Ritika R; Coren, Michael; Nanduri, Vasantha; Tomlinson, Amanda L; Taylor, Paul M; Wyatt, Jeremy C; Britto, Joseph F

2003-01-01

Few previous studies evaluating the benefits of diagnostic decision support systems have simultaneously measured changes in diagnostic quality and clinical management prompted by use of the system. This report describes a reliable and valid scoring technique to measure the quality of clinical decision plans in an acute medical setting, where diagnostic decision support tools might prove most useful. Sets of differential diagnoses and clinical management plans generated by 71 clinicians for six simulated cases, before and after decision support from a Web-based pediatric differential diagnostic tool (ISABEL), were used. A composite quality score was calculated separately for each diagnostic and management plan by considering the appropriateness value of each component diagnostic or management suggestion, a weighted sum of individual suggestion ratings, relevance of the entire plan, and its comprehensiveness. The reliability and validity (face, concurrent, construct, and content) of these two final scores were examined. Two hundred fifty-two diagnostic and 350 management suggestions were included in the interrater reliability analysis. There was good agreement between raters (intraclass correlation coefficient, 0.79 for diagnoses, and 0.72 for management). No counterintuitive scores were demonstrated on visual inspection of the sets. Content validity was verified by a consultation process with pediatricians. Both scores discriminated adequately between the plans of consultants and medical students and correlated well with clinicians' subjective opinions of overall plan quality (Spearman rho 0.65, p < 0.01). The diagnostic and management scores for each episode showed moderate correlation (r = 0.51). The scores described can be used as key outcome measures in a larger study to fully assess the value of diagnostic decision aids, such as the ISABEL system.

Accuracy of clinical tests in the diagnosis of anterior cruciate ligament injury: a systematic review.

PubMed

Swain, Michael S; Henschke, Nicholas; Kamper, Steven J; Downie, Aron S; Koes, Bart W; Maher, Chris G

2014-01-01

Numerous clinical tests are used in the diagnosis of anterior cruciate ligament (ACL) injury but their accuracy is unclear. The purpose of this study is to evaluate the diagnostic accuracy of clinical tests for the diagnosis of ACL injury. Systematic review. The review protocol was registered through PROSPERO (CRD42012002069). Electronic databases (PubMed, MEDLINE, EMBASE, CINAHL) were searched up to 19th of June 2013 to identify diagnostic studies comparing the accuracy of clinical tests for ACL injury to an acceptable reference standard (arthroscopy, arthrotomy, or MRI). Risk of bias was appraised using the QUADAS-2 checklist. Index test accuracy was evaluated using a descriptive analysis of paired likelihood ratios and displayed as forest plots. A total of 285 full-text articles were assessed for eligibility, from which 14 studies were included in this review. Included studies were deemed to be clinically and statistically heterogeneous, so a meta-analysis was not performed. Nine clinical tests from the history (popping sound at time of injury, giving way, effusion, pain, ability to continue activity) and four from physical examination (anterior draw test, Lachman's test, prone Lachman's test and pivot shift test) were investigated for diagnostic accuracy. Inspection of positive and negative likelihood ratios indicated that none of the individual tests provide useful diagnostic information in a clinical setting. Most studies were at risk of bias and reported imprecise estimates of diagnostic accuracy. Despite being widely used and accepted in clinical practice, the results of individual history items or physical tests do not meaningfully change the probability of ACL injury. In contrast combinations of tests have higher diagnostic accuracy; however the most accurate combination of clinical tests remains an area for future research. Clinicians should be aware of the limitations associated with the use of clinical tests for diagnosis of ACL injury.

FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease.

PubMed

Foster, Norman L; Heidebrink, Judith L; Clark, Christopher M; Jagust, William J; Arnold, Steven E; Barbas, Nancy R; DeCarli, Charles S; Turner, R Scott; Koeppe, Robert A; Higdon, Roger; Minoshima, Satoshi

2007-10-01

Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.

Phenomenology of Schizophrenia and the Representativeness of Modern Diagnostic Criteria.

PubMed

Kendler, Kenneth S

2016-10-01

This article aims to determine the degree to which modern operationalized diagnostic criteria for schizophrenia reflect the main clinical features of the disorder as described historically by diagnostic experts. Amazon.com, the National Library of Medicine, and Forgottenbooks.com were searched for articles written or translated into English from 1900 to 1960. Clinical descriptions of schizophrenia or dementia praecox appearing in 16 textbooks or review articles published between 1899 and 1956 were reviewed and compared with the criteria for schizophrenia from 6 modern US operationalized diagnostic systems. Twenty prominent symptoms and signs were reported by 5 or more authors. A strong association was seen between the frequency with which the symptoms/signs were reported and the likelihood of their presence in modern diagnostic systems. Of these 20 symptoms/signs, 3 (thought disorder, delusions, and hallucinations) were included in all diagnostic systems and were among the 4 most frequently reported. Three symptoms/signs were added then kept in subsequent criteria: emotional blunting, changes in volition, and changes in social life. Three symptoms/signs were added but then dropped: bizarre delusions, passivity symptoms, and mood incongruity. Eleven symptoms/signs were never included in any diagnostic system. Compared with historical authors, modern criteria favored symptoms over signs. Odd movements and postures, noted by 16 of 18 historical authors, were absent from all modern criteria. DSM-5 criteria contain 6 of the 20 historically noted symptoms/signs. Although modern operationalized criteria for schizophrenia reflect symptoms and signs commonly reported by historical experts, many clinical features emphasized by these experts are absent from modern criteria. This is not necessarily problematic as diagnostic criteria are meant to index rather than thoroughly describe syndromes. However, the lack of correspondence in schizophrenia between historically important symptoms/signs and current diagnostic systems highlights the limitations of clinical evaluations and research studies that restrict the diagnostic assessments to current diagnostic criteria. We should not confuse our DSM diagnostic criteria with the disorders that they were designed to index.

Evaluating online diagnostic decision support tools for the clinical setting.

PubMed

Pryor, Marie; White, David; Potter, Bronwyn; Traill, Roger

2012-01-01

Clinical decision support tools available at the point of care are an effective adjunct to support clinicians to make clinical decisions and improve patient outcomes. We developed a methodology and applied it to evaluate commercially available online clinical diagnostic decision support (DDS) tools for use at the point of care. We identified 11 commercially available DDS tools and assessed these against an evaluation instrument that included 6 categories; general information, content, quality control, search, clinical results and other features. We developed diagnostically challenging clinical case scenarios based on real patient experience that were commonly missed by junior medical staff. The evaluation was divided into 2 phases; an initial evaluation of all identified and accessible DDS tools conducted by the Clinical Information Access Portal (CIAP) team and a second phase that further assessed the top 3 tools identified in the initial evaluation phase. An evaluation panel consisting of senior and junior medical clinicians from NSW Health conducted the second phase. Of the eleven tools that were assessed against the evaluation instrument only 4 tools completely met the DDS definition that was adopted for this evaluation and were able to produce a differential diagnosis. From the initial phase of the evaluation 4 DDS tools scored 70% or more (maximum score 96%) for the content category, 8 tools scored 65% or more (maximum 100%) for the quality control category, 5 tools scored 65% or more (maximum 94%) for the search category, and 4 tools score 70% or more (maximum 81%) for the clinical results category. The second phase of the evaluation was focused on assessing diagnostic accuracy for the top 3 tools identified in the initial phase. Best Practice ranked highest overall against the 6 clinical case scenarios used. Overall the differentiating factor between the top 3 DDS tools was determined by diagnostic accuracy ranking, ease of use and the confidence and credibility of the clinical information. The evaluation methodology used here to assess the quality and comprehensiveness of clinical DDS tools was effective in identifying the most appropriate tool for the clinical setting. The use of clinical case scenarios is fundamental in determining the diagnostic accuracy and usability of the tools.

Quality of referral: What information should be included in a request for diagnostic imaging when a patient is referred to a clinical radiologist?

PubMed

G Pitman, Alexander

2017-06-01

Referral to a clinical radiologist is the prime means of communication between the referrer and the radiologist. Current Australian and New Zealand government regulations do not prescribe what clinical information should be included in a referral. This work presents a qualitative compilation of clinical radiologist opinion, relevant professional recommendations, governmental regulatory positions and prior work on diagnostic error to synthesise recommendations on what clinical information should be included in a referral. Recommended requirements on what clinical information should be included in a referral to a clinical radiologist are as follows: an unambiguous referral; identity of the patient; identity of the referrer; and sufficient clinical detail to justify performance of the diagnostic imaging examination and to confirm appropriate choice of the examination and modality. Recommended guideline on the content of clinical detail clarifies when the information provided in a referral meets these requirements. High-quality information provided in a referral allows the clinical radiologist to ensure that exposure of patients to medical radiation is justified. It also minimises the incidence of perceptual and interpretational diagnostic error. Recommended requirements and guideline on the clinical detail to be provided in a referral to a clinical radiologist have been formulated for professional debate and adoption. © 2017 The Royal Australian and New Zealand College of Radiologists.

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.

What's in a Label? Is Diagnosis the Start or the End of Clinical Reasoning?

PubMed

Ilgen, Jonathan S; Eva, Kevin W; Regehr, Glenn

2016-04-01

Diagnostic reasoning has received substantial attention in the literature, yet what we mean by "diagnosis" may vary. Diagnosis can align with assignment of a "label," where a constellation of signs, symptoms, and test results is unified into a solution at a single point in time. This "diagnostic labeling" conceptualization is embodied in our case-based learning curricula, published case reports, and research studies, all of which treat diagnostic accuracy as the primary outcome. However, this conceptualization may oversimplify the richly iterative and evolutionary nature of clinical reasoning in many settings. Diagnosis can also represent a process of guiding one's thoughts by "making meaning" from data that are intrinsically dynamic, experienced idiosyncratically, negotiated among team members, and rich with opportunities for exploration. Thus, there are two complementary constructions of diagnosis: 1) the correct solution resulting from a diagnostic reasoning process, and 2) a dynamic aid to an ongoing clinical reasoning process. This article discusses the importance of recognizing these two conceptualizations of "diagnosis," outlines the unintended consequences of emphasizing diagnostic labeling as the primary goal of clinical reasoning, and suggests how framing diagnosis as an ongoing process of meaning-making might change how we think about teaching and assessing clinical reasoning.

Integration of basic sciences and clinical sciences in oral radiology education for dental students.

PubMed

Baghdady, Mariam T; Carnahan, Heather; Lam, Ernest W N; Woods, Nicole N

2013-06-01

Educational research suggests that cognitive processing in diagnostic radiology requires a solid foundation in the basic sciences and knowledge of the radiological changes associated with disease. Although it is generally assumed that dental students must acquire both sets of knowledge, little is known about the most effective way to teach them. Currently, the basic and clinical sciences are taught separately. This study was conducted to compare the diagnostic accuracy of students when taught basic sciences segregated or integrated with clinical features. Predoctoral dental students (n=51) were taught four confusable intrabony abnormalities using basic science descriptions integrated with the radiographic features or taught segregated from the radiographic features. The students were tested with diagnostic images, and memory tests were performed immediately after learning and one week later. On immediate and delayed testing, participants in the integrated basic science group outperformed those from the segregated group. A main effect of learning condition was found to be significant (p<0.05). The results of this study support the critical role of integrating biomedical knowledge in diagnostic radiology and shows that teaching basic sciences integrated with clinical features produces higher diagnostic accuracy in novices than teaching basic sciences segregated from clinical features.

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

Diagnosis of Polycystic Ovary Syndrome: AMH in combination with clinical symptoms.

PubMed

Sahmay, Sezai; Aydin, Yavuz; Oncul, Mahmut; Senturk, Levent M

2014-02-01

We assessed the utility of using anti-Müllerian hormone (AMH) and clinical features of polycystic ovary syndrome (PCOS), polycystic ovarian morphology (PCOM), oligo/amenorrhea (OA), and hyperandrogenism (HA) for diagnosing PCOS, and compared their diagnostic accuracy with those of classical diagnostic systems. A total of 606 females were admitted to a university hospital with menstrual irregularities or symptoms of hyperandrogenism were enrolled in this cross-sectional study. Fasting blood samples were collected. Pelvic and/or abdominal ultrasonography and clinical examination were performed. Patients were evaluated for the presence of PCOS according to conventional diagnostic criteria. The diagnostic performance of using serum AMH levels alone and in various combinations with the clinical features of PCOM, OA, and HA were investigated. For the diagnosis of PCOS, the combination of OA and/or HA with AMH showed 83% sensitivity and 100% specificity according to the Rotterdam criteria; 83% sensitivity and 89% specificity according to the National Institutes of Health (NIH) criteria; and 82% sensitivity and 93.5% specificity according to the Androgen Excess Society (AES) criteria. The serum AMH level is a useful diagnostic marker for PCOS and is correlated with conventional diagnostic criteria. The combination of AMH level with OA and/or HA markedly increased the clinical scope for PCOS diagnosis and can be introduced as a possible objective criterion for the diagnosis of this disease.

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group

PubMed Central

Tsalik, Ephraim L.; Petzold, Elizabeth; Kreiswirth, Barry N.; Bonomo, Robert A.; Banerjee, Ritu; Lautenbach, Ebbing; Evans, Scott R.; Hanson, Kimberly E.; Klausner, Jeffrey D.

2017-01-01

Abstract Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. PMID:28350903

Flexible substrate-based devices for point-of-care diagnostics

PubMed Central

Wang, ShuQi; Chinnasamy, Thiruppathiraja; Lifson, Mark; Inci, Fatih; Demirci, Utkan

2016-01-01

Point-of-care (POC) diagnostics play an important role in delivering healthcare, particularly for clinical management and disease surveillance in both developed and developing countries. Currently, the majority of POC diagnostics utilize paper substrates owing to their affordability, disposability, and mass production capability. Recently, flexible polymer substrates have been investigated due to their enhanced physicochemical properties, potential to be integrated into wearable devices with wireless communications for personalized health monitoring, and ability to be customized for POC diagnostics. Here, we focus on the latest advances in developing flexible substrate-based diagnostic devices, including paper and polymers, and their clinical applications at the POC. PMID:27344425

Flexible Substrate-Based Devices for Point-of-Care Diagnostics.

PubMed

Wang, ShuQi; Chinnasamy, Thiruppathiraja; Lifson, Mark A; Inci, Fatih; Demirci, Utkan

2016-11-01

Point-of-care (POC) diagnostics play an important role in delivering healthcare, particularly for clinical management and disease surveillance in both developed and developing countries. Currently, the majority of POC diagnostics utilize paper substrates owing to affordability, disposability, and mass production capability. Recently, flexible polymer substrates have been investigated due to their enhanced physicochemical properties, potential to be integrated into wearable devices with wireless communications for personalized health monitoring, and ability to be customized for POC diagnostics. Here, we focus on the latest advances in developing flexible substrate-based diagnostic devices, including paper and polymers, and their clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinically expedient reporting of rapid diagnostic test information.

PubMed

Doern, G V

1986-03-01

With the development of rapid diagnostic tests in the clinical microbiology laboratory has come an awareness of the importance of rapid results reporting. Clearly, the potential clinical impact of rapid diagnostic tests is dependent on expeditious reporting. Traditional manual reporting systems are encumbered by the necessity of transcription of test information onto hard copy reports and then the subsequent distribution of such reports into the hands of the user. Laboratory computers when linked directly to CRTs located in nursing stations, ambulatory clinics, or physician's offices, both inside and outside of the hospital, permit essentially instantaneous transfer of test results from the laboratory to the clinician. Computer-assisted results reporting, while representing a significant advance over manual reporting systems is not, however, without problems. Concerns include validation of test information, authorization of users with access to test information, mechanical integrity, and cost. These issues notwithstanding, computerized results reporting will undoubtedly play a central role in optimizing the clinical impact of rapid diagnostic tests.

Prevalence of neuropathic features of back pain in clinical populations: implications for the diagnostic triage paradigm.

PubMed

Hush, Julia M; Marcuzzi, Anna

2012-07-01

SUMMARY Contemporary clinical assessment of back pain is based on the diagnostic triage paradigm. The most common diagnostic classification is nonspecific back pain, considered to be of nociceptive etiology. A small proportion are diagnosed with radicular pain, of neuropathic origin. In this study we review the body of literature on the prevalence of neuropathic features of back pain, revealing that the point prevalence is 17% in primary care, 34% in mixed clinical settings and 53% in tertiary care. There is evidence that neuropathic features of back pain are not restricted to typical clinical radicular pain phenotypes and may be under-recognized, particularly in primary care. The consequence of this is that in the clinic, diagnostic triage may erroneously classify patients with nonspecific back pain or radicular pain. A promising alternative is the development of mechanism-based pain phenotyping in patients with back pain. Timely identification of contributory pain mechanisms may enable greater opportunity to select appropriate therapeutic targets and improve patient outcomes.

Ethical aspects of personality disorders.

PubMed

Bendelow, Gillian

2010-11-01

To review recent literature around the controversial diagnosis of personality disorder, and to assess the ethical aspects of its status as a medical disorder. The diagnostic currency of personality disorder as a psychiatric/medical disorder has a longstanding history of ethical and social challenges through critiques of the medicalization of deviance. More recently controversies by reflexive physicians around the inclusion of the category in the forthcoming revisions of International Classification of Diseases and Diagnostic and Statistical Manual of Mental Disorders classifications reflect the problems of value-laden criteria, with the diagnostic category being severely challenged from within psychiatry as well as from without. The clinical diagnostic criteria for extremely value-laden psychiatric conditions such as personality disorder need to be analyzed through the lens of values-based medicine, as well as through clinical evidence, as the propensity for political and sociolegal appropriation of the categories can render their clinical and diagnostic value meaningless.

Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

PubMed

Muzyka, Iryna M; Estephan, Bachir

2018-01-01

The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

Single-cell proteomics: potential implications for cancer diagnostics.

PubMed

Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

2016-01-01

Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

An evidence-based diagnostic classification system for low back pain

PubMed Central

Vining, Robert; Potocki, Eric; Seidman, Michael; Morgenthal, A. Paige

2013-01-01

Introduction: While clinicians generally accept that musculoskeletal low back pain (LBP) can arise from specific tissues, it remains difficult to confirm specific sources. Methods: Based on evidence supported by diagnostic utility studies, doctors of chiropractic functioning as members of a research clinic created a diagnostic classification system, corresponding exam and checklist based on strength of evidence, and in-office efficiency. Results: The diagnostic classification system contains one screening category, two pain categories: Nociceptive, Neuropathic, one functional evaluation category, and one category for unknown or poorly defined diagnoses. Nociceptive and neuropathic pain categories are each divided into 4 subcategories. Conclusion: This article describes and discusses the strength of evidence surrounding diagnostic categories for an in-office, clinical exam and checklist tool for LBP diagnosis. The use of a standardized tool for diagnosing low back pain in clinical and research settings is encouraged. PMID:23997245

[EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

PubMed

Zhdanov, K V; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fisun, A Ya

2015-01-01

The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

The Health Technology Assessment of companion diagnostics: experience of NICE.

PubMed

Byron, Sarah K; Crabb, Nick; George, Elisabeth; Marlow, Mirella; Newland, Adrian

2014-03-15

Companion diagnostics are used to aid clinical decision making to identify patients who are most likely to respond to treatment. They are becoming increasingly important as more new pharmaceuticals receive licensed indications that require the use of a companion diagnostic to identify the appropriate patient subgroup for treatment. These pharmaceuticals have proven benefit in the treatment of some cancers and other diseases, and also have potential to precisely tailor treatments to the individual in the future. However, the increasing use of companion diagnostics could place a substantial burden on health system resources to provide potentially high volumes of testing. This situation, in part, has led policy makers and Health Technology Assessment (HTA) bodies to review the policies and methods used to make reimbursement decisions for pharmaceuticals requiring companion diagnostics. The assessment of a pharmaceutical alongside the companion diagnostic used in the clinical trials may be relatively straightforward, although there are a number of challenges associated with assessing pharmaceuticals where a range of alternative companion diagnostics are available for use in routine clinical practice. The UK HTA body, the National Institute for Health and Care Excellence (NICE), has developed policy for considering companion diagnostics using its Technology Appraisal and Diagnostics Assessment Programs. Some HTA bodies in other countries have also adapted their policies and methods to accommodate the assessment of companion diagnostics. Here, we provide insight into the HTA of companion diagnostics for reimbursement decisions and how the associated challenges are being addressed, in particular by NICE. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study.

PubMed

Moon, Chang Mo; Jung, Sung-Ae; Kim, Seong-Eun; Song, Hyun Joo; Jung, Yunho; Ye, Byong Duk; Cheon, Jae Hee; Kim, You Sun; Kim, Young-Ho; Kim, Joo Sung; Han, Dong Soo

2015-01-01

Diagnostic delay frequently occurs in Crohn's disease (CD) patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn's Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years) (p = 0.014), concomitant upper gastrointestinal (UGI) disease (p = 0.012) and penetrating disease behavior at diagnosis (p = 0.001) were positively associated with long diagnostic delay (≥18 months). During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07-1.93; p = 0.017), internal fistulas (HR, 1.62; 95% CI, 1.12-2.33; p = 0.011), and perianal fistulas (HR, 1.38; 95% CI, 1.06-1.80; p = 0.016). However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas.

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD-'Assessing QbTest Utility in ADHD' (AQUA): a randomised controlled trial.

PubMed

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-12-01

The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current 'gold standard' ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. This multisite randomised controlled trial will recruit young people (aged 6-17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval. NCT02209116. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD—‘Assessing QbTest Utility in ADHD’ (AQUA): a randomised controlled trial

PubMed Central

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-01-01

Introduction The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current ‘gold standard’ ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. Methods and analysis This multisite randomised controlled trial will recruit young people (aged 6–17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. Ethics and dissemination The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval. Trial registration number NCT02209116. PMID:25448628

[Principles of cooperation between the specialties of internal medicine, pathology and clinical biochemistry].

PubMed

Hölzel, W; Baumgarten, R; Fiedler, H; Zimmermann, S

1985-12-01

The optimal utilization of the knowledge and possibilities of pathological and clinical biochemistry presumes a close cooperation between it and the clinical specialties. The common working team of the GDR Society of Internal Medicine and the GDR Society for Clinical Chemistry and Laboratory Diagnostics makes theses of the central points of the cooperation in care, education, further education and postgraduate study and in research a subject for discussion. As essential tasks in the process of medical care are regarded the balance of the examination programme standing at the disposal, the establishment of diagnostic programmes, the establishment of organisational measures, the ascertainment of a use according to indication, the guarantee of the representance of examination material, the control of plausibility and the interpretation of test results. Since the realization of the tasks to a large extent depends on the cooperation of the specialities in education, further education and postgraduate study during the further education the clinician should become acquainted with the possibilities, the limits and the prerequisites for the performance of laboratory diagnostic investigations, the clinical biochemist with the problems of medical care and the value of the laboratory diagnosis in the total process of the treatment. In the field of research the result is a necessary cooperation in the clarification of patho-biochemical mechanisms, in the search for suitable laboratory diagnostic parameters for diagnostics and control of the course as well as in the statement of the validity of laboratory diagnostic parameters and parameter combinations taking into consideration the factors expenses, benefit and risk as well as further diagnostic possibilities.

ROC curves in clinical chemistry: uses, misuses, and possible solutions.

PubMed

Obuchowski, Nancy A; Lieber, Michael L; Wians, Frank H

2004-07-01

ROC curves have become the standard for describing and comparing the accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by clinical chemists. Our aims were to observe how the accuracy of clinical laboratory diagnostic tests is assessed, compared, and reported in the literature; to identify common problems with the use of ROC curves; and to offer some possible solutions. We reviewed every original work using ROC curves and published in Clinical Chemistry in 2001 or 2002. For each article we recorded phase of the research, prospective or retrospective design, sample size, presence/absence of confidence intervals (CIs), nature of the statistical analysis, and major analysis problems. Of 58 articles, 31% were phase I (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced) studies. The studies increased in sample size from phase I to III and showed a progression in the use of prospective designs. Most phase I studies were powered to assess diagnostic tests with ROC areas >/=0.70. Thirty-eight percent of studies failed to include CIs for diagnostic test accuracy or the CIs were constructed inappropriately. Thirty-three percent of studies provided insufficient analysis for comparing diagnostic tests. Other problems included dichotomization of the gold standard scale and inappropriate analysis of the equivalence of two diagnostic tests. We identify available software and make some suggestions for sample size determination, testing for equivalence in diagnostic accuracy, and alternatives to a dichotomous classification of a continuous-scale gold standard. More methodologic research is needed in areas specific to clinical chemistry.

Hazardous Waste Cleanup: Ortho-Clinical Diagnostics, Raritan, New Jersey

EPA Pesticide Factsheets

Ortho-Clinical Diagnostics (OCD) is an administration and manufacturing facility located at 1001 U.S. Route 202 North in Raritan Borough, Somerset County, New Jersey. The facility manufactures hospital and laboratory reagents used primarily for blood

Cognitive aspect of diagnostic errors.

PubMed

Phua, Dong Haur; Tan, Nigel C K

2013-01-01

Diagnostic errors can result in tangible harm to patients. Despite our advances in medicine, the mental processes required to make a diagnosis exhibits shortcomings, causing diagnostic errors. Cognitive factors are found to be an important cause of diagnostic errors. With new understanding from psychology and social sciences, clinical medicine is now beginning to appreciate that our clinical reasoning can take the form of analytical reasoning or heuristics. Different factors like cognitive biases and affective influences can also impel unwary clinicians to make diagnostic errors. Various strategies have been proposed to reduce the effect of cognitive biases and affective influences when clinicians make diagnoses; however evidence for the efficacy of these methods is still sparse. This paper aims to introduce the reader to the cognitive aspect of diagnostic errors, in the hope that clinicians can use this knowledge to improve diagnostic accuracy and patient outcomes.

Clinical pathologist in Korea--training program and its roles in laboratories.

PubMed

Cho, Han-Ik; Lee, Kap No; Park, Jong-Woo; Park, Hyosoon; Kwak, Yun Sik

2002-01-01

A rapid development of practice of laboratory medicine in Korea owes its success to the clinical pathologists (CP), who have played a role of a pathfinder for laboratories. The Korean CP postgraduate education (residency) program is unique in that it is exclusively for laboratory medicine. The training program for clinical pathologists includes diagnostic hematology, diagnostic immunology, clinical microbiology, clinical chemistry, blood bank, diagnostic genetics, informatics and laboratory management. The program has produced a strong group of about 600 laboratory physicians, officially clinical pathologists since 1963. Most of Korean clinical pathologists work as laboratory directors, directors of university hospital laboratories or teaching faculty members in medical schools. The roles of clinical pathologists are laboratory management, interpretation of laboratory test results, clinical consulting services to clinicians and patients, ordering secondary tests after reviews of requested test results and utilization management. The clinical pathologists have developed clinical laboratories to be a main contributor for improved medical practice. During the last 40 years under the turbulent healthcare system, clinical pathologists have significantly contributed to safeguard the laboratory interests. The education program and the role of clinical pathologists are described.

Examining Curricular Integration Strategies To Optimize Learning Of The Anatomical Sciences

NASA Astrophysics Data System (ADS)

Lisk, Kristina Adriana Ayako

Background: Integration of basic and clinical science knowledge is essential to clinical practice. Although the importance of these two knowledge domains is well-recognized, successfully supporting the development of learners' integrated basic and clinical science knowledge, remains an educational challenge. In this dissertation, I examine curricular integration strategies to optimize learning of the anatomical sciences. Objectives: The studies were designed to achieve the following research aims: 1) to objectively identify clinically relevant content for an integrated musculoskeletal anatomy curriculum; 2) to examine the value of integrated anatomy and clinical science instruction compared to clinical science instruction alone on novices' diagnostic accuracy and diagnostic reasoning process; 3) to compare the effect of integrating and segregating anatomy and clinical science instruction along with a learning strategy (self-explanation) on novices' diagnostic accuracy. Methods: A modified Delphi was used to objectively select clinically relevant content for an integrated musculoskeletal anatomy curriculum. Two experimental studies were created to compare different instructional strategies to optimize learning of the curricular content. In both of these studies, novice learners were taught the clinical features of musculoskeletal pathologies using different learning approaches. Diagnostic performance was measured immediately after instruction and one-week later. Results: The results show that the Delphi method is an effective strategy to select clinically relevant content for integrated anatomy curricula. The findings also demonstrate that novices who were explicitly taught the clinical features of musculoskeletal diseases using causal basic science descriptions had superior diagnostic accuracy and a better understanding of the relative importance of key clinical features for disease categories. Conclusions: This research demonstrates how integration strategies can be applied at multiple levels of the curriculum. Further, this work shows the value of cognitive integration of anatomy and clinical science and it emphasizes the importance of purposefully linking the anatomical and clinical sciences in day-to-day teaching.

The Use and Abuse of Diagnostic/Classification Criteria

PubMed Central

June, Rayford R.; Aggarwal, Rohit

2015-01-01

In rheumatic diseases, classification criteria have been developed to identify well-defined homogenous cohorts for clinical research. Although, they are commonly used in clinical practice, their use may not be appropriate for routine diagnostic clinical care. Classification criteria are being revised with improved methodology and further understanding of disease pathophysiology, but still may not encompass all unique clinical situations to be applied for diagnosis of heterogeneous, rare, evolving rheumatic diseases. Diagnostic criteria development is challenging primarily due to difficulty for universal application given significant differences in prevalence of rheumatic diseases based on geographical area and clinic settings. Despite these shortcomings, the clinician can still use classification criteria for understanding the disease as well as a guide for diagnosis with a few caveats. We present the limits of current classification criteria, describe their use and abuse in clinical practice, and how they should be used with caution when applied in clinics. PMID:26096094

Measures to Improve Diagnostic Safety in Clinical Practice.

PubMed

Singh, Hardeep; Graber, Mark L; Hofer, Timothy P

2016-10-20

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of "diagnostic safety" related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health-care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Identification of facilitators and barriers to residents' use of a clinical reasoning tool.

PubMed

DiNardo, Deborah; Tilstra, Sarah; McNeil, Melissa; Follansbee, William; Zimmer, Shanta; Farris, Coreen; Barnato, Amber E

2018-03-28

While there is some experimental evidence to support the use of cognitive forcing strategies to reduce diagnostic error in residents, the potential usability of such strategies in the clinical setting has not been explored. We sought to test the effect of a clinical reasoning tool on diagnostic accuracy and to obtain feedback on its usability and acceptability. We conducted a randomized behavioral experiment testing the effect of this tool on diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a single internal medical residency program in 2014. Residents completed written clinical cases in a proctored setting with and without prompts to use the tool. The tool encouraged reflection on concordant and discordant aspects of each case. We used random effects regression to assess the effect of the tool on diagnostic accuracy of the independent case sets, controlling for case complexity. We then conducted audiotaped structured focus group debriefing sessions and reviewed the tapes for facilitators and barriers to use of the tool. Of 51 eligible PGY-3 residents, 34 (67%) participated in the study. The average diagnostic accuracy increased from 52% to 60% with the tool, a difference that just met the test for statistical significance in adjusted analyses (p=0.05). Residents reported that the tool was generally acceptable and understandable but did not recognize its utility for use with simple cases, suggesting the presence of overconfidence bias. A clinical reasoning tool improved residents' diagnostic accuracy on written cases. Overconfidence bias is a potential barrier to its use in the clinical setting.

Contrast-enhanced postmortem computed tomography in clinical pathology: enhanced value of 20 clinical autopsies.

PubMed

Westphal, Saskia E; Apitzsch, Jonas C; Penzkofer, Tobias; Kuhl, Christiane K; Mahnken, Andreas H; Knüchel, Ruth

2014-09-01

Postmortem computed tomography (PMCT) is a modern tool that complements autopsy diagnostics. In clinical autopsies, a major cause of death is cardiovascular disease. To improve the performance of PMCT in cardiovascular disease, full body angiography was developed (PMCT angiography [PMCTA]). Twenty PMCTA scans generated before autopsy were compared with native PMCT and clinical autopsy. The objective of the study was to quantify the additional diagnostic value of adding angiography to native imaging and to compare PMCT and PMCTA findings to autopsy findings. The diagnosis of the cause of death was identical or overlapped in 80% of the cases that used PMCTA and 70% that used PMCT. The additional diagnostic yield given by PMCT and PMCTA in combination with autopsy was 55%. PMCT yielded additional diagnoses in the musculoskeletal system. The greatest additional diagnostic value of PMCTA was in association with cardiovascular diagnoses. The accuracy of PMCTA for cardiac causes of death was 80%, and the positive predictive value was 90%. The findings indicate that native PMCT cannot display the cardiovascular system sufficiently clearly for high-quality diagnostic assessment. However, PMCTA is a powerful tool in autopsy cases with a history of cardiovascular disease and/or a suspected cardiovascular cause of death. The combination of PMCTA and clinical autopsy enhances diagnostic quality and completeness of the autopsy report. Furthermore, in cases without consent or with a restricted consent for clinical autopsy, PMCTA has the potential to provide information on cardiovascular causes of death. Copyright © 2014 Elsevier Inc. All rights reserved.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks.

PubMed

Schneider, Daniel; Riegman, Peter H J; Cronin, Maureen; Negrouk, Anastassia; Moch, Holger; Balling, Rudi; Penault-Llorca, Frederiques; Zatloukal, Kurt; Horgan, Denis

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research. © 2016 S. Karger AG, Basel.

Methodologic Guide for Evaluating Clinical Performance and Effect of Artificial Intelligence Technology for Medical Diagnosis and Prediction.

PubMed

Park, Seong Ho; Han, Kyunghwa

2018-03-01

The use of artificial intelligence in medicine is currently an issue of great interest, especially with regard to the diagnostic or predictive analysis of medical images. Adoption of an artificial intelligence tool in clinical practice requires careful confirmation of its clinical utility. Herein, the authors explain key methodology points involved in a clinical evaluation of artificial intelligence technology for use in medicine, especially high-dimensional or overparameterized diagnostic or predictive models in which artificial deep neural networks are used, mainly from the standpoints of clinical epidemiology and biostatistics. First, statistical methods for assessing the discrimination and calibration performances of a diagnostic or predictive model are summarized. Next, the effects of disease manifestation spectrum and disease prevalence on the performance results are explained, followed by a discussion of the difference between evaluating the performance with use of internal and external datasets, the importance of using an adequate external dataset obtained from a well-defined clinical cohort to avoid overestimating the clinical performance as a result of overfitting in high-dimensional or overparameterized classification model and spectrum bias, and the essentials for achieving a more robust clinical evaluation. Finally, the authors review the role of clinical trials and observational outcome studies for ultimate clinical verification of diagnostic or predictive artificial intelligence tools through patient outcomes, beyond performance metrics, and how to design such studies. © RSNA, 2018.

Diagnostic accuracy of clinical tests for assessment of hamstring injury: a systematic review.

PubMed

Reiman, Michael P; Loudon, Janice K; Goode, Adam P

2013-04-01

Systematic literature review. The diagnosis of a hamstring injury has traditionally relied on various clinical measures (eg, palpation, swelling, manual resistance), as well as the use of diagnostic imaging. But a few studies have suggested the use of specific clinical tests that may be helpful for the diagnostic process. To summarize the current literature on the diagnostic accuracy of orthopaedic special tests for hamstring injuries and to determine their clinical utility. A computer-assisted literature search of the MEDLINE, CINAHL, and Embase databases (along with a manual search of grey literature) was conducted using key words related to diagnostic accuracy of hamstring injuries. To be considered for inclusion in the review, the study required (1) patients with hamstring or posterior thigh pain; (2) a cohort, case-control, or cross-sectional design; (3) inclusion of at least 1 clinical examination test used to evaluate hamstring pathology; (4) comparison against an acceptable reference standard; (5) reporting of diagnostic accuracy of the measures (sensitivity [SN], specificity [SP], or likelihood ratios); and (6) publication in English. SN, SP, and positive and negative likelihood ratios were calculated for each diagnostic test. The search strategy identified 602 potential articles, of which only 3 articles met the inclusion criteria, with only 1 of these 3 articles being of high quality. Two of the studies investigated a single special test, whereas the third article examined a composite clinical assessment employing various special tests. The SN values ranged from 0.55 (95% confidence interval [CI]: 0.46, 0.69) for the active range-of-motion test to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test. The SP values ranged from 0.03 (95% CI: 0.00, 0.22) for the composite clinical assessment to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test, active range-of-motion test, passive range-of-motion test, and resisted range-of-motion test. The use of a single special test demonstrated stronger SP than SN properties, whereas the composite clinical assessment demonstrated stronger SN than SP properties. Very few studies have investigated the utilization of clinical special tests for the diagnosis of hamstring injuries. Further studies of higher quality design are suggested prior to advocating independent clinical utilization of these special tests. Diagnosis, level 3b.

Diagnostic games: from adequate formalization of clinical experience to structure discovery.

PubMed

Shifrin, Michael A; Kasparova, Eva I

2008-01-01

A method of obtaining well-founded and reproducible results in clinical decision making is presented. It is based on "diagnostic games", a procedure of elicitation and formalization of experts' knowledge and experience. The use of this procedure allows formulating decision rules in the terms of an adequate language, that are both unambiguous and clinically clear.

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PubMed Central

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-01-01

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort. PMID:28771251

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PubMed

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-04-01

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Cheyletiella infestation in the dog: observations on diagnostic methods and clinical signs.

PubMed

Saevik, B K; Bredal, W; Ulstein, T L

2004-10-01

The aims of this study were to evaluate the ability of diagnostic methods to detect naturally occurring Cheyletiella infestation in dogs, and to quantify and relate the number of mites and eggs present to clinical signs. Privately owned dogs with skin problems were eligible for inclusion in the study. Four diagnostic tests were performed on each dog in the following order: tape impression, hair plucking, skin scraping and vacuum cleaning. Dogs with positive test results for Cheyletiella infestation in at least one of the tests under evaluation were included in the study (n=27). The severity of pruritus and scaling was graded on a four-point fixed scale. The diagnostic findings in vacuum cleaning samples provided a semiquantitative measure of the grade of infestation. The vacuum cleaning test gave a positive test result in all dogs and was significantly more efficient than the other tests evaluated (P<0.01). The number of diagnostic findings varied considerably among the different vacuum samples. No significant relationship between the number of diagnostic findings and severity of clinical signs was detected.

Are all after-hours diagnostic imaging appropriate? An Australian Emergency Department pilot study.

PubMed

Gardiner, Fergus William; Zhai, Shaun

2016-12-01

This study was aimed at determining the extent to which after-hours diagnostic imaging is appropriate within the case hospital's Emergency Department. This was amid growing concerns of the inappropriateness of some medical investigations within the Australian health-care system. After-hours referral data and patient notes were used in reviewing the clinical case. Diagnostic imaging was deemed appropriate if reflective of clinical guidelines, and if not reflective, whether the investigation changed the patient's ongoing management. Results indicated that 96.37% of after-hours diagnostic imaging adhered to clinical guidelines and was appropriately requested, with 95.85% changing the ongoing management of the patient. The most sought after diagnostic imaging procedures were Chest X-Ray (30.83%), and CT Brain (16.58%), with 99.16% and 98.44 appropriateness respectively. Chest pain (14.49%) and motor vehicle accidents (8.12%) were the leading reason for ordering after-hours imaging. This study provided an Emergency Department example as it relates to after-hours diagnostic imaging appropriateness. This study found that most after-hours referrals were appropriate.

Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review.

PubMed

Cargnin, Sarah; Jommi, Claudio; Canonico, Pier Luigi; Genazzani, Armando A; Terrazzino, Salvatore

2014-05-01

To determine diagnostic accuracy of HLA-B*57:01 testing for prediction of abacavir-induced hypersensitivity and to quantify the clinical benefit of pretreatment screening through a meta-analytic review of published studies. A comprehensive search was performed up to June 2013. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. The pooled diagnostic estimates were calculated using a random effect model. Despite the presence of heterogeneity in sensitivity or specificity estimates, the pooled diagnostic odds ratio to detect abacavir-induced hypersensitivity on the basis of clinical criteria was 33.07 (95% CI: 22.33-48.97, I(2): 13.9%), while diagnostic odds ratio for detection of immunologically confirmed abacavir hypersensitivity was 1141 (95% CI: 409-3181, I(2): 0%). Pooled analysis of risk ratio showed that prospective HLA-B*57:01 testing significantly reduced the incidence of abacavir-induced hypersensitivity. This meta-analysis demonstrates an excellent diagnostic accuracy of HLA-B*57:01 testing to detect immunologically confirmed abacavir hypersensitivity and corroborates existing recommendations.

[Has high-definition spiral computed tomography changed the management of patients with acute pulmonary embolism?].

PubMed

Pesavento, Raffaele; de Conti, Giorgio; Minotto, Isabella; Prandoni, Paolo

2008-12-01

Pulmonary embolism (PE) is a common condition carrying a significant degree of mortality if not diagnosed early. The diagnosis of PE is challenging, because of the non-specific nature of its clinical features. For many years the diagnostic strategies for PE have mainly involved ventilation/perfusion lung scan as the chief diagnostic procedure, often associated with a few clinical models of pre-test probability and the D-dimer test. These modalities of diagnosing PE, though quite satisfactory in various clinical settings, show several limitations, the most important one being the high rate of non-diagnostic procedures. The introduction of computed tomography (CT) has changed the diagnostic strategies and has become the main diagnostic procedure for diagnosing PE. CT is undergoing a rapid technological upgrade, which will open in the near future new frontiers in the diagnosis of PE. Nonetheless, CT carries a number of limitations, which should be carefully identified. This article reviews the evidences on both the traditional and newer diagnostic strategies for PE, outlines their strengths and weaknesses and describes future applications of CT for diagnosing PE.

The Quantitative Science of Evaluating Imaging Evidence.

PubMed

Genders, Tessa S S; Ferket, Bart S; Hunink, M G Myriam

2017-03-01

Cardiovascular diagnostic imaging tests are increasingly used in everyday clinical practice, but are often imperfect, just like any other diagnostic test. The performance of a cardiovascular diagnostic imaging test is usually expressed in terms of sensitivity and specificity compared with the reference standard (gold standard) for diagnosing the disease. However, evidence-based application of a diagnostic test also requires knowledge about the pre-test probability of disease, the benefit of making a correct diagnosis, the harm caused by false-positive imaging test results, and potential adverse effects of performing the test itself. To assist in clinical decision making regarding appropriate use of cardiovascular diagnostic imaging tests, we reviewed quantitative concepts related to diagnostic performance (e.g., sensitivity, specificity, predictive values, likelihood ratios), as well as possible biases and solutions in diagnostic performance studies, Bayesian principles, and the threshold approach to decision making. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[THE VIRTUAL CYTOLOGIC SLIDES FOR EXTERNAL EVALUATION OF QUALITY OF IMPLEMENTATION OF CYTOLOGIC ANALYSES IN CLINICAL DIAGNOSTIC LABORATORIES: POSSIBILITIES AND PERSPECTIVES].

PubMed

Djangirova, T V; Shabalova, I P; Pronichev, A N; Polyakov, E V

2015-08-01

The article considers application of technology of analysis of cytological slides in external quality control of clinical diagnostic laboratories. The advantages of virtual slides are demonstrated against other applied technologies of external evaluation of quality i.e. slide plate and digital micro-photography. The conditions of formation of virtual slides for external evaluation of quality of clinical diagnostic laboratories. The technology of their application is described. The success of practical application of considered technology in the Federal system of external evaluation of quality is emphasized.

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

PubMed Central

Pennell, Nathan A.

2017-01-01

Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice. PMID:29057238

Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy.

PubMed

Schliesser, Joshua A; Gallimore, Gary; Kunjukunju, Nancy; Sabates, Nelson R; Koulen, Peter; Sabates, Felix N

2014-01-01

While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

Use of diagnostic imaging in the emergency department for cervical spine injuries in Kingston, Ontario.

PubMed

Pickett, William; Kukaswadia, Atif; Thompson, Wendy; Frechette, Mylene; McFaull, Steven; Dowdall, Hilary; Brison, Robert J

2014-01-01

This study assessed the use and clinical yield of diagnostic imaging (radiography, computed tomography, and medical resonance imaging) ordered to assist in the diagnosis of acute neck injuries presenting to emergency departments (EDs) in Kingston, Ontario, from 2002-2003 to 2009-2010. Acute neck injury cases were identified using records from the Kingston sites of the Canadian National Ambulatory Care Reporting System. Use of radiography was analyzed over time and related to proportions of cases diagnosed with clinically significant cervical spine injuries. A total of 4,712 neck injury cases were identified. Proportions of cases referred for diagnostic imaging to the neck varied significantly over time, from 30.4% in 2002-2003 to 37.6% in 2009-2010 (ptrend  =  0.02). The percentage of total cases that were positive for clinically significant cervical spine injury ("clinical yield") also varied from a low of 5.8% in 2005-2006 to 9.2% in 2008-2009 (ptrend  =  0.04), although the clinical yield of neck-imaged cases did not increase across the study years (ptrend  =  0.23). Increased clinical yield was not observed in association with higher neck imaging rates whether that yield was expressed as a percentage of total cases positive for clinically significant injury (p  =  0.29) or as a percentage of neck-imaged cases that were positive (p  =  0.77). We observed increases in the use of diagnostic images over time, reflecting a need to reinforce an existing clinical decision rule for cervical spine radiography. Temporal increases in the clinical yield for total cases may suggest a changing case mix or more judicious use of advanced types of diagnostic imaging.

Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn’s Disease Patients: Results from the CONNECT Study

PubMed Central

Moon, Chang Mo; Jung, Sung-Ae; Kim, Seong-Eun; Song, Hyun Joo; Jung, Yunho; Ye, Byong Duk; Cheon, Jae Hee; Kim, You Sun; Kim, Young-Ho; Kim, Joo Sung; Han, Dong Soo

2015-01-01

Diagnostic delay frequently occurs in Crohn’s disease (CD) patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn’s Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years) (p = 0.014), concomitant upper gastrointestinal (UGI) disease (p = 0.012) and penetrating disease behavior at diagnosis (p = 0.001) were positively associated with long diagnostic delay (≥18 months). During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07–1.93; p = 0.017), internal fistulas (HR, 1.62; 95% CI, 1.12–2.33; p = 0.011), and perianal fistulas (HR, 1.38; 95% CI, 1.06–1.80; p = 0.016). However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas. PMID:26647084

Genetic variation of iron-induced uroporphyria in mice.

PubMed Central

Smith, A G; Francis, J E

1993-01-01

Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase (UROD) and uroporphyria in C57BL/10ScSn but not DBA/2 mice [Smith, Cabral, Carthew, Francis and Manson (1989) Int. J. Cancer 43, 492-496]. We have investigated the induction of uroporphyria in 12 inbred strains of mice 25 weeks after iron treatment (600 mg/kg) to determine if there was any correlation with the Ah locus. Under these conditions, inhibition of UROD occurred to varying degrees in Ahd mice (SWR and AKR) as well as nominally Ahb-1 (C57BL/6J, C57BL/10ScSn and C57BL/10-cc) and Ahb-2 strains (BALB/c and C3H/HeJ). Five other Ahb or Ahd strains (C57BL/Ks, A/J, CBA/J, LP and DBA/2) were unaffected. Thus there appeared to be no correlation with the Ah phenotype and this illustrated that some other variable inherited factors are involved. Comparisons between another susceptible strain, A2G, and the congenic A2G-hr/+strain (carrying the recessive hr gene) showed a modulating influence associated with the hr locus. In contrast with individual mice of inbred strains, which showed consistent responses to iron, those of the outbred MF1 strain showed a spectrum of sensitivities as might be expected for a heterogeneic stock. The rate of porphyria development was accelerated by administration of 5-aminolaevulinic acid (5-ALA) in the drinking water, but this did not overcome strain differences. Among four strains the order of susceptibility was SWR > C57BL/10ScSn > C57B1/6J > DBA/2 (the last strain was completely resistant). With degrees of iron loading greater than 600 mg of Fe/kg (1200-1800 mg of Fe/kg) C57BL/10ScSn mice (after 20 weeks) and SWR mice (after 5 weeks which included 4 weeks of 5-ALA treatment) had less inhibition of UROD and a lower uroporphyric response, showing that there was an optimum level of liver iron concentration. Studies on selected microsomal enzyme activities associated with cytochrome P-450 showed no correlation with the propensities of strains to develop porphyria. These activities included the NADPH-dependent oxidation of uroporphyrinogen I to uroporphyrin I. PMID:8471047

Horizon 2020 SME-Instrument topic: clinical research for the validation of biomarkers and/or diagnostic medical devices.

PubMed

Sanne, Jean-Luc

2018-06-21

The European Commission released €130 million over 2014, 2015 and 2017 under the EU Framework Program for Research and Innovation, Horizon 2020, to support innovative small and medium-sized enterprises in the diagnostic area. The call topic focused on 'Clinical research for the validation of biomarkers and/or diagnostic medical devices'. It attracted 1194 applicants from all over Europe. The quality of the proposals was high and a large proportion of them were eligible for funding. In the majority, proposals were about in vitro diagnostics and tackled both clinical validation of new biomarkers and device optimization. The proposals dealt with various advanced technologies. One third of the proposers gave priority to the new and promising field of personalized medicine.

Impact of molecular imaging on the diagnostic process in a memory clinic.

PubMed

Ossenkoppele, Rik; Prins, Niels D; Pijnenburg, Yolande A L; Lemstra, Afina W; van der Flier, Wiesje M; Adriaanse, Sofie F; Windhorst, Albert D; Handels, Ron L H; Wolfs, Claire A G; Aalten, Pauline; Verhey, Frans R J; Verbeek, Marcel M; van Buchem, Mark A; Hoekstra, Otto S; Lammertsma, Adriaan A; Scheltens, Philip; van Berckel, Bart N M

2013-07-01

[(11)C]Pittsburgh compound B ([(11)C]PIB) and [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) PET measure fibrillar amyloid-β load and glucose metabolism, respectively. We evaluated the impact of these tracers on the diagnostic process in a memory clinic population. One hundred fifty-four patients underwent paired dynamic [(11)C]PIB and static [(18)F]FDG PET scans shortly after completing a standard dementia screening. Two-year clinical follow-up data were available for 39 patients. Parametric PET images were assessed visually and results were reported to the neurologists responsible for the initial diagnosis. Outcome measures were (change in) clinical diagnosis and confidence in that diagnosis before and after disclosing PET results. [(11)C]PIB scans were positive in 40 of 66 (61%) patients with a clinical diagnosis of Alzheimer's disease (AD), 5 of 18 (28%) patients with frontotemporal dementia (FTD), 4 of 5 (80%) patients with Lewy body dementia, and 3 of 10 (30%) patients with other dementias. [(18)F]FDG uptake patterns matched the clinical diagnosis in 38 of 66 (58%) of AD patients, and in 6 of 18 (33%) FTD patients. PET results led to a change in diagnosis in 35 (23%) patients. This only occurred when prior diagnostic certainty was <90%. Diagnostic confidence increased from 71 ± 17% before to 87 ± 16% after PET (p < .001). Two-year clinical follow-up (n = 39) showed that [(11)C]PIB and [(18)F]FDG predicted progression to AD for patients with mild cognitive impairment, and that the diagnosis of dementia established after PET remained unchanged in 96% of patients. In a memory clinic setting, combined [(11)C]PIB and [(18)F]FDG PET are of additional value on top of the standard diagnostic work-up, especially when prior diagnostic confidence is low. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Should we confirm our clinical diagnostic certainty by autopsies?

PubMed

Podbregar, M; Voga, G; Krivec, B; Skale, R; Pareznik, R; Gabrscek, L

2001-11-01

To evaluate the frequency of diagnostic errors assessed by autopsies. Retrospective review of medical and pathological records in an 11-bed closed medical intensive care unit (ICU) at a 860-bed general hospital. Patients who died in the ICU between January 1998 and December 1999. Medical diagnoses were rated into three levels of clinical diagnostic certainty: complete certainty (group L1), minor diagnostic uncertainty (group L2), and major diagnostic uncertainty (group L3). The patients were divided into three error groups: group A, the autopsy confirmed the clinical diagnosis; group B, the autopsy demonstrated a new relevant diagnosis which would probably not have influenced the therapy and outcome; group C, the autopsy demonstrated a new relevant diagnosis which would probably have changed the therapy and outcome. The overall mortality was 20.3% (270/1331 patients). Autopsies were performed in 126 patients (46.9% of deaths), more often in younger patients (66.6+/-13.9 years vs 72.7+/-12.0 years, p<0.001), in patients with shorter ICU stay (4.7+/-5.6 days vs 6.7+/-8.7 days, p=0.054), and in patients in group L3 without chronic diseases (15/126 vs 1/144, p<0.001). Fatal but potentially treatable errors [group C, 12 patients (9.5%)] were found in 8.7%, 10.0%, and 10.5% of patients in groups L1, L2, and L3, respectively (NS between groups). An ICU length of stay shorter than 24 h was not related to the frequency of group C errors. Autopsies are performed more often in younger patients without chronic disease and in patients with a low clinical diagnostic certainty. No level of clinical diagnostic certainty could predict the pathological findings.

Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges

PubMed Central

2013-01-01

Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant. PMID:24088261

Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

PubMed

Maeda, Akiko; Yoshida, Akiko; Kawai, Kanako; Arai, Yuki; Akiba, Ryutaro; Inaba, Akira; Takagi, Seiji; Fujiki, Ryoji; Hirami, Yasuhiko; Kurimoto, Yasuo; Ohara, Osamu; Takahashi, Masayo

2018-05-21

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. Evaluation of diagnostic technology, Prospective, Clinical and experimental study. A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group.

PubMed

Tsalik, Ephraim L; Petzold, Elizabeth; Kreiswirth, Barry N; Bonomo, Robert A; Banerjee, Ritu; Lautenbach, Ebbing; Evans, Scott R; Hanson, Kimberly E; Klausner, Jeffrey D; Patel, Robin

2017-03-15

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

High-throughput cell analysis and sorting technologies for clinical diagnostics and therapeutics

NASA Astrophysics Data System (ADS)

Leary, James F.; Reece, Lisa M.; Szaniszlo, Peter; Prow, Tarl W.; Wang, Nan

2001-05-01

A number of theoretical and practical limits of high-speed flow cytometry/cell sorting are important for clinical diagnostics and therapeutics. Three applications include: (1) stem cell isolation with tumor purging for minimal residual disease monitoring and treatment, (2) identification and isolation of human fetal cells from maternal blood for prenatal diagnostics and in-vitro therapeutics, and (3) high-speed library screening for recombinant vaccine production against unknown pathogens.

Multidimensional Diagnostic Criteria for Chronic Pain: Introduction to the ACTTION-American Pain Society Pain Taxonomy (AAPT).

PubMed

Dworkin, Robert H; Bruehl, Stephen; Fillingim, Roger B; Loeser, John D; Terman, Gregory W; Turk, Dennis C

2016-09-01

A variety of approaches have been used to develop diagnostic criteria for chronic pain. The published evidence of the reliability and validity of existing diagnostic criteria is limited, and these criteria have typically not been used in clinical practice. The availability of a widely accepted, consistently applied, and evidence-based taxonomy of diagnostic criteria would improve the quality of clinical research on chronic pain and would be of great value in clinical practice. To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS) have collaborated on the development of the ACTTION-APS Pain Taxonomy (AAPT). AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. This article (1) describes the background and rationale for AAPT; (2) presents the AAPT taxonomy and the specific conditions for which diagnostic criteria have been developed (to be published separately); (3) briefly reviews the 5 dimensions that constitute the AAPT multidimensional framework and describes the 7 accompanying articles that discuss these dimensions and other important issues involving AAPT; and (4) provides an overview of next steps, specifically, the general processes by which the initial set of diagnostic criteria (for which the evidence base has been drawn from the literature, systematic reviews, and secondary analyses of existing databases) will undergo additional assessments of reliability and validity. To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. The long-term objective of AAPT is to advance the scientific understanding of chronic pain and its treatment. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

How do clinicians actually use the Diagnostic and Statistical Manual of Mental Disorders in clinical practice and why we need to know more.

PubMed

First, Michael B; Bhat, Venkat; Adler, David; Dixon, Lisa; Goldman, Beth; Koh, Steve; Levine, Bruce; Oslin, David; Siris, Sam

2014-12-01

The clinical use of the Diagnostic and Statistical Manual of Mental Disorders (DSM) is explicitly stated as a goal for both the DSM Fourth Edition and DSM Fifth Edition (DSM-5) revisions. Many uses assume a relatively faithful application of the DSM diagnostic definitions. However, studies demonstrate significant discrepancies between clinical psychiatric diagnoses with those made using structured interviews suggesting that clinicians do not systematically apply the diagnostic criteria. The limited information regarding how clinicians actually use the DSM raises important questions: a) How can the clinical use be improved without first having a baseline assessment? b) How can potentially significant shifts in practice patterns based on wording changes be assessed without knowing the extent to which the criteria are used as written? Given the American Psychiatric Association's plans for interim revisions to the DSM-5, the value of a detailed exploration of its actual use in clinical practice remains a significant ongoing concern and deserves further study including a number of survey and in vivo studies.

The Diagnostic Validity and Reliability of an Internet-Based Clinical Assessment Program for Mental Disorders

PubMed Central

Klein, Britt; Meyer, Denny; Austin, David William; Abbott, Jo-Anne M

2015-01-01

Background Internet-based assessment has the potential to assist with the diagnosis of mental health disorders and overcome the barriers associated with traditional services (eg, cost, stigma, distance). Further to existing online screening programs available, there is an opportunity to deliver more comprehensive and accurate diagnostic tools to supplement the assessment and treatment of mental health disorders. Objective The aim was to evaluate the diagnostic criterion validity and test-retest reliability of the electronic Psychological Assessment System (e-PASS), an online, self-report, multidisorder, clinical assessment and referral system. Methods Participants were 616 adults residing in Australia, recruited online, and representing prospective e-PASS users. Following e-PASS completion, 158 participants underwent a telephone-administered structured clinical interview and 39 participants repeated the e-PASS within 25 days of initial completion. Results With structured clinical interview results serving as the gold standard, diagnostic agreement with the e-PASS varied considerably from fair (eg, generalized anxiety disorder: κ=.37) to strong (eg, panic disorder: κ=.62). Although the e-PASS’ sensitivity also varied (0.43-0.86) the specificity was generally high (0.68-1.00). The e-PASS sensitivity generally improved when reducing the e-PASS threshold to a subclinical result. Test-retest reliability ranged from moderate (eg, specific phobia: κ=.54) to substantial (eg, bulimia nervosa: κ=.87). Conclusions The e-PASS produces reliable diagnostic results and performs generally well in excluding mental disorders, although at the expense of sensitivity. For screening purposes, the e-PASS subclinical result generally appears better than a clinical result as a diagnostic indicator. Further development and evaluation is needed to support the use of online diagnostic assessment programs for mental disorders. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG). PMID:26392066

Developing a science of clinical utility in diagnostic classification systems field study strategies for ICD-11 mental and behavioral disorders.

PubMed

Keeley, Jared W; Reed, Geoffrey M; Roberts, Michael C; Evans, Spencer C; Medina-Mora, María Elena; Robles, Rebeca; Rebello, Tahilia; Sharan, Pratap; Gureje, Oye; First, Michael B; Andrews, Howard F; Ayuso-Mateos, José Luís; Gaebel, Wolfgang; Zielasek, Juergen; Saxena, Shekhar

2016-01-01

The World Health Organization (WHO) Department of Mental Health and Substance Abuse has developed a systematic program of field studies to evaluate and improve the clinical utility of the proposed diagnostic guidelines for mental and behavioral disorders in the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11). The clinical utility of a diagnostic classification is critical to its function as the interface between health encounters and health information, and to making the ICD-11 be a more effective tool for helping the WHO's 194 member countries, including the United States, reduce the global disease burden of mental disorders. This article describes the WHO's efforts to develop a science of clinical utility in regard to one of the two major classification systems for mental disorders. We present the rationale and methodologies for an integrated and complementary set of field study strategies, including large international surveys, formative field studies of the structure of clinicians' conceptualization of mental disorders, case-controlled field studies using experimental methodologies to evaluate the impact of proposed changes to the diagnostic guidelines on clinicians' diagnostic decision making, and ecological implementation field studies of clinical utility in the global settings in which the guidelines will ultimately be implemented. The results of these studies have already been used in making decisions about the structure and content of ICD-11. If clinical utility is indeed among the highest aims of diagnostic systems for mental disorders, as their developers routinely claim, future revision efforts should continue to build on these efforts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Toward a Framework for Benefit-Risk Assessment in Diagnostic Imaging: Identifying Scenario-specific Criteria.

PubMed

Agapova, Maria; Bresnahan, Brian W; Linnau, Ken F; Garrison, Louis P; Higashi, Mitchell; Kessler, Larry; Devine, Beth

2017-05-01

Diagnostic imaging has many effects and there is no common definition of value in diagnostic radiology. As benefit-risk trade-offs are rarely made explicit, it is not clear which framework is used in clinical guideline development. We describe initial steps toward the creation of a benefit-risk framework for diagnostic radiology. We performed a literature search and an online survey of physicians to identify and collect benefit-risk criteria (BRC) relevant to diagnostic imaging tests. We operationalized a process for selection of BRC with the use of four clinical use case scenarios that vary by diagnostic alternatives and clinical indication. Respondent BRC selections were compared across clinical scenarios and between radiologists and nonradiologists. Thirty-six BRC were identified and organized into three domains: (1) those that account for differences attributable only to the test or device (n = 17); (2) those that account for clinical management and provider experiences (n = 12); and (3) those that capture patient experience (n = 7). Forty-eight survey participants selected 22 criteria from the initial list in the survey (9-11 per case). Engaging ordering physicians increased the number of criteria selected in each of the four clinical scenarios presented. We developed a process for standardizing selection of BRC in guideline development. These results suggest that a process relying on elements of comparative effectiveness and the use of standardized BRC may ensure consistent examination of differences among alternatives by way of making explicit implicit trade-offs that otherwise enter the decision-making space and detract from consistency and transparency. These findings also highlight the need for multidisciplinary teams that include input from ordering physicians. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Clinical reasoning in the real world is mediated by bounded rationality: implications for diagnostic clinical practice guidelines.

PubMed

Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo

2010-04-20

Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.

Clinical Reasoning in the Real World Is Mediated by Bounded Rationality: Implications for Diagnostic Clinical Practice Guidelines

PubMed Central

Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo

2010-01-01

Background Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. Method This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. Results Four main themes were identified: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Discussion Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration. PMID:20421920

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

PubMed

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-06-07

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

[Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis].

PubMed

Shin, Jung Woo; Park, Neung Hwa

2016-07-25

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology

PubMed Central

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y.-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-01-01

Abstract Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy. PMID:29850871

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.

PubMed

Sharma, Shikha; Zapatero-Rodríguez, Julia; O'Kennedy, Richard

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare. Copyright © 2016. Published by Elsevier Inc.

Screening pregnant women for suicidal behavior in electronic medical records: diagnostic codes vs. clinical notes processed by natural language processing.

PubMed

Zhong, Qiu-Yue; Karlson, Elizabeth W; Gelaye, Bizu; Finan, Sean; Avillach, Paul; Smoller, Jordan W; Cai, Tianxi; Williams, Michelle A

2018-05-29

We examined the comparative performance of structured, diagnostic codes vs. natural language processing (NLP) of unstructured text for screening suicidal behavior among pregnant women in electronic medical records (EMRs). Women aged 10-64 years with at least one diagnostic code related to pregnancy or delivery (N = 275,843) from Partners HealthCare were included as our "datamart." Diagnostic codes related to suicidal behavior were applied to the datamart to screen women for suicidal behavior. Among women without any diagnostic codes related to suicidal behavior (n = 273,410), 5880 women were randomly sampled, of whom 1120 had at least one mention of terms related to suicidal behavior in clinical notes. NLP was then used to process clinical notes for the 1120 women. Chart reviews were performed for subsamples of women. Using diagnostic codes, 196 pregnant women were screened positive for suicidal behavior, among whom 149 (76%) had confirmed suicidal behavior by chart review. Using NLP among those without diagnostic codes, 486 pregnant women were screened positive for suicidal behavior, among whom 146 (30%) had confirmed suicidal behavior by chart review. The use of NLP substantially improves the sensitivity of screening suicidal behavior in EMRs. However, the prevalence of confirmed suicidal behavior was lower among women who did not have diagnostic codes for suicidal behavior but screened positive by NLP. NLP should be used together with diagnostic codes for future EMR-based phenotyping studies for suicidal behavior.

Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

PubMed

Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

2009-02-01

With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies.

PubMed

Fàbregas, N; Ewig, S; Torres, A; El-Ebiary, M; Ramirez, J; de La Bellacasa, J P; Bauer, T; Cabello, H

1999-10-01

A study was undertaken to assess the diagnostic value of different clinical criteria and the impact of microbiological testing on the accuracy of clinical diagnosis of suspected ventilator associated pneumonia (VAP). Twenty five deceased mechanically ventilated patients were studied prospectively. Immediately after death, multiple bilateral lung biopsy specimens (16 specimens/patient) were obtained for histological examination and quantitative lung cultures. The presence of both histological pneumonia and positive lung cultures was used as a reference test. The presence of infiltrates on the chest radiograph and two of three clinical criteria (leucocytosis, purulent secretions, fever) had a sensitivity of 69% and a specificity of 75%; the corresponding numbers for the clinical pulmonary infection score (CPIS) were 77% and 42%. Non-invasive as well as invasive sampling techniques had comparable values. The combination of all techniques achieved a sensitivity of 85% and a specificity of 50%, and these values remained virtually unchanged despite the presence of previous treatment with antibiotics. When microbiological results were added to clinical criteria, adequate diagnoses originating from microbiological results which might have corrected false positive and false negative clinical judgements (n = 5) were countered by a similar proportion of inadequate diagnoses (n = 6). Clinical criteria had reasonable diagnostic values. CPIS was not superior to conventional clinical criteria. Non-invasive and invasive sampling techniques had diagnostic values comparable to clinical criteria. An algorithm guiding antibiotic treatment exclusively by microbiological results does not increase the overall diagnostic accuracy and carries the risk of undertreatment.

Important clinical descriptors to include in the examination and assessment of patients with femoroacetabular impingement syndrome: an international and multi-disciplinary Delphi survey.

PubMed

Reiman, M P; Thorborg, K; Covington, K; Cook, C E; Hölmich, P

2017-06-01

Determine which examination findings are key clinical descriptors of femoroacetabular impingement syndrome (FAIS) through use of an international, multi-disciplinary expert panel. A three-round Delphi survey utilizing an international, multi-disciplinary expert panel operationally defined from international publications and presentations was utilized. All six domains (subjective examination, patient-reported outcome measures, physical examination, special tests, physical performance measures, and diagnostic imaging) had at least one descriptor with 75% consensus agreement for diagnosis and assessment of FAIS. Diagnostic imaging was the domain with the highest level of agreement. Domains such as patient-reported outcome measures (PRO's) and physical examination were identified as non-diagnostic measures (rather as assessments of disease impact). Although it also had the greatest level of variability in description of examination domains, diagnostic imaging continues to be the preeminent diagnostic measure for FAIS. No single domain should be utilized as the sole diagnostic or assessment parameter for FAIS. While not all investigated domains provide diagnostic capability for FAIS, those that do not are able to serve purpose as a measure of disease impact (e.g., impairments and activity limitations). The clinical relevance of this Delphi survey is the understanding that a comprehensive assessment measuring both diagnostic capability and disease impact most accurately reflects the patient with FAIS. V.

A new condition for assessing the clinical efficiency of a diagnostic test.

PubMed

Bokhari, Ehsan; Hubert, Lawrence

2015-09-01

When prediction using a diagnostic test outperforms simple prediction using base rates, the test is said to be "clinically efficient," a term first introduced into the literature by Meehl and Rosen (1955) in Psychological Bulletin. This article provides three equivalent conditions for determining the clinical efficiency of a diagnostic test: (a) Meehl-Rosen (Meehl & Rosen, 1955); (b) Dawes (Dawes, 1962); and (c) the Bokhari-Hubert condition, introduced here for the first time. Clinical efficiency is then generalized to situations where misclassification costs are considered unequal (for example, false negatives are more costly than false positives). As an illustration, the clinical efficiency of an actuarial device for predicting violent and dangerous behavior is examined that was developed as part of the MacArthur Violence Risk Assessment Study. (c) 2015 APA, all rights reserved.

En Route to the Clinic: Diagnostic Sequencing Applications Using the Ion Torrent (7th Annual SFAF Meeting, 2012)

ScienceCinema

Muzny, Donna

2018-01-15

Donna Muzny on "En route to the clinic: Diagnostic sequencing applications using the Ion Torrent" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary.

PubMed

Moran, Sebastián; Martinez-Cardús, Anna; Boussios, Stergios; Esteller, Manel

2017-11-01

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

Feasibility, acceptability and clinical utility of the Cultural Formulation Interview: mixed-methods results from the DSM-5 international field trial.

PubMed

Lewis-Fernández, Roberto; Aggarwal, Neil Krishan; Lam, Peter C; Galfalvy, Hanga; Weiss, Mitchell G; Kirmayer, Laurence J; Paralikar, Vasudeo; Deshpande, Smita N; Díaz, Esperanza; Nicasio, Andel V; Boiler, Marit; Alarcón, Renato D; Rohlof, Hans; Groen, Simon; van Dijk, Rob C J; Jadhav, Sushrut; Sarmukaddam, Sanjeev; Ndetei, David; Scalco, Monica Z; Bassiri, Kavoos; Aguilar-Gaxiola, Sergio; Ton, Hendry; Westermeyer, Joseph; Vega-Dienstmaier, Johann M

2017-04-01

Background There is a need for clinical tools to identify cultural issues in diagnostic assessment. Aims To assess the feasibility, acceptability and clinical utility of the DSM-5 Cultural Formulation Interview (CFI) in routine clinical practice. Method Mixed-methods evaluation of field trial data from six countries. The CFI was administered to diagnostically diverse psychiatric out-patients during a diagnostic interview. In post-evaluation sessions, patients and clinicians completed debriefing qualitative interviews and Likert-scale questionnaires. The duration of CFI administration and the full diagnostic session were monitored. Results Mixed-methods data from 318 patients and 75 clinicians found the CFI feasible, acceptable and useful. Clinician feasibility ratings were significantly lower than patient ratings and other clinician-assessed outcomes. After administering one CFI, however, clinician feasibility ratings improved significantly and subsequent interviews required less time. Conclusions The CFI was included in DSM-5 as a feasible, acceptable and useful cultural assessment tool. © The Royal College of Psychiatrists 2017.

The impact of extended longitudinal observation on the assessment of personality disorders.

PubMed

Pedersen, G; Karterud, S; Hummelen, B; Wilberg, T

2013-11-01

Multiple sources of information are necessary for a valid assessment of personality disorders (PDs). This study investigates the impact of longitudinal observation. The sample comprised 1217 patients from 15 different treatment units. PDs were assessed at admission to treatment using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) and additional clinical information (best estimate diagnosis). After approximately 18 weeks of treatment, the SCID-II protocols were re-examined at clinical conferences and the diagnostic status reassessed on the basis of longitudinal observations in multiple group situations (longitudinal, expert, all data principle). Using this procedure, 78% of the patients' diagnostic criteria sets were changed, and 32% of patients' diagnostic statuses were changed. Many (32%) patients who were evaluated initially as not having a PD received a PD diagnosis after re-examination. The information provided by customary clinical assessment has important limitations, and longitudinal observation provides additional information that may change the diagnostic status in approximately one-third of PD cases. Copyright © 2013 John Wiley & Sons, Ltd.

Evaluating a mobile application for improving clinical laboratory test ordering and diagnosis.

PubMed

Meyer, Ashley N D; Thompson, Pamela J; Khanna, Arushi; Desai, Samir; Mathews, Benji K; Yousef, Elham; Kusnoor, Anita V; Singh, Hardeep

2018-04-20

Mobile applications for improving diagnostic decision making often lack clinical evaluation. We evaluated if a mobile application improves generalist physicians' appropriate laboratory test ordering and diagnosis decisions and assessed if physicians perceive it as useful for learning. In an experimental, vignette study, physicians diagnosed 8 patient vignettes with normal prothrombin times (PT) and abnormal partial thromboplastin times (PTT). Physicians made test ordering and diagnosis decisions for 4 vignettes using each resource: a mobile app, PTT Advisor, developed by the Centers for Disease Control and Prevention (CDC)'s Clinical Laboratory Integration into Healthcare Collaborative (CLIHC); and usual clinical decision support. Then, physicians answered questions regarding their perceptions of the app's usefulness for diagnostic decision making and learning using a modified Kirkpatrick Training Evaluation Framework. Data from 368 vignettes solved by 46 physicians at 7 US health care institutions show advantages for using PTT Advisor over usual clinical decision support on test ordering and diagnostic decision accuracy (82.6 vs 70.2% correct; P < .001), confidence in decisions (7.5 vs 6.3 out of 10; P < .001), and vignette completion time (3:02 vs 3:53 min.; P = .06). Physicians reported positive perceptions of the app's potential for improved clinical decision making, and recommended it be used to address broader diagnostic challenges. A mobile app, PTT Advisor, may contribute to better test ordering and diagnosis, serve as a learning tool for diagnostic evaluation of certain clinical disorders, and improve patient outcomes. Similar methods could be useful for evaluating apps aimed at improving testing and diagnosis for other conditions.

Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience.

PubMed

Hu, Xuyun; Li, Niu; Xu, Yufei; Li, Guoqiang; Yu, Tingting; Yao, Ru-En; Fu, Lijun; Wang, Jiwen; Yin, Lei; Yin, Yong; Wang, Ying; Jin, Xingming; Wang, Xiumin; Wang, Jian; Shen, Yiping

2017-11-02

PurposeTo evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions.MethodsA total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire.ResultsPOMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case.ConclusionWe adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.195.

Developing a modular architecture for creation of rule-based clinical diagnostic criteria.

PubMed

Hong, Na; Pathak, Jyotishman; Chute, Christopher G; Jiang, Guoqian

2016-01-01

With recent advances in computerized patient records system, there is an urgent need for producing computable and standards-based clinical diagnostic criteria. Notably, constructing rule-based clinical diagnosis criteria has become one of the goals in the International Classification of Diseases (ICD)-11 revision. However, few studies have been done in building a unified architecture to support the need for diagnostic criteria computerization. In this study, we present a modular architecture for enabling the creation of rule-based clinical diagnostic criteria leveraging Semantic Web technologies. The architecture consists of two modules: an authoring module that utilizes a standards-based information model and a translation module that leverages Semantic Web Rule Language (SWRL). In a prototype implementation, we created a diagnostic criteria upper ontology (DCUO) that integrates ICD-11 content model with the Quality Data Model (QDM). Using the DCUO, we developed a transformation tool that converts QDM-based diagnostic criteria into Semantic Web Rule Language (SWRL) representation. We evaluated the domain coverage of the upper ontology model using randomly selected diagnostic criteria from broad domains (n = 20). We also tested the transformation algorithms using 6 QDM templates for ontology population and 15 QDM-based criteria data for rule generation. As the results, the first draft of DCUO contains 14 root classes, 21 subclasses, 6 object properties and 1 data property. Investigation Findings, and Signs and Symptoms are the two most commonly used element types. All 6 HQMF templates are successfully parsed and populated into their corresponding domain specific ontologies and 14 rules (93.3 %) passed the rule validation. Our efforts in developing and prototyping a modular architecture provide useful insight into how to build a scalable solution to support diagnostic criteria representation and computerization.

Clinical data miner: an electronic case report form system with integrated data preprocessing and machine-learning libraries supporting clinical diagnostic model research.

PubMed

Installé, Arnaud Jf; Van den Bosch, Thierry; De Moor, Bart; Timmerman, Dirk

2014-10-20

Using machine-learning techniques, clinical diagnostic model research extracts diagnostic models from patient data. Traditionally, patient data are often collected using electronic Case Report Form (eCRF) systems, while mathematical software is used for analyzing these data using machine-learning techniques. Due to the lack of integration between eCRF systems and mathematical software, extracting diagnostic models is a complex, error-prone process. Moreover, due to the complexity of this process, it is usually only performed once, after a predetermined number of data points have been collected, without insight into the predictive performance of the resulting models. The objective of the study of Clinical Data Miner (CDM) software framework is to offer an eCRF system with integrated data preprocessing and machine-learning libraries, improving efficiency of the clinical diagnostic model research workflow, and to enable optimization of patient inclusion numbers through study performance monitoring. The CDM software framework was developed using a test-driven development (TDD) approach, to ensure high software quality. Architecturally, CDM's design is split over a number of modules, to ensure future extendability. The TDD approach has enabled us to deliver high software quality. CDM's eCRF Web interface is in active use by the studies of the International Endometrial Tumor Analysis consortium, with over 4000 enrolled patients, and more studies planned. Additionally, a derived user interface has been used in six separate interrater agreement studies. CDM's integrated data preprocessing and machine-learning libraries simplify some otherwise manual and error-prone steps in the clinical diagnostic model research workflow. Furthermore, CDM's libraries provide study coordinators with a method to monitor a study's predictive performance as patient inclusions increase. To our knowledge, CDM is the only eCRF system integrating data preprocessing and machine-learning libraries. This integration improves the efficiency of the clinical diagnostic model research workflow. Moreover, by simplifying the generation of learning curves, CDM enables study coordinators to assess more accurately when data collection can be terminated, resulting in better models or lower patient recruitment costs.

Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward

PubMed Central

Twisk, Frank N.M.

2016-01-01

Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight “additional” symptoms. The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the “diagnostic impasse” the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS. However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues. Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS. Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current “diagnostic impasse”. PMID:26861399

Autism in the Faroe Islands: Diagnostic Stability from Childhood to Early Adult Life

PubMed Central

Kočovská, Eva; Billstedt, Eva; Ellefsen, Asa; Kampmann, Hanna; Gillberg, I. Carina; Biskupstø, Rannvá; Andorsdóttir, Guðrið; Stóra, Tormóður; Minnis, Helen; Gillberg, Christopher

2013-01-01

Childhood autism or autism spectrum disorder (ASD) has been regarded as one of the most stable diagnostic categories applied to young children with psychiatric/developmental disorders. The stability over time of a diagnosis of ASD is theoretically interesting and important for various diagnostic and clinical reasons. We studied the diagnostic stability of ASD from childhood to early adulthood in the Faroe Islands: a total school age population sample (8–17-year-olds) was screened and diagnostically assessed for AD in 2002 and 2009. This paper compares both independent clinical diagnosis and Diagnostic Interview for Social and Communication Disorders (DISCO) algorithm diagnosis at two time points, separated by seven years. The stability of clinical ASD diagnosis was perfect for AD, good for “atypical autism”/PDD-NOS, and less than perfect for Asperger syndrome (AS). Stability of the DISCO algorithm subcategory diagnoses was more variable but still good for AD. Both systems showed excellent stability over the seven-year period for “any ASD” diagnosis, although a number of clear cases had been missed at the original screening in 2002. The findings support the notion that subcategories of ASD should be collapsed into one overarching diagnostic entity with subgrouping achieved on other “non-autism” variables, such as IQ and language levels and overall adaptive functioning. PMID:23476144

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.

PubMed

Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P

2017-09-01

Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

PubMed Central

Vissers, Lisenka E.L.M.; van Nimwegen, Kirsten J.M.; Schieving, Jolanda H.; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G.; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G.; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A.; Willemsen, Michèl A.A.P.

2017-01-01

Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously. Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin. Genet Med advance online publication 23 March 2017 PMID:28333917

Diagnostic indices for vertiginous diseases

PubMed Central

2010-01-01

Background Vertigo and dizziness are symptoms which are reported frequently in clinical practice. We aimed to develop diagnostic indices for four prevalent vertiginous diseases: benign paroxysmal positional vertigo (BPPV), Menière's disease (MD), vestibular migraine (VM), and phobic postural vertigo (PPV). Methods Based on a detailed questionnaire handed out to consecutive patients presenting for the first time in our dizziness clinic we preselected a set of seven questions with desirable diagnostic properties when compared with the final diagnosis after medical workup. Using exact logistic regression analysis diagnostic scores, each comprising of four to six items that can simply be added up, were built for each of the four diagnoses. Results Of 193 patients 131 questionnaires were left after excluding those with missing consent or data. Applying the suggested cut-off points, sensitivity and specificity were 87.5 and 93.5% for BPPV, 100 and 87.4% for MD, 92.3 and 83.7% for VM, 73.7 and 84.1% for PPV, respectively. By changing the cut-off points sensitivity and specificity can be adjusted to meet diagnostic needs. Conclusions The diagnostic indices showed promising diagnostic properties. Once further validated, they could provide an ease to use and yet flexible tool for screening vertigo in clinical practice and epidemiological research. PMID:20973968

Some Clinical Diagnoses are More Reliable than Others

DTIC Science & Technology

1989-03-29

a more reliable measure than diagnostic type (e.g., schizophrenia versus personality disor- der). Diagnostic type, in turn, was a more reliable...measure than diagnostic subtype (e.g., chronic catatonic schizophrenic). And, certain diagnostic types aild Suutypes wete consistently more reliable across...diagnoses included thie following diagnostic typesý: 1) organic psychoses, 2) schizophrenia , 3) affective psychoses, 4) pala- 4 noia, 5) other

Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria.

PubMed

Schoemakers, Rik J; Schnabel, Ronny; Oudhuis, Guy J; Linssen, Catharina F M; van Mook, Walther N K A; Verbon, Annelies; Bergmans, Dennis C J J

2014-12-01

The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.

Human rabies in India: an audit from a rabies diagnostic laboratory.

PubMed

Mani, Reeta Subramaniam; Anand, Ashwini Manoor; Madhusudana, Shampur Narayan

2016-04-01

Rabies, an acute progressive encephalomyelitis, continues to be a serious public health problem in India and many other countries in Asia and Africa. The low level of commitment to rabies control is partly attributable to challenges in laboratory diagnosis and lack of adequate surveillance to indicate the disease burden. A laboratory audit of human rabies cases was undertaken to disseminate information on the clinical, demographic, prophylactic and most importantly the laboratory diagnostic aspects of rabies. A retrospective analysis of all clinically suspected human rabies cases, whose samples were received at a rabies diagnostic laboratory in South India in the last 3 years, was performed. Clinical and demographic details of patients were obtained. The clinical samples included cerebrospinal fluid (CSF), serum, saliva and nuchal skin biopsy collected antemortem, and brain tissue obtained post-mortem. Various laboratory tests were performed for diagnosis. Clinical samples from 128 patients with suspected rabies, from 11 states in India, were received for diagnostic confirmation. About 94% of the victims reported dog-bites, more than a third of them were children and most of the victims did not receive adequate post-exposure prophylaxis. Antemortem confirmation of rabies by a combination of laboratory diagnostic assays (detection of viral RNA in CSF, skin and saliva, and neutralising antibodies in CSF) could be achieved in 40.6% cases. Increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease. © 2016 John Wiley & Sons Ltd.

Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

PubMed Central

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond H; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-01

The standard of care for first-tier clinical investigation of the aetiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion–deletions (indels) and single-nucleotide variant (SNV) mutations. Whole-genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilised WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a fourfold increase in diagnostic rate over CMA (8%; P value=1.42E−05) alone and more than twofold increase in CMA plus targeted gene sequencing (13%; P value=0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harbouring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis. PMID:28567303

Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.

PubMed

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-13

The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. Whole genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilized WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counseling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis.

Diagnostic Performance of Electronic Syndromic Surveillance Systems in Acute Care

PubMed Central

Kashiouris, M.; O’Horo, J.C.; Pickering, B.W.; Herasevich, V.

2013-01-01

Context Healthcare Electronic Syndromic Surveillance (ESS) is the systematic collection, analysis and interpretation of ongoing clinical data with subsequent dissemination of results, which aid clinical decision-making. Objective To evaluate, classify and analyze the diagnostic performance, strengths and limitations of existing acute care ESS systems. Data Sources All available to us studies in Ovid MEDLINE, Ovid EMBASE, CINAHL and Scopus databases, from as early as January 1972 through the first week of September 2012. Study Selection: Prospective and retrospective trials, examining the diagnostic performance of inpatient ESS and providing objective diagnostic data including sensitivity, specificity, positive and negative predictive values. Data Extraction Two independent reviewers extracted diagnostic performance data on ESS systems, including clinical area, number of decision points, sensitivity and specificity. Positive and negative likelihood ratios were calculated for each healthcare ESS system. A likelihood matrix summarizing the various ESS systems performance was created. Results The described search strategy yielded 1639 articles. Of these, 1497 were excluded on abstract information. After full text review, abstraction and arbitration with a third reviewer, 33 studies met inclusion criteria, reporting 102,611 ESS decision points. The yielded I2 was high (98.8%), precluding meta-analysis. Performance was variable, with sensitivities ranging from 21% –100% and specificities ranging from 5%-100%. Conclusions There is significant heterogeneity in the diagnostic performance of the available ESS implements in acute care, stemming from the wide spectrum of different clinical entities and ESS systems. Based on the results, we introduce a conceptual framework using a likelihood ratio matrix for evaluation and meaningful application of future, frontline clinical decision support systems. PMID:23874359

The ritual abuse of children: clinical features and diagnostic reasoning.

PubMed

Nurcombe, B; Unützer, J

1991-03-01

A case of alleged ritual sexual abuse is presented. Clinical recognition and diagnostic reasoning are discussed. After a brief account of modern satanism, it is concluded that, although the evidence for the occurrence of ritual abuse is sketchy, a high index of suspicion is appropriate.

76 FR 33303 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

... comments should be received within 60 days of this notice. Proposed Project Survey of Rapid Influenza... Description The Survey of Rapid Influenza Diagnostic Testing Practices in Clinical Laboratories is a national systematic study investigating rapid influenza diagnostic testing practices in clinical [[Page 33304...

ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation

ERIC Educational Resources Information Center

Pappas, Danielle

2006-01-01

This article reviews the "ADHD Rating Scale-IV: Checklist, norms, and clinical interpretation," is a norm-referenced checklist that measures the symptoms of attention deficit/hyperactivity disorder (ADHD) according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric…

When BVD doesn't look like BVD

USDA-ARS?s Scientific Manuscript database

Due to the sheer number of different clinical presentations existing under the BVD umbrella, diagnosing BVD based on clinical signs is not advisable. Thus diagnosis relies upon testing of samples in diagnostic laboratories. In the US, most of the diagnostic effort has been focused on identifying a...

Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

PubMed

Petersen, Tom; Laslett, Mark; Juhl, Carsten

2017-05-12

Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Diagnostic potential of optical coherence tomography in non-melanoma skin cancer: a clinical study

NASA Astrophysics Data System (ADS)

Mogensen, Mette; Thrane, Lars; Jørgensen, Thomas Martini; Jemec, Gregor B. E.

2007-07-01

Introduction: Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the Western World. OCT has proved potential in assisting clinical diagnosis and perhaps reducing the need for biopsies in NMSC. As non-invasive treatment is increasingly used for NMSC patients with superficial lesions, the development of non-invasive diagnostic technologies is highly relevant. Methods: The aim of this cross-sectional clinical study, enrolling 100 NMSC patients and 20 healthy volunteers, is to investigate the diagnostic accuracy and applicability of OCT in NMSC diagnosis. Our OCT-system has been developed at Risoe National Laboratory, Denmark and offers ppolarization sensitive-OCT (PS-OCT) that may have additional advantaged as NMSC differ in content of birefringent collagens from normal skin. Results: Basal cell carcinomas (BCC) can in some cases be distinguished from normal skin in OCT-images, as normal skin exhibits a layered structure this layering is not present in BCC and sometimes not in actinic keratosis (AK). BCC lesions seem to be clearly less reflective than normal tissue. The predictive value of OCT in NMSC will be presented from a clinical point of view. Discussion: The earlier a skin cancer is diagnosed, the better the prognosis. Estimation of diagnostic accuracy and abilities of OCT in clinical studies of skin cancer patients is essential to establish the role and future set-ups for diagnostic OCT-systems.

Study protocol of the internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE), Korea, 2015–2019

PubMed Central

Jeong, Hyunsuk; Jo, Sun-Jin; Lee, Seung-Yup; Kim, Eunjin; Son, Hye Jung; Han, Hyun-ho; Lee, Hae Kook; Kweon, Yong-Sil; Bhang, Soo-young; Choi, Jung-Seok; Kim, Bung-Nyun; Gentile, Douglas A; Potenza, Marc N

2017-01-01

Introduction In 2013, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine internet gaming disorder (IGD) diagnostic criteria as a condition warranting further empirical and clinical research. The aim of this study is to clarify the natural and clinical courses of IGD proposed DSM-5 in adolescents and to evaluate its risk and protective factors. Methods and analysis The Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence (iCURE) study is an ongoing multidisciplinary, prospective, longitudinal cohort study conducted in 21 schools in Korea. Participant recruitment commenced in March 2015 with the goal of registering 3000 adolescents. The baseline assessment included surveys on emotional, social and environmental characteristics. A parent or guardian completed questionnaires and a structured psychiatric comorbidity diagnostic interview regarding their children. Adolescents with the Internet Game Use-Elicited Symptom Screen total scores of 6 or higher were asked to participate in the clinical diagnostic interview. Two subcohorts of adolescents were constructed: a representative subcohort and a clinical evaluation subcohort. The representative subcohort comprises a randomly selected 10% of the iCURE to investigate the clinical course of IGD based on clinical diagnosis and to estimate the false negative rate. The clinical evaluation subcohort comprised participants meeting three or more of the nine IGD criteria, determined by clinical diagnostic interview, to show the clinical course of IGD. Follow-up data will be collected annually for the 3 years following the baseline assessments. The primary endpoint is 2-year incidence, remission and recurrence rates of IGD. Cross-sectional and longitudinal associations between exposures and outcomes as well as mediation factors will be evaluated. Ethics and dissemination This study is approved by the Institutional Review Board of the Catholic University of Korea. Results will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (identifier: NCT02415322). PMID:28982839

Indication for peritoneal biopsy in tuberculous peritonitis.

PubMed

Chow, Kai Ming; Chow, Viola Chi-Ying; Szeto, Cheuk Chun

2003-06-01

With the introduction of effective antituberculous chemotherapy, the clinical outcome of tuberculous peritonitis depends much on the diagnostic accuracy of this disease entity. This review summarizes the current state-of-the-art thinking regarding the protean manifestation and diagnostic modalities of this major infectious disease. This review was compiled after an extensive search of the current and historical literature, comprising 1,070 cases of tuberculous peritonitis. A number of important areas were highlighted, with emphasis on the diagnostic value and clinical impact of peritoneal biopsy. We believe an aggressive diagnostic approach, particularly with peritoneal biopsy, is warranted for the diagnosis and timely treatment of tuberculous peritonitis.

A diagnostic approach to hemochromatosis

PubMed Central

Tavill, Anthony S; Adams, Paul C

2006-01-01

In the present clinical review, a diagnostic approach to hemochromatosis is discussed from the perspective of two clinicians with extensive experience in this area. The introduction of genetic testing and large-scale population screening studies have broadened our understanding of the clinical expression of disease and the utility of biochemical iron tests for the detection of disease and for the assessment of disease severity. Liver biopsy has become more of a prognostic test than a diagnostic test. The authors offer a stepwise, diagnostic algorithm based on current evidence-based data, that they regard as most cost-effective. An early diagnosis can lead to phlebotomy therapy to prevent the development of cirrhosis. PMID:16955151

Teaching clinical reasoning: case-based and coached.

PubMed

Kassirer, Jerome P

2010-07-01

Optimal medical care is critically dependent on clinicians' skills to make the right diagnosis and to recommend the most appropriate therapy, and acquiring such reasoning skills is a key requirement at every level of medical education. Teaching clinical reasoning is grounded in several fundamental principles of educational theory. Adult learning theory posits that learning is best accomplished by repeated, deliberate exposure to real cases, that case examples should be selected for their reflection of multiple aspects of clinical reasoning, and that the participation of a coach augments the value of an educational experience. The theory proposes that memory of clinical medicine and clinical reasoning strategies is enhanced when errors in information, judgment, and reasoning are immediately pointed out and discussed. Rather than using cases artificially constructed from memory, real cases are greatly preferred because they often reflect the false leads, the polymorphisms of actual clinical material, and the misleading test results encountered in everyday practice. These concepts foster the teaching and learning of the diagnostic process, the complex trade-offs between the benefits and risks of diagnostic tests and treatments, and cognitive errors in clinical reasoning. The teaching of clinical reasoning need not and should not be delayed until students gain a full understanding of anatomy and pathophysiology. Concepts such as hypothesis generation, pattern recognition, context formulation, diagnostic test interpretation, differential diagnosis, and diagnostic verification provide both the language and the methods of clinical problem solving. Expertise is attainable even though the precise mechanisms of achieving it are not known.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PubMed

Shirahata, Mitsuaki; Iwao-Koizumi, Kyoko; Saito, Sakae; Ueno, Noriko; Oda, Masashi; Hashimoto, Nobuo; Takahashi, Jun A; Kato, Kikuya

2007-12-15

Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

Challenges in pediatric chronic inflammatory demyelinating polyneuropathy.

PubMed

Haliloğlu, Göknur; Yüksel, Deniz; Temoçin, Cağri Mesut; Topaloğlu, Haluk

2016-12-01

Chronic inflammatory demyelinating neuropathy, a treatable immune-mediated disease of the peripheral nervous system is less common in childhood compared to adults. Despite different sets of diagnostic criteria, lack of a reliable biologic marker leads to challenges in diagnosis, follow-up and treatment. Our first aim was to review clinical presentation, course, response to treatment, and prognosis in our childhood patients. We also aimed to document diagnostic and therapeutic pitfalls and challenges at the bedside. Our original cohort consisted of 23 pediatric patients who were referred to us with a clinical diagnosis of chronic inflammatory demyelinating neuropathy. Seven patients reaching to an alternative diagnosis were excluded. In the remaining patients, diagnostic, treatment and follow-up data were compared in typical patients who satisfied both clinical and electrodiagnostic criteria and atypical patients who failed to meet minimal research chronic inflammatory demyelinating neuropathy electrodiagnostic requirements. Eight of 16 patients (50%) met the minimal chronic inflammatory demyelinating neuropathy research diagnostic requirements. There was only a statistically significant difference (p = 0.010) in terms of European Neuromuscular Centre childhood chronic inflammatory diagnostic mandatory clinical criteria between the two groups. Misdiagnosis due to errors in electrophysiological interpretation (100%, n = 8), cerebrospinal fluid cytoalbuminologic dissociation (100%, n = 4 and/or subjective improvement on any immunotherapy modality (80 ± 19.27%)) was frequent. Pediatric CIDP is challenging in terms of diagnostic and therapeutic pitfalls at the bedside. Diagnostic errors due to electrophysiological interpretation, cerebrospinal fluid cytoalbuminologic dissociation, and/or subjective improvement on immunotherapy should be considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Model of critical diagnostic reasoning: achieving expert clinician performance.

PubMed

Harjai, Prashant Kumar; Tiwari, Ruby

2009-01-01

Diagnostic reasoning refers to the analytical processes used to determine patient health problems. While the education curriculum and health care system focus on training nurse clinicians to accurately recognize and rescue clinical situations, assessments of non-expert nurses have yielded less than satisfactory data on diagnostic competency. The contrast between the expert and non-expert nurse clinician raises the important question of how differences in thinking may contribute to a large divergence in accurate diagnostic reasoning. This article recognizes superior organization of one's knowledge base, using prototypes, and quick retrieval of pertinent information, using similarity recognition as two reasons for the expert's superior diagnostic performance. A model of critical diagnostic reasoning, using prototypes and similarity recognition, is proposed and elucidated using case studies. This model serves as a starting point toward bridging the gap between clinical data and accurate problem identification, verification, and management while providing a structure for a knowledge exchange between expert and non-expert clinicians.

DSM-V from the perspective of the DSM-IV experience.

PubMed

Walsh, B Timothy

2007-11-01

This article provides a brief overview of the development of the diagnostic criteria for eating disorders in DSM-IV. The process by which DSM-IV was developed is reviewed, including perspectives on what constitutes diagnostic validity and clinical utility, and their importance in assessing proposed changes in diagnostic criteria. The question of whether alterations in diagnostic criteria would clearly improve clinical utility was a major consideration in the DSM-IV process. Because of concerns that changes in diagnostic criteria would be disruptive and might entail loss of established knowledge, the DSM-IV Task Force assumed a generally conservative stance vis-à-vis change. The process of developing DSM-V is just beginning, and it is far from clear what alterations in diagnostic criteria for eating disorders will occur. However, the evolution of DSM-IV may provide a useful perspective on the development of DSM-V. (c) 2007 by Wiley Periodicals, Inc.

Ultrasound-Guided Percutaneous Thyroid Nodule Core Biopsy: Clinical Utility in Patients with Prior Nondiagnostic Fine-Needle Aspirate

PubMed Central

Vij, Abhinav; Seale, Melanie K.; Desai, Gaurav; Halpern, Elkan; Faquin, William C.; Parangi, Sareh; Hahn, Peter F.; Daniels, Gilbert H.

2012-01-01

Background Five percent to 20% of thyroid nodule fine-needle aspiration (FNA) samples are nondiagnostic. The objective of this study was to determine whether a combination of FNA and core biopsy (CFNACB) would yield a higher proportion of diagnostic readings compared with FNA alone in patients with a history of one or more prior nondiagnostic FNA readings. Methods We conducted a retrospective study of 90 core biopsies (CBs) performed in 82 subjects (55 women and 27 men) between 2006 and 2008 in an outpatient clinic. Results CFNACB yielded a diagnostic reading in 87%. The diagnostic reading yield of the CB component of CFNACB was significantly superior to the concurrent FNA component, with CB yielding a diagnosis in 77% of cases and FNA yielding a diagnosis in 47% (p<0.0001). The combination of CB and FNA had a higher diagnostic reading yield than either alone. In 69 nodules that had only one prior nondiagnostic FNA, CB was diagnostic in 74%, FNA was diagnostic in 52%, CFNACB was diagnostic in 87%, and CB performed significantly better than FNA (p=0.0135). In 21 nodules with two or more prior nondiagnostic FNAs, CFNACB and CB were diagnostic in 86%, FNA was diagnostic in 29%, and CB was significantly better than FNA (p=0.0005). Clinical, ultrasound, or histopathologic follow-up was available for 81% (73/90) of the CFNACB procedures. No subject with a benign CFNACB reading was diagnosed with thyroid malignancy in the follow-up period (range 4–37 months, mean 18 months), although one subject had minimal increase in nodule size and was awaiting repeat sonography at study conclusion. Conclusion Thyroid nodule CFNACB is safe and clinically useful in selected patients when a prior FNA reading is nondiagnostic. CFNACB is superior to either CB or FNA alone. CFNACB should be strongly considered as an alternative to surgery in individuals with two prior nondiagnostic FNAs. PMID:22304390

Diagnostic Criteria, Classification and Treatment Goals in Multiple Sclerosis: The Chronicles of Time and Space.

PubMed

Ntranos, Achilles; Lublin, Fred

2016-10-01

Multiple sclerosis (MS) is one of the most diverse human diseases. Since its first description by Charcot in the nineteenth century, the diagnostic criteria, clinical course classification, and treatment goals for MS have been constantly revised and updated to improve diagnostic accuracy, physician communication, and clinical trial design. These changes have improved the clinical outcomes and quality of life for patients with the disease. Recent technological and research breakthroughs will almost certainly further change how we diagnose, classify, and treat MS in the future. In this review, we summarize the key events in the history of MS, explain the reasoning behind the current criteria for MS diagnosis, classification, and treatment, and provide suggestions for further improvements that will keep enhancing the clinical practice of MS.

Advances in diagnostic and treatment modalities for intracranial tumors.

PubMed

Dickinson, P J

2014-01-01

Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

[Diagnostic imaging and acute abdominal pain].

PubMed

Liljekvist, Mads Svane; Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

2015-01-19

Acute abdominal pain is a common clinical condition. Clinical signs and symptoms can be difficult to interpret, and diagnostic imaging may help to identify intra-abdominal disease. Conventional X-ray, ultrasound (US) and computed tomography (CT) of the abdomen vary in usability between common surgical causes of acute abdominal pain. Overall, conventional X-ray cannot confidently diagnose or rule out disease. US and CT are equally trustworthy for most diseases. US with subsequent CT may enhance diagnostic precision. Magnetic resonance seems promising for future use in acute abdominal imaging.

Evidence-Based Diagnosis: Incorporating Diagnostic Instruments into Clinical Practice

ERIC Educational Resources Information Center

Doss, Amanda Jensen

2005-01-01

This article is intended to serve as a practical guide for practitioners interested in incorporating evidence-based diagnosis (EBD) instruments into their clinical practices to refine the diagnostic process. Three measures are used to illustrate this process, the DISC-IV (Shaffer et al., 2000), the Schedule for Affective Disorders and…

The Validity of Projective Techniques and Their Clinical and Research Contributions

ERIC Educational Resources Information Center

Blatt, Sidney J.

1975-01-01

Questions about the limitations and potential contributions of projective techniques in research are considered and issues which limit the contributions of diagnostic assessment and projective techniques in clinical practice are examined. A proposal is made for conceptualizing diagnostic assessment as a more integral part of the therapeutic…

Outbreak!: Teaching Clinical and Diagnostic Microbiology Methodologies with an Interactive Online Game

ERIC Educational Resources Information Center

Clark, Sherri; Smith, Geoffrey Battle

2004-01-01

Outbreak! is an online, interactive educational game that helps students and teachers learn and evaluate clinical microbiology skills. When the game was used in introductory microbiology laboratories, qualitative evaluation by students showed very positive responses and increased learning. Outbreak! allows students to design diagnostic tests and…

Clinical Validation of the "Sedentary Lifestyle" Nursing Diagnosis in Secondary School Students

ERIC Educational Resources Information Center

de Oliveira, Marcos Renato; da Silva, Viviane Martins; Guedes, Nirla Gomes; de Oliveira Lopes, Marcos Venícios

2016-01-01

This study clinically validated the nursing diagnosis of "sedentary lifestyle" (SL) among 564 Brazilian adolescents. Measures of diagnostic accuracy were calculated for defining characteristics, and Mantel--Haenszel analysis was used to identify related factors. The measures of diagnostic accuracy showed that the following defining…

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.

PubMed

Deans, Zandra C; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjö, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn Jl; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A

2017-01-01

The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.

Clinical recommendations of cardiac magnetic resonance, Part I: ischemic and valvular heart disease: a position paper of the working group 'Applicazioni della Risonanza Magnetica' of the Italian Society of Cardiology.

PubMed

Aquaro, Giovanni Donato; Di Bella, Gianluca; Castelletti, Silvia; Maestrini, Viviana; Festa, Pierluigi; Ait-Ali, Lamia; Masci, Pier Giorgio; Monti, Lorenzo; di Giovine, Gabriella; De Lazzari, Manuel; Cipriani, Alberto; Guaricci, Andrea I; Dellegrottaglie, Santo; Pepe, Alessia; Marra, Martina Perazzolo; Pontone, Gianluca

2017-04-01

Cardiac magnetic resonance (CMR) has emerged as a reliable and accurate diagnostic tool for the evaluation of patients with cardiac disease in several clinical settings and with proven additional diagnostic and prognostic value compared with other imaging modalities. This document has been developed by the working group on the 'application of CMR' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical applications of CMR and to inform cardiologists on how to implement their clinical and diagnostic pathways with the inclusion of this technique in clinical practice. The writing committee consisted of members of the working group of the Italian Society of Cardiology and two external peer reviewers with acknowledged experience in the field of CMR.

Understanding the properties of diagnostic tests - Part 2: Likelihood ratios.

PubMed

Ranganathan, Priya; Aggarwal, Rakesh

2018-01-01

Diagnostic tests are used to identify subjects with and without disease. In a previous article in this series, we examined some attributes of diagnostic tests - sensitivity, specificity, and predictive values. In this second article, we look at likelihood ratios, which are useful for the interpretation of diagnostic test results in everyday clinical practice.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

Palmar hyperhidrosis: clinical, pathophysiological, diagnostic and therapeutic aspects.

PubMed

Romero, Flávio Ramalho; Haddad, Gabriela Roncada; Miot, Hélio Amante; Cataneo, Daniele Cristina

2016-01-01

Palmar hyperhidrosis affects up to 3% of the population and inflict significant impact on quality of life. It is characterized by chronic excessive sweating, not related to the necessity of heat loss. It evolves from a localized hyperactivity of the sympathetic autonomic system and can be triggered by stressful events. In this study, the authors discuss clinical findings, pathophysiological, diagnostic and therapeutic issues (clinical and surgical) related to palmar hyperhidrosis.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Evaluating a Dental Diagnostic Terminology in an Electronic Health Record

PubMed Central

White, Joel M.; Kalenderian, Elsbeth; Stark, Paul C.; Ramoni, Rachel L.; Vaderhobli, Ram; Walji, Muhammad F.

2011-01-01

Standardized treatment procedure codes and terms are routinely used in dentistry. Utilization of a diagnostic terminology is common in medicine, but there is not a satisfactory or commonly standardized dental diagnostic terminology available at this time. Recent advances in dental informatics have provided an opportunity for inclusion of diagnostic codes and terms as part of treatment planning and documentation in the patient treatment history. This article reports the results of the use of a diagnostic coding system in a large dental school’s predoctoral clinical practice. A list of diagnostic codes and terms, called Z codes, was developed by dental faculty members. The diagnostic codes and terms were implemented into an electronic health record (EHR) for use in a predoctoral dental clinic. The utilization of diagnostic terms was quantified. The validity of Z code entry was evaluated by comparing the diagnostic term entered to the procedure performed, where valid diagnosis-procedure associations were determined by consensus among three calibrated academically based dentists. A total of 115,004 dental procedures were entered into the EHR during the year sampled. Of those, 43,053 were excluded from this analysis because they represent diagnosis or other procedures unrelated to treatments. Among the 71,951 treatment procedures, 27,973 had diagnoses assigned to them with an overall utilization of 38.9 percent. Of the 147 available Z codes, ninety-three were used (63.3 percent). There were 335 unique procedures provided and 2,127 procedure/diagnosis pairs captured in the EHR. Overall, 76.7 percent of the diagnoses entered were valid. We conclude that dental diagnostic terminology can be incorporated within an electronic health record and utilized in an academic clinical environment. Challenges remain in the development of terms and implementation and ease of use that, if resolved, would improve the utilization. PMID:21546594

Is there any evidence for the validity of diagnostic criteria used for accommodative and nonstrabismic binocular dysfunctions?

PubMed Central

Cacho-Martínez, Pilar; García-Muñoz, Ángel; Ruiz-Cantero, María Teresa

2013-01-01

Purpose To analyze the diagnostic criteria used in the scientific literature published in the past 25 years for accommodative and nonstrabismic binocular dysfunctions and to explore if the epidemiological analysis of diagnostic validity has been used to propose which clinical criteria should be used for diagnostic purposes. Methods We carried out a systematic review of papers on accommodative and non-strabic binocular disorders published from 1986 to 2012 analysing the MEDLINE, CINAHL, PsycINFO and FRANCIS databases. We admitted original articles about diagnosis of these anomalies in any population. We identified 839 articles and 12 studies were included. The quality of included articles was assessed using the QUADAS-2 tool. Results The review shows a wide range of clinical signs and cut-off points between authors. Only 3 studies (regarding accommodative anomalies) assessed diagnostic accuracy of clinical signs. Their results suggest using the accommodative amplitude and monocular accommodative facility for diagnosing accommodative insufficiency and a high positive relative accommodation for accommodative excess. The remaining 9 articles did not analyze diagnostic accuracy, assessing a diagnosis with the criteria the authors considered. We also found differences between studies in the way of considering patients’ symptomatology. 3 studies of 12 analyzed, performed a validation of a symptom survey used for convergence insufficiency. Conclusions Scientific literature reveals differences between authors according to diagnostic criteria for accommodative and nonstrabismic binocular dysfunctions. Diagnostic accuracy studies show that there is only certain evidence for accommodative conditions. For binocular anomalies there is only evidence about a validated questionnaire for convergence insufficiency with no data of diagnostic accuracy. PMID:24646897

Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies

PubMed Central

Fabregas, N.; Ewig, S.; Torres, A.; El-Ebiary, M.; Ramirez, J.; de la Bellacasa, J. P.; Bauer, T.; Cabello, H.

1999-01-01

BACKGROUND—A study was undertaken to assess the diagnostic value of different clinical criteria and the impact of microbiological testing on the accuracy of clinical diagnosis of suspected ventilator associated pneumonia (VAP).
METHODS—Twenty five deceased mechanically ventilated patients were studied prospectively. Immediately after death, multiple bilateral lung biopsy specimens (16 specimens/patient) were obtained for histological examination and quantitative lung cultures. The presence of both histological pneumonia and positive lung cultures was used as a reference test.
RESULTS—The presence of infiltrates on the chest radiograph and two of three clinical criteria (leucocytosis, purulent secretions, fever) had a sensitivity of 69% and a specificity of 75%; the corresponding numbers for the clinical pulmonary infection score (CPIS) were 77% and 42%. Non-invasive as well as invasive sampling techniques had comparable values. The combination of all techniques achieved a sensitivity of 85% and a specificity of 50%, and these values remained virtually unchanged despite the presence of previous treatment with antibiotics. When microbiological results were added to clinical criteria, adequate diagnoses originating from microbiological results which might have corrected false positive and false negative clinical judgements (n = 5) were countered by a similar proportion of inadequate diagnoses (n =6).
CONCLUSIONS—Clinical criteria had reasonable diagnostic values. CPIS was not superior to conventional clinical criteria. Non-invasive and invasive sampling techniques had diagnostic values comparable to clinical criteria. An algorithm guiding antibiotic treatment exclusively by microbiological results does not increase the overall diagnostic accuracy and carries the risk of undertreatment.

 PMID:10491448

Diagnostic Labels, Stigma, and Participation in Research Related to Dementia and Mild Cognitive Impairment

PubMed Central

Garand, Linda; Lingler, Jennifer H.; Conner, Kyaien O.; Dew, Mary Amanda

2010-01-01

Health care professionals use diagnostic labels to classify individuals for both treatment and research purposes. Despite their clear benefits, diagnostic labels also serve as cues that activate stigma and stereotypes. Stigma associated with the diagnostic labels of dementia and mild cognitive impairment (MCI) can have a significant and negative impact on interpersonal relationships, interactions with the health care community, attitudes about service utilization, and participation in clinical research. The impact of stigma also extends to the family caregivers of individuals bearing such labels. In this article, we use examples from our investigations of individuals with dementia or MCI and their family caregivers to examine the impact of labeling and stigma on clinical research participation. We also discuss how stigma can affect numerous aspects of the nursing research process. Strategies are presented for addressing stigma-related barriers to participation in clinical research on dementia and MCI. PMID:20077972

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

PubMed

Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

Pharmacogenetics in Europe: barriers and opportunities.

PubMed

Gurwitz, D; Zika, E; Hopkins, M M; Gaisser, S; Ibarreta, D

2009-01-01

This paper reviews the current situation in the field of pharmacogenetics/pharmacogenomics (PGx) in Europe. High expectations surrounding the clinical application of PGx remain largely unmet, as only a limited number of such applications have actually reached the market and clinical practice. Thus, the potential impact of PGx-based diagnostics on healthcare and its socio-economic implications are still unclear. With the aim of shedding some light on these uncertainties, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre (JRC) has conducted a review of the 'state of the art' and a further analysis on the use of pharmacogenetics diagnostics for preventing toxic drug reactions and improving drug efficacy in Europe. The paper presents highlights from the JRC-IPTS studies and discusses possibilities for improving translation of PGx research in Europe by comparing some experiences in the USA. We also illustrate the related barriers for the clinical uptake of PGx in Europe with specific case-studies. Most of the barriers identified extend beyond the European context. This reflects the global problems of scarcity of data demonstrating proven clinical validity or utility and favorable cost-effectiveness studies to support the clinical application of PGx diagnostic tests in the clinical setting. Another key barrier is the lack of incentives for the private sector to invest in the development and licensing of PGx diagnostic tests for improving the safety and efficacy of out-of-patent drugs. It therefore seems that one key aspect where policy can affect the clinical uptake of PGx is via sustaining large-scale industry-academia collaborations for developing and proving the utility of PGx diagnostics. Copyright 2009 S. Karger AG, Basel.

Clinical Dental Faculty Members' Perceptions of Diagnostic Errors and How to Avoid Them.

PubMed

Nikdel, Cathy; Nikdel, Kian; Ibarra-Noriega, Ana; Kalenderian, Elsbeth; Walji, Muhammad F

2018-04-01

Diagnostic errors are increasingly recognized as a source of preventable harm in medicine, yet little is known about their occurrence in dentistry. The aim of this study was to gain a deeper understanding of clinical dental faculty members' perceptions of diagnostic errors, types of errors that may occur, and possible contributing factors. The authors conducted semi-structured interviews with ten domain experts at one U.S. dental school in May-August 2016 about their perceptions of diagnostic errors and their causes. The interviews were analyzed using an inductive process to identify themes and key findings. The results showed that the participants varied in their definitions of diagnostic errors. While all identified missed diagnosis and wrong diagnosis, only four participants perceived that a delay in diagnosis was a diagnostic error. Some participants perceived that an error occurs only when the choice of treatment leads to harm. Contributing factors associated with diagnostic errors included the knowledge and skills of the dentist, not taking adequate time, lack of communication among colleagues, and cognitive biases such as premature closure based on previous experience. Strategies suggested by the participants to prevent these errors were taking adequate time when investigating a case, forming study groups, increasing communication, and putting more emphasis on differential diagnosis. These interviews revealed differing perceptions of dental diagnostic errors among clinical dental faculty members. To address the variations, the authors recommend adopting shared language developed by the medical profession to increase understanding.

27 The DiPEP (Diagnosis of PE in Pregnancy) study: can clinical assessment, d-dimer or chest x-ray be used to select pregnant or postpartum women with suspected PE for diagnostic imaging?

PubMed

Goodacre, Steve; Horspool, Kimberley; Nelson-Piercy, Catherine; Knight, Marian; Shephard, Neil; Lecky, Fiona; Thomas, Steven; Hunt, Beverley; Fuller, Gordon

2017-12-01

To determine whether clinical features (in the form of a clinical decision rule) or d-dimer can be used to select pregnant or postpartum women with suspected PE for diagnostic imaging. Observational cohort study augmented with additional cases. Consultant-led maternity units participating in the UK Obstetric Surveillance System (UKOSS) and emergency departments and maternity units at eleven prospectively recruiting sites. 198 pregnant or postpartum women with diagnosed PE identified through UKOSS and 324 pregnant or postpartum women with suspected PE from prospectively recruiting sites. Data were collected relating to clinical features, elements of clinical decision rules, d-dimer measurements, diagnostic imaging, treatment for PE and adverse outcomes. Women were classified as having or not having PE on the basis of diagnostic imaging, treatment and subsequent adverse outcomes. Primary analysis was limited to women with conclusive diagnostic imaging. Secondary analyses included women with clinically diagnosed or ruled out PE. The primary analysis included 181 women with PE and 259 without. Most clinical features showed no association with PE. The only exceptions were number of previous pregnancies over 24 weeks (p=0.017), no varicose veins (p=0.045), no recent long haul travel (p=0.006), recent surgery including caesarean section (p=0.001), increased temperature (p=0.003), low oxygen saturation (p<0.001), PE-related chest x-ray abnormality (p=0.01) and other chest x-ray abnormality (p=0.001).Clinical decision rules had areas under the receiver-operator characteristic curve ranging from 0.577 to 0.732. No clinically useful threshold for decision-making was identified for any rule. The sensitivities and specificities of d-dimer were 88.4% and 8.8% using the standard laboratory threshold and 69.8% and 32.8% using a pregnancy-specific threshold. Clinical decision rules, d-dimer and chest x-ray should not be used to select pregnant or postpartum women with suspected PE for diagnostic imaging. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Review of 20 Years of Research on Overdiagnosis and Underdiagnosis in the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project

PubMed Central

2016-01-01

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project represents an integration of research methodology into a community-based outpatient practice affiliated with an academic medical centre. The MIDAS project is the largest clinical epidemiological study using semi-structured interviews to assess a wide range of psychiatric disorders in a general clinical outpatient practice. In an early report from the MIDAS project, we found that across diagnostic categories clinicians using unstandardized, unstructured clinical interviews underrecognized diagnostic comorbidity, compared with the results of semi-structured interviews. Moreover, we found that the patients often wanted treatment for symptoms of disorders that were diagnosed as comorbid, rather than principal, conditions. This highlighted the importance, from the patient’s perspective, of conducting thorough diagnostic interviews to diagnose disorders that are not related to the patient’s chief complaint because patients often desire treatment for these additional diagnoses. While several of the initial papers from the MIDAS project identified problems with the detection of comorbid disorders in clinical practice, regarding the diagnosis of bipolar disorder we observed the emergence of an opposite phenomenon—clinician overdiagnosis. The results from the MIDAS project, along with other studies of diagnosis in routine clinical practice, have brought to the forefront the problem with diagnosis in routine clinical practice. An important question is what do these findings suggest about the community standard of care in making psychiatric diagnoses, and whether and how the standard of care should be changed? The implications are discussed. PMID:27253697

A Review of 20 Years of Research on Overdiagnosis and Underdiagnosis in the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project.

PubMed

Zimmerman, Mark

2016-02-01

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project represents an integration of research methodology into a community-based outpatient practice affiliated with an academic medical centre. The MIDAS project is the largest clinical epidemiological study using semi-structured interviews to assess a wide range of psychiatric disorders in a general clinical outpatient practice. In an early report from the MIDAS project, we found that across diagnostic categories clinicians using unstandardized, unstructured clinical interviews underrecognized diagnostic comorbidity, compared with the results of semi-structured interviews. Moreover, we found that the patients often wanted treatment for symptoms of disorders that were diagnosed as comorbid, rather than principal, conditions. This highlighted the importance, from the patient's perspective, of conducting thorough diagnostic interviews to diagnose disorders that are not related to the patient's chief complaint because patients often desire treatment for these additional diagnoses. While several of the initial papers from the MIDAS project identified problems with the detection of comorbid disorders in clinical practice, regarding the diagnosis of bipolar disorder we observed the emergence of an opposite phenomenon-clinician overdiagnosis. The results from the MIDAS project, along with other studies of diagnosis in routine clinical practice, have brought to the forefront the problem with diagnosis in routine clinical practice. An important question is what do these findings suggest about the community standard of care in making psychiatric diagnoses, and whether and how the standard of care should be changed? The implications are discussed. © The Author(s) 2016.

Clinical decision-making: heuristics and cognitive biases for the ophthalmologist.

PubMed

Hussain, Ahsen; Oestreicher, James

Diagnostic errors have a significant impact on health care outcomes and patient care. The underlying causes and development of diagnostic error are complex with flaws in health care systems, as well as human error, playing a role. Cognitive biases and a failure of decision-making shortcuts (heuristics) are human factors that can compromise the diagnostic process. We describe these mechanisms, their role with the clinician, and provide clinical scenarios to highlight the various points at which biases may emerge. We discuss strategies to modify the development and influence of these processes and the vulnerability of heuristics to provide insight and improve clinical outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pregnancy and mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

PubMed

Radetskaya, L S; Makatsariya, A D; Bitsadze, V O; Khizroeva, J K

2018-07-01

The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.

Integrating Early Intervention for Borderline Personality Disorder and Mood Disorders.

PubMed

Chanen, Andrew M; Berk, Michael; Thompson, Katherine

2016-01-01

Borderline personality disorder (BPD) has been demonstrated to be a reliable and valid construct in young people (adolescents and young adults). Both borderline- and mood-related psychopathology become clinically apparent from puberty through to young adulthood, frequently co-occur, can reinforce one another, and can be difficult to differentiate clinically. This Gordian knot of overlapping clinical features, common risk factors, and precursors to both BPD and mood disorders complicates clinical assessment, prevention, and treatment. Regardless of whether an individual crosses an arbitrary diagnostic threshold, a considerable proportion of young people with borderline- and mood-related psychopathology will develop significant and persistent functional, vocational, and interpersonal impairment and disability during this critical risk and developmental period. There is a clear need for early intervention, but spurious diagnostic certainty risks stigma, misapplication of diagnostic labels, inappropriate treatment, and unfavorable outcomes. This article aims to integrate early intervention for BPD and mood disorders in the clinical context of developmental and phenomenological change and evolution. "Clinical staging," similar to disease staging in general medicine, is presented as a pragmatic, heuristic, and trans-diagnostic framework to guide prevention and intervention. It acknowledges that the early stages of these disorders cannot be disentangled sufficiently to allow for disorder-specific preventive measures and early interventions. Clinical staging defines an individual's location along the continuum of the evolving temporal course of a disorder. Such staging aids differentiation of early or milder clinical phenomena from those that accompany illness progression and chronicity, and suggests the application of appropriate and proportionate intervention strategies.

Clinical validation of the nursing diagnosis of dysfunctional family processes related to alcoholism.

PubMed

Mangueira, Suzana de Oliveira; Lopes, Marcos Venícios de Oliveira

2016-10-01

To evaluate the clinical validity indicators for the nursing diagnosis of dysfunctional family processes related to alcohol abuse. Alcoholism is a chronic disease that negatively affects family relationships. Studies on the nursing diagnosis of dysfunctional family processes are scarce in the literature. This diagnosis is currently composed of 115 defining characteristics, hindering their use in practice and highlighting the need for clinical validation. This was a diagnostic accuracy study. A sample of 110 alcoholics admitted to a reference centre for alcohol treatment was assessed during the second half of 2013 for the presence or absence of the defining characteristics of the diagnosis. Operational definitions were created for each defining characteristic based on concept analysis and experts evaluated the content of these definitions. Diagnostic accuracy measures were calculated from latent class models with random effects. All 89 clinical indicators were found in the sample and a set of 24 clinical indicators was identified as clinically valid for a diagnostic screening for family dysfunction from the report of alcoholics. Main clinical indicators with high specificity included sexual abuse, disturbance in academic performance in children and manipulation. The main indicators that showed high sensitivity values were distress, loss, anxiety, low self-esteem, confusion, embarrassment, insecurity, anger, loneliness, deterioration in family relationships and disturbance in family dynamics. Eighteen clinical indicators showed a high capacity for diagnostic screening for alcoholics (high sensitivity) and six indicators can be used for confirmatory diagnosis (high specificity). © 2016 John Wiley & Sons Ltd.

An automated diagnostic process (PDA) in clinical psychopharmacology. An exemplification of its use in a sulpiride versus haloperidol comparative trial.

PubMed

Castrogiovanni, P; Cassano, G B; Conti, L; Maggini, C; Bonollo, L; Sarteschi, P

1976-01-01

One of the main unsolved problems, and one which produces divergent results in clinical psychopharmacology, is that concerning the selection of patients and their diagnostic definition. An automated diagnostic procedure (PDA) was set up in order to classify each patient into one nosographic category on the basis of a cross-sectional examination of his mental state. Such diagnostic procedure appears particularly suitable for multicenter drug trials, since it gives a profile and a diagnostic definition of patients, assessed by investigators from different areas and with different cultural, and clinical backgrounds. In a multicenter trial (sulpiride versus haloperidol) PDA offered a chance to re-examine and analyze the characteristics of each patient and therefore to control the criteria followed for the sample selection in the various experimental settings. The agreement between clinician and computer diagnosis was 78.9%; this agreement rises to 85.5% if the computerlabelled schizo-affective syndromes are considered within the schizophrenic group. Moreover, and attempt has been made to relate psychopathological patterns to drug responses.

Reducing cognitive skill decay and diagnostic error: theory-based practices for continuing education in health care.

PubMed

Weaver, Sallie J; Newman-Toker, David E; Rosen, Michael A

2012-01-01

Missed, delayed, or wrong diagnoses can have a severe impact on patients, providers, and the entire health care system. One mechanism implicated in such diagnostic errors is the deterioration of cognitive diagnostic skills that are used rarely or not at all over a prolonged period of time. Existing evidence regarding maintenance of effective cognitive reasoning skills in the clinical education, organizational training, and human factors literatures suggest that continuing education plays a critical role in mitigating and managing diagnostic skill decay. Recent models also underscore the role of system level factors (eg, cognitive decision support tools, just-in-time training opportunities) in supporting clinical reasoning process. The purpose of this manuscript is to offer a multidisciplinary review of cognitive models of clinical decision making skills in order to provide a list of best practices for supporting continuous improvement and maintenance of cognitive diagnostic processes through continuing education. Copyright © 2012 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on CME, Association for Hospital Medical Education.

Assessing value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine.

PubMed

Akhmetov, Ildar; Bubnov, Rostyslav V

2015-01-01

Molecular diagnostic tests drive the scientific and technological uplift in the field of predictive, preventive, and personalized medicine offering invaluable clinical and socioeconomic benefits to the key stakeholders. Although the results of diagnostic tests are immensely influential, molecular diagnostic tests (MDx) are still grudgingly reimbursed by payers and amount for less than 5 % of the overall healthcare costs. This paper aims at defining the value of molecular diagnostic test and outlining the most important components of "value" from miscellaneous assessment frameworks, which go beyond accuracy and feasibility and impact the clinical adoption, informing healthcare resource allocation decisions. The authors suggest that the industry should facilitate discussions with various stakeholders throughout the entire assessment process in order to arrive at a consensus about the depth of evidence required for positive marketing authorization or reimbursement decisions. In light of the evolving "value-based healthcare" delivery practices, it is also recommended to account for social and ethical parameters of value, since these are anticipated to become as critical for reimbursement decisions and test acceptance as economic and clinical criteria.

Diagnostic communication in the memory clinic: a conversation analytic perspective

PubMed Central

Peel, Elizabeth

2015-01-01

Objectives: Whether and how patients should be told their dementia diagnosis, has been an area of much debate. While there is now recognition that early diagnosis is important for dementia care little research has looked at how dementia-related diagnostic information is actually verbally communicated. The limited previous research suggests that the absence of explicit terminology (e.g., use of the term Alzheimer's) is problematic. This paper interrogates this assumption through a conversation analysis of British naturalistic memory clinic interaction. Method: This paper is based on video-recordings of communication within a UK memory clinic. Appointments with 29 patients and accompanying persons were recorded, and the corpus was repeatedly listened to, in conjunction with the transcripts in order to identify the segments of talk where there was an action hearable as diagnostic delivery, that is where the clinician is evaluating the patient's condition. Results: Using a conversation analytic approach this analysis suggests that diagnostic communication, which is sensitive and responsive to the patient and their carers, is not predicated on the presence or absence of particular lexical choices. There is inherent complexity regarding dementia diagnosis, especially in the ‘early stages’, which is produced through and reflected in diagnostic talk in clinical encounters. Conclusion: In the context of continuity of dementia care, diagnostic information is communicated in a way that conforms to intersubjective norms of minimizing catastrophic reactions in medical communication, and is sensitive to problems associated with ‘insight’ in terms of delivery and receipt or non-receipt of diagnosis. PMID:25647148

Integration of Diagnostic Microbiology in a Model of Total Laboratory Automation.

PubMed

Da Rin, Giorgio; Zoppelletto, Maira; Lippi, Giuseppe

2016-02-01

Although automation has become widely utilized in certain areas of diagnostic testing, its adoption in diagnostic microbiology has proceeded much more slowly. To describe our real-world experience of integrating an automated instrument for diagnostic microbiology (Walk-Away Specimen Processor, WASPLab) within a model of total laboratory automation (TLA). The implementation process was divided into 2 phases. The former period, lasting approximately 6 weeks, entailed the installation of the WASPLab processor to operate as a stand-alone instrumentation, whereas the latter, lasting approximately 2 weeks, involved physical connection of the WASPLab with the automation. Using the WASPLab instrument in conjunction with the TLA model, we obtained a time savings equivalent to the work of 1.2 full-time laboratory technicians for diagnostic microbiology. The connection of WASPLab to TLA allowed its management by a generalist or clinical chemistry technician, with no need for microbiology skills on the part of either worker. Hence, diagnostic microbiology could be performed by the staff that is already using the TLA, extending their activities to include processing urgent clinical chemistry and hematology specimens. The time to result was also substantially improved. According to our experience, using the WASPLab instrument as part of a TLA in diagnostic microbiology holds great promise for optimizing laboratory workflow and improving the quality of testing. © American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability.

PubMed

Lee, Jin Sook; Hwang, Hee; Kim, Soo Yeon; Kim, Ki Joong; Choi, Jin Sun; Woo, Mi Jung; Choi, Young Min; Jun, Jong Kwan; Lim, Byung Chan; Chae, Jong Hee

2018-09-01

Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability. © The Korean Society for Laboratory Medicine.

Impact of Crop Management Diagnostic Clinics on Advisors' Recommendations and Producer Practices

ERIC Educational Resources Information Center

Wortmann, Charles S.; Glewen, Keith L.; Williams, Susan N.

2011-01-01

Adoption resulting from University of Nebraska-Lincoln Crop Management Diagnostic Clinic (CMDC) field days was evaluated using an on-line survey. Respondents reported significant gains in skills because of CMDC, but the gains were similar across skill areas. Adoption was affected by compatibility with the cropping system, relative advantage,…

Sharing the Diagnostic Process in the Clinical Teaching Environment: A Case Study

ERIC Educational Resources Information Center

Cuello-Garcia; Carlos

2005-01-01

Revealing or visualizing the thinking involved in making clinical decisions is a challenge. A case study is presented with a visual implement for sharing the diagnostic process. This technique adapts the Bayesian approach to the case presentation. Pretest probabilities and likelihood ratios are gathered to obtain post-test probabilities of every…

Clinical and diagnostic features of delayed hypoxic leukoencephalopathy.

PubMed

Shprecher, David R; Flanigan, Kevin M; Smith, A Gordon; Smith, Shawn M; Schenkenberg, Thomas; Steffens, John

2008-01-01

Delayed hypoxic leukoencephalopathy is an underrecognized syndrome of delayed demyelination, which is important to consider when delayed onset of neuropsychiatric symptoms follows a hypoxic event. The authors describe clinical and diagnostic features of three such cases, review the pathophysiology of delayed hypoxic leukoencephalopathy, and discuss features which may help distinguish it from toxic leukoencephalopathy.

Quantifying the added value of BNP in suspected heart failure in general practice: an individual patient data meta-analysis.

PubMed

Kelder, Johannes C; Cowie, Martin R; McDonagh, Theresa A; Hardman, Suzanna M C; Grobbee, Diederick E; Cost, Bernard; Hoes, Arno W

2011-06-01

Diagnosing early stages of heart failure with mild symptoms is difficult. B-type natriuretic peptide (BNP) has promising biochemical test characteristics, but its diagnostic yield on top of readily available diagnostic knowledge has not been sufficiently quantified in early stages of heart failure. To quantify the added diagnostic value of BNP for the diagnosis of heart failure in a population relevant to GPs and validate the findings in an independent primary care patient population. Individual patient data meta-analysis followed by external validation. The additional diagnostic yield of BNP above standard clinical information was compared with ECG and chest x-ray results. Derivation was performed on two existing datasets from Hillingdon (n=127) and Rotterdam (n=149) while the UK Natriuretic Peptide Study (n=306) served as validation dataset. Included were patients with suspected heart failure referred to a rapid-access diagnostic outpatient clinic. Case definition was according to the ESC guideline. Logistic regression was used to assess discrimination (with the c-statistic) and calibration. Of the 276 patients in the derivation set, 30.8% had heart failure. The clinical model (encompassing age, gender, known coronary artery disease, diabetes, orthopnoea, elevated jugular venous pressure, crackles, pitting oedema and S3 gallop) had a c-statistic of 0.79. Adding, respectively, chest x-ray results, ECG results or BNP to the clinical model increased the c-statistic to 0.84, 0.85 and 0.92. Neither ECG nor chest x-ray added significantly to the 'clinical plus BNP' model. All models had adequate calibration. The 'clinical plus BNP' diagnostic model performed well in an independent cohort with comparable inclusion criteria (c-statistic=0.91 and adequate calibration). Using separate cut-off values for 'ruling in' (typically implying referral for echocardiography) and for 'ruling out' heart failure--creating a grey zone--resulted in insufficient proportions of patients with a correct diagnosis. BNP has considerable diagnostic value in addition to signs and symptoms in patients suspected of heart failure in primary care. However, using BNP alone with the currently recommended cut-off levels is not sufficient to make a reliable diagnosis of heart failure.

A five-year experience with throat cultures.

PubMed

Shank, J C; Powell, T A

1984-06-01

This study addresses the usefulness of the throat culture in a family practice residency setting and explores the following questions: (1) Do faculty physicians clinically identify streptococcal pharyngitis better than residents? (2) With time, will residents and faculty physicians improve in their diagnostic accuracy? (3) Should the throat culture be used always, selectively, or never? A total of 3,982 throat cultures were obtained over a five-year study period with 16 percent positive for beta-hemolytic streptococci. The results were compared with the physician's clinical diagnosis of either "nonstreptococcal" (category A) or "streptococcal" (category B). Within category A, 363 of 3,023 patients had positive cultures (12 percent clinical diagnostic error rate). Within category B, 665 of 959 patients had negative cultures (69 percent clinical diagnostic error rate). Faculty were significantly better than residents in diagnosing streptococcal pharyngitis, but not in diagnosing nonstreptococcal sore throats. Neither faculty nor residents improved their diagnostic accuracy over time. Regarding age-specific recommendations, the findings support utilizing a throat culture in all children aged 2 to 15 years with sore throat, but in adults only when the physician suspects streptococcal pharyngitis.

Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis.

PubMed

Nolan, Danielle; Carlson, Martha

2016-06-01

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. © The Author(s) 2016.

Verification of performance specifications of a molecular test: cystic fibrosis carrier testing using the Luminex liquid bead array.

PubMed

Lacbawan, Felicitas L; Weck, Karen E; Kant, Jeffrey A; Feldman, Gerald L; Schrijver, Iris

2012-01-01

The number of clinical laboratories introducing various molecular tests to their existing test menu is continuously increasing. Prior to offering a US Food and Drug Administration-approved test, it is necessary that performance characteristics of the test, as claimed by the company, are verified before the assay is implemented in a clinical laboratory. To provide an example of the verification of a specific qualitative in vitro diagnostic test: cystic fibrosis carrier testing using the Luminex liquid bead array (Luminex Molecular Diagnostics, Inc, Toronto, Ontario). The approach used by an individual laboratory for verification of a US Food and Drug Administration-approved assay is described. Specific verification data are provided to highlight the stepwise verification approach undertaken by a clinical diagnostic laboratory. Protocols for verification of in vitro diagnostic assays may vary between laboratories. However, all laboratories must verify several specific performance specifications prior to implementation of such assays for clinical use. We provide an example of an approach used for verifying performance of an assay for cystic fibrosis carrier screening.

Clinical Issues in the Use of the "DSM-III-R" with African American Children: A Diagnostic Paradigm.

ERIC Educational Resources Information Center

Johnson, Ronn

1993-01-01

Reviews concerns related to diagnoses in delivery of mental health services, specifically, application of the principles of the Diagnostic and Statistical Manual of Mental Health Disorders (DSM-III-R) to African-American children. An alternative diagnostic model is proposed, and recommendations are made for enhancing the diagnostic process. (SLD)

Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

PubMed

Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p < 0.05, McNemar test). In the Pancreas-Outpatient-Clinic-Cohort, seven patients were diagnosed with AiP (n = 6 by U-AIP, n = 1 by Asian-criteria). International-Consensus-Diagnostic-Criteria confirmed the diagnosis in these individuals. Based on partial fulfillment of U-AIP, AiP was initially suspected in 13% (n = 10/77) of remaining patients from the Pancreas-Outpatient-Clinic-Cohort. In the Surgical-cohort, we identified one patient with AiP by U-AIP and ICDC. Unifying-Autoimmune-Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

[Conceptual foundation of the operational diagnostic approach in psychiatry].

PubMed

Jäger, M; Strauss, A; Frasch, K; Becker, T

2007-08-01

Based on the pioneering work of Emil Kraepelin, Karl Jaspers, Kurt Schneider and representatives of logical empiricism, the basic principles of the operational diagnostic approach in psychiatry are described. Operational diagnostic systems like ICD-10 and DSM-IV aimed at a standardisation of psychiatric language which can be accepted by different schools in psychiatry. However, ICD-10 and DSM-IV should not be misinterpreted as "nosology" because they do not reflect a specific model of psychiatric diseases. The advantages of operational diagnostic systems as instruments for communication in a clinical and scientific context are limited by the fact that they disregard the subjective psychopathology. This dimension, however, deserves attention in clinic and research.

Precision diagnostics: moving towards protein biomarker signatures of clinical utility in cancer.

PubMed

Borrebaeck, Carl A K

2017-03-01

Interest in precision diagnostics has been fuelled by the concept that early detection of cancer would benefit patients; that is, if detected early, more tumours should be resectable and treatment more efficacious. Serum contains massive amounts of potentially diagnostic information, and affinity proteomics has risen as an accurate approach to decipher this, to generate actionable information that should result in more precise and evidence-based options to manage cancer. To achieve this, we need to move from single to multiplex biomarkers, a so-called signature, that can provide significantly increased diagnostic accuracy. This Opinion article focuses on the progress being made in identifying protein biomarker signatures of clinical utility, using blood-based proteomics.

Palmar hyperhidrosis: clinical, pathophysiological, diagnostic and therapeutic aspects*

PubMed Central

Romero, Flávio Ramalho; Haddad, Gabriela Roncada; Miot, Hélio Amante; Cataneo, Daniele Cristina

2016-01-01

Abstract Palmar hyperhidrosis affects up to 3% of the population and inflict significant impact on quality of life. It is characterized by chronic excessive sweating, not related to the necessity of heat loss. It evolves from a localized hyperactivity of the sympathetic autonomic system and can be triggered by stressful events. In this study, the authors discuss clinical findings, pathophysiological, diagnostic and therapeutic issues (clinical and surgical) related to palmar hyperhidrosis. PMID:28099590

Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience.

PubMed

Lazaridis, Konstantinos N; Schahl, Kimberly A; Cousin, Margot A; Babovic-Vuksanovic, Dusica; Riegert-Johnson, Douglas L; Gavrilova, Ralitza H; McAllister, Tammy M; Lindor, Noralane M; Abraham, Roshini S; Ackerman, Michael J; Pichurin, Pavel N; Deyle, David R; Gavrilov, Dimitar K; Hand, Jennifer L; Klee, Eric W; Stephens, Michael C; Wick, Myra J; Atkinson, Elizabeth J; Linden, David R; Ferber, Matthew J; Wieben, Eric D; Farrugia, Gianrico

2016-03-01

To describe the experience and outcome of performing whole-exome sequencing (WES) for resolution of patients on a diagnostic odyssey in the first 18 months of an individualized medicine clinic (IMC). The IMC offered WES to physicians of Mayo Clinic practice for patients with suspected genetic disease. DNA specimens of the proband and relatives were submitted to WES laboratories. We developed the Genomic Odyssey Board with multidisciplinary expertise to determine the appropriateness for IMC services, review WES reports, and make the final decision about whether the exome findings explain the disease. This study took place from September 30, 2012, to March 30, 2014. In the first 18 consecutive months, the IMC received 82 consultation requests for patients on a diagnostic odyssey. The Genomic Odyssey Board deferred 7 cases and approved 75 cases to proceed with WES. Seventy-one patients met with an IMC genomic counselor. Fifty-one patients submitted specimens for WES testing, and the results have been received for all. There were 15 cases in which a diagnosis was made on the basis of WES findings; thus, the positive diagnostic yield of this practice was 29%. The mean cost per patient for this service was approximately $8000. Medicaid supported 27% of the patients, and 38% of patients received complete or partial insurance coverage. The significant diagnostic yield, moderate cost, and notable health marketplace acceptance for WES compared with conventional genetic testing make the former method a rational diagnostic approach for patients on a diagnostic odyssey. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Feasibility study of structured diagnosis methods for functional dyspepsia in Korean medicine clinics.

PubMed

Park, Jeong Hwan; Kim, Soyoung; Park, Jae-Woo; Ko, Seok-Jae; Lee, Sanghun

2017-12-01

Functional dyspepsia (FD) is the seventh most common disease encountered in Korean medicine (KM) clinics. Despite the large number of FD patients visiting KM clinics, the accumulated medical records have no utility in evidence development, due to being unstructured. This study aimed to construct a standard operating procedure (SOP) with appropriate structured diagnostic methods for FD, and assess the feasibility for use in KM clinics. Two rounds of professional surveys were conducted by 10 Korean internal medicine professors to select the representative diagnostic methods. A feasibility study was conducted to evaluate compliance and time required for using the structured diagnostic methods by three specialists in two hospitals. As per the results of the professional survey, five questionnaires and one basic diagnostic method were selected. An SOP was constructed based on the survey results, and a feasibility study showed that the SOP compliance score (out of 5) was 3.45 among the subjects, and 3.25 among the practitioners. The SOP was acceptable and was not deemed difficult to execute. The total execution time was 136.5 minutes, out of which the gastric emptying test time was 129 minutes. This feasibility study of the SOP with structured diagnostic methods for FD confirmed it was adequate for use in KM clinics. It is expected that these study findings will be helpful to clinicians who wish to conduct observational studies as well as to generate quantitative medical records to facilitate Big Data research.

Clinical Application of the UK Working Party's Criteria for the Diagnosis of Atopic Dermatitis in the Chinese Population by Age Group.

PubMed

Wang, Li; Li, Lin-Feng

2016-12-05

Atopic dermatitis (AD) is a common inflammatory skin disease with an increasingly significant prevalence. The prevalence of AD depends greatly on how its diagnosis is done. The UK Working Party's diagnostic criteria for AD are simple and easy to apply without invasive laboratory tests. This study assessed the clinical utility of these criteria in China. Data were collected from 6208 patients at 31 tertiary hospitals in 13 Chinese provinces/municipalities from March 2014 to May 2014. . The agreement between the UK diagnostic criteria and the clinical records for AD was assessed by Cohen's kappa. The overall agreement between the UK diagnostic criteria and clinical diagnosis was fair (kappa = 0.40). A slightly better agreement was found in patients aged between 4 and 9 years (kappa = 0.48), while fair agreement was found in the group <4 years and the group ≥10 years (kappa = 0.27 and 0.39, respectively). Using the UK party's criteria as the standard, the sensitivity, specificity, positive predictive value, and negative predictive value of the clinical diagnosis of AD were 62.3%, 89.2%, 38.0%, and 95.7%, respectively. Our study indicates a modest ability among Chinese dermatologists to apply the UK Working Party's diagnostic criteria for AD, especially in patients aged <4 years and ≥10 years. Since there is no gold standard for AD diagnosis, it is important to determine how AD is identified when evaluating a diagnostic tool.

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2018-01-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2017-05-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical benefits, ethics, and economics of stratified medicine and companion diagnostics.

PubMed

Trusheim, Mark R; Berndt, Ernst R

2015-12-01

The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified medicines in autoimmune, cardiovascular, neurodegenerative, respiratory, and other conditions. Of 53 oncology targets with a launched therapeutic, 44 have competing therapeutics. Only 12 of 141 Phase III candidates addressing new targets face no competition. CDx choices might alter competitive positions and reimbursement. Under current diagnostic incentives, payers see novel stratified medicines that improve public health and increase costs, but do not observe companion diagnostics for legacy treatments that would reduce costs. It would be in the interests of payers to rediscover their heritage of direct investment in diagnostic development. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Is evidence-based assessment fact or fiction? A bibliometric analysis of three German journals].

PubMed

Petermann, Franz; Schüssler, Gerhard; Glaesmer, Heide

2008-01-01

Despite the ongoing process for the development and dissemination of empirically supported treatments, little attention has been paid to the development of evidence-based diagnostics. The article aims at evaluating diagnostic procedures and instruments in current clinical research in terms of evidence-based assessment. Volumes 2006 and 2007 of three German psychological journals "Psychotherapeut," "Psychotherapie, Psychosomatik und Medizinische Psychologie," and "Zeitschrift für Psychiatrie, Psychologie und Psychotherapie" were screened for empirical reports and articles dealing with diagnostic issues. 93 articles were identified and evaluated. Most studies used psychometrically valid and established instruments for assessment. However, diagnostic interviews were relatively scarce, as were multimodal assessments. Measures used for outcome evaluation often lacked evidence of sensitivity to change. Clinical assessment to date does not meet criteria for evidence-based diagnostics. Implications for research and guideline development are discussed.

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

PubMed

Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis.

PubMed

Fischer, Joachim E; Bachmann, Lucas M; Jaeschke, Roman

2003-07-01

One of the most challenging practical and daily problems in intensive care medicine is the interpretation of the results from diagnostic tests. In neonatology and pediatric intensive care the early diagnosis of potentially life-threatening infections is a particularly important issue. A plethora of tests have been suggested to improve diagnostic decision making in the clinical setting of infection which is a clinical example used in this article. Several criteria that are critical to evidence-based appraisal of published data are often not adhered to during the study or in reporting. To enhance the critical appraisal on articles on diagnostic tests we discuss various measures of test accuracy: sensitivity, specificity, receiver operating characteristic curves, positive and negative predictive values, likelihood ratios, pretest probability, posttest probability, and diagnostic odds ratio. We suggest the following minimal requirements for reporting on the diagnostic accuracy of tests: a plot of the raw data, multilevel likelihood ratios, the area under the receiver operating characteristic curve, and the cutoff yielding the highest discriminative ability. For critical appraisal it is mandatory to report confidence intervals for each of these measures. Moreover, to allow comparison to the readers' patient population authors should provide data on study population characteristics, in particular on the spectrum of diseases and illness severity.

Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

PubMed

Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

2017-04-01

Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical Decision Rules for Diagnostic Imaging in the Emergency Department: A Research Agenda.

PubMed

Finnerty, Nathan M; Rodriguez, Robert M; Carpenter, Christopher R; Sun, Benjamin C; Theyyunni, Nik; Ohle, Robert; Dodd, Kenneth W; Schoenfeld, Elizabeth M; Elm, Kendra D; Kline, Jeffrey A; Holmes, James F; Kuppermann, Nathan

2015-12-01

Major gaps persist in the development, validation, and implementation of clinical decision rules (CDRs) for diagnostic imaging. The objective of this working group and article was to generate a consensus-based research agenda for the development and implementation of CDRs for diagnostic imaging in the emergency department (ED). The authors followed consensus methodology, as outlined by the journal Academic Emergency Medicine (AEM), combining literature review, electronic surveys, telephonic communications, and a modified nominal group technique. Final discussions occurred in person at the 2015 AEM consensus conference. A research agenda was developed, prioritizing the following questions: 1) what are the optimal methods to justify the derivation and validation of diagnostic imaging CDRs, 2) what level of evidence is required before disseminating CDRs for widespread implementation, 3) what defines a successful CDR, 4) how should investigators best compare CDRs to clinical judgment, and 5) what disease states are amenable (and highest priority) to development of CDRs for diagnostic imaging in the ED? The concepts discussed herein demonstrate the need for further research on CDR development and implementation regarding diagnostic imaging in the ED. Addressing this research agenda should have direct applicability to patients, clinicians, and health care systems. © 2015 by the Society for Academic Emergency Medicine.

Integrating molecular diagnostics into histopathology training: the Belfast model.

PubMed

Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

2014-07-01

Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical and diagnostic aspects of lymphedema.

PubMed

Keo, Hong H; Gretener, Silvia B; Staub, Daniel

2017-07-01

Lymphedema is a chronic, progressive, and common but often unrecognized condition. The diagnosis of lymphatic disease on clinical grounds alone remains a challenge. Without proper diagnosis, therapy is often delayed, allowing disease progression. There is a need for a practical diagnostic algorithm and its imaging technique to guide clinical decision-making. The aim of this topical review is to provide a practical approach for assessing patients with suspected lymphedema and to give a critical appraisal of currently available imaging modalities that are applied in clinical practice to diagnose and map lymphatic disease.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management.

PubMed

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-06-07

The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management

PubMed Central

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y.-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-01-01

Abstract The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians. PMID:29850820

Gold Nanoparticles for Diagnostics: Advances towards Points of Care

PubMed Central

Cordeiro, Mílton; Ferreira Carlos, Fábio; Pedrosa, Pedro; Lopez, António; Baptista, Pedro Viana

2016-01-01

The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor, most platforms have yet to reach maturity and make their way into clinics or points of care (POC). Here, we present an overview of emerging and available molecular diagnostics using AuNPs for biomedical sensing that are currently being translated to the clinical setting. PMID:27879660

Drug sensitivity testing platforms for gastric cancer diagnostics.

PubMed

Lau, Vianne; Wong, Andrea Li-Ann; Ng, Christopher; Mok, Yingting; Lakshmanan, Manikandan; Yan, Benedict

2016-02-01

Gastric cancer diagnostics has traditionally been histomorphological and primarily the domain of surgical pathologists. Although there is an increasing usage of molecular and genomic techniques for clinical diagnostics, there is an emerging field of personalised drug sensitivity testing. In this review, we describe the various personalised drug sensitivity testing platforms and discuss the challenges facing clinical adoption of these assays for gastric cancer. 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 outcomes and cost effectiveness of accelerated diagnostic protocol in a chest pain center compared with routine care of patients with chest pain.

PubMed

Asher, Elad; Reuveni, Haim; Shlomo, Nir; Gerber, Yariv; Beigel, Roy; Narodetski, Michael; Eldar, Michael; Or, Jacob; Hod, Hanoch; Shamiss, Arie; Matetzky, Shlomi

2015-01-01

The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department. Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14-0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)]. An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.

Clinical Outcomes and Cost Effectiveness of Accelerated Diagnostic Protocol in a Chest Pain Center Compared with Routine Care of Patients with Chest Pain

PubMed Central

Asher, Elad; Reuveni, Haim; Shlomo, Nir; Gerber, Yariv; Beigel, Roy; Narodetski, Michael; Eldar, Michael; Or, Jacob; Hod, Hanoch; Shamiss, Arie; Matetzky, Shlomi

2015-01-01

Aims The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department. Methods and Results Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14–0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)]. Conclusion An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources. PMID:25622029

Is there any evidence for the validity of diagnostic criteria used for accommodative and nonstrabismic binocular dysfunctions?

PubMed

Cacho-Martínez, Pilar; García-Muñoz, Ángel; Ruiz-Cantero, María Teresa

2014-01-01

To analyze the diagnostic criteria used in the scientific literature published in the past 25 years for accommodative and nonstrabismic binocular dysfunctions and to explore if the epidemiological analysis of diagnostic validity has been used to propose which clinical criteria should be used for diagnostic purposes. We carried out a systematic review of papers on accommodative and non-strabic binocular disorders published from 1986 to 2012 analysing the MEDLINE, CINAHL, PsycINFO and FRANCIS databases. We admitted original articles about diagnosis of these anomalies in any population. We identified 839 articles and 12 studies were included. The quality of included articles was assessed using the QUADAS-2 tool. The review shows a wide range of clinical signs and cut-off points between authors. Only 3 studies (regarding accommodative anomalies) assessed diagnostic accuracy of clinical signs. Their results suggest using the accommodative amplitude and monocular accommodative facility for diagnosing accommodative insufficiency and a high positive relative accommodation for accommodative excess. The remaining 9 articles did not analyze diagnostic accuracy, assessing a diagnosis with the criteria the authors considered. We also found differences between studies in the way of considering patients' symptomatology. 3 studies of 12 analyzed, performed a validation of a symptom survey used for convergence insufficiency. Scientific literature reveals differences between authors according to diagnostic criteria for accommodative and nonstrabismic binocular dysfunctions. Diagnostic accuracy studies show that there is only certain evidence for accommodative conditions. For binocular anomalies there is only evidence about a validated questionnaire for convergence insufficiency with no data of diagnostic accuracy. Copyright © 2012 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Lessons learned developing a diagnostic tool for HIV-associated dementia feasible to implement in resource-limited settings: pilot testing in Kenya.

PubMed

Kwasa, Judith; Cettomai, Deanna; Lwanya, Edwin; Osiemo, Dennis; Oyaro, Patrick; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire L

2012-01-01

To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/µL, and 54% had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K = .03-.65). This diagnostic tool had moderate sensitivity and specificity for HAD. However, reliability was poor, suggesting that substantial training and formal evaluations of training adequacy will be critical to enable HCW to reliably administer a brief diagnostic tool for HAD.

HFE gene in primary and secondary hepatic iron overload

PubMed Central

Sebastiani, Giada; Walker, Ann P

2007-01-01

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non-alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis. PMID:17729389

Structure and function of enzymes in heme biosynthesis.

PubMed

Layer, Gunhild; Reichelt, Joachim; Jahn, Dieter; Heinz, Dirk W

2010-06-01

Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the "Radical SAM enzyme" coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure-function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

The neuropsychiatric ailment of Vincent Van Gogh

PubMed Central

Bhattacharyya, Kalyan B.; Rai, Saurabh

2015-01-01

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Features such as hypergraphia, atypical sexuality, and viscosity of thinking suggest the possibility of Gastaut-Geschwind phenomenon, a known complication of complex partial seizure. On the contrary, some historians feel that he was forced to sever his right ear in order to get relief from troublesome tinnitus, a complication of Ménière's disease. He was addicted to the liquor absinthe, which is known to lead to xanthopsia, and many authorities argue that this was the reason for his penchant for the deep and bright yellow color in many of his paintings. Others have suggested the possibility of bipolar disorder, sunstroke, acute intermittent porphyria, and digitalis toxicity as well. PMID:25745302

A closer look at diagnosis in clinical dental practice: part 1. Reliability, validity, specificity and sensitivity of diagnostic procedures.

PubMed

Pretty, Iain A; Maupomé, Gerardo

2004-04-01

Dentists are involved in diagnosing disease in every aspect of their clinical practice. A range of tests, systems, guides and equipment--which can be generally referred to as diagnostic procedures--are available to aid in diagnostic decision making. In this era of evidence-based dentistry, and given the increasing demand for diagnostic accuracy and properly targeted health care, it is important to assess the value of such diagnostic procedures. Doing so allows dentists to weight appropriately the information these procedures supply, to purchase new equipment if it proves more reliable than existing equipment or even to discard a commonly used procedure if it is shown to be unreliable. This article, the first in a 6-part series, defines several concepts used to express the usefulness of diagnostic procedures, including reliability and validity, and describes some of their operating characteristics (statistical measures of performance), in particular, specificity and sensitivity. Subsequent articles in the series will discuss the value of diagnostic procedures used in daily dental practice and will compare today's most innovative procedures with established methods.

Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein

PubMed Central

Tang, Yin-Liang; Chiu, Chien-Yu; Lin, Chun-Yu; Huang, Chung-Hao; Chen, Yen-Hsu; Destura, Raul V.; Chao, Day-Yu; Wu, Han-Chung

2015-01-01

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients. PMID:26610481

Utilization of flow cytometry for diagnosis of hematologic malignancies in Thailand: increasing trends and diagnostic yields in 7,982 samples.

PubMed

Promsuwicha, Orathai; Kankhao, Supattra; Songmuang, Wayuree; Auewarakul, Chirayu U

2014-12-01

Diagnosis of hematologic malignancies requires a multidisciplinary approach. Flow cytometry (FCM) has become an essential tool for immunophenotypic studies of malignant hematopoietic cells. To evaluate the utilization trend of FCM and its diagnostic yields for hematologic malignancy at a major teaching hospital in Thailand. FCM results of bone marrow (BM) and peripheral blood (PB) specimens during 2000-2013 were analyzed and compared to clinical diagnosis. Overall, 7,982 specimens were submitted for diagnostic FCM including 6,561 BM and 1,421 PB. The number of specimens analyzedwas 121, 142, 164, 299, 491, 431, 690, 611, 719, 744, 725, 863, 955 and 1,027, respectively, from 2000 to 2013. The most common clinical diagnoses requested for FCM were acute leukemia (5,911 cases, 74%) followed by lymphoma (1,419 cases, 17.8%), and chronic lymphocytic leukemia (CLL) (634 cases, 7.94%). The highest diagnostic yield of FCM was found in acute leukemia cases (69.71%) followed by CLL (35.33%). Only 15.43% of clinically suspected lymphoma cases were positive by FCM. Overutilization of PB (35.6% of cases) instead of BM for lymphoma staging significantly contributed to low diagnostic yields of lymphoma by FCM as circulating tumor cells may not be present in such cases. FCM has an increasing role in the diagnosis of hematologic malignancies in Thai patients over the past 14 years with the highest diagnostic yield in acute leukemia. Appropriate specimen types and study indications are required in order to reduce futility of costly diagnostic tests and improve diagnostic yields.

Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review.

PubMed

Fenske, Wiebke; Allolio, Bruno

2012-10-01

The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term "polyuria polydipsia syndrome" was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.

The Spanish Diagnostic Interview Schedule. Reliability and comparison with clinical diagnoses.

PubMed

Burnam, M A; Karno, M; Hough, R L; Escobar, J I; Forsythe, A B

1983-11-01

The National Institute of Mental Health Diagnostic Interview Schedule (DIS) was translated into Spanish. The reliability of the Spanish instrument, its equivalence to the English version, and its agreement with clinical diagnoses were examined in a study of 90 bilingual (English-and Spanish-speaking) and 61 monolingual (Spanish-speaking only) patients from a community mental health center. The study design involved two independent DIS administrations and one independent clinical evaluation of each subject.

A systematic review of the PTSD Checklist's diagnostic accuracy studies using QUADAS.

PubMed

McDonald, Scott D; Brown, Whitney L; Benesek, John P; Calhoun, Patrick S

2015-09-01

Despite the popularity of the PTSD Checklist (PCL) as a clinical screening test, there has been no comprehensive quality review of studies evaluating its diagnostic accuracy. A systematic quality assessment of 22 diagnostic accuracy studies of the English-language PCL using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment tool was conducted to examine (a) the quality of diagnostic accuracy studies of the PCL, and (b) whether quality has improved since the 2003 STAndards for the Reporting of Diagnostic accuracy studies (STARD) initiative regarding reporting guidelines for diagnostic accuracy studies. Three raters independently applied the QUADAS tool to each study, and a consensus among the 4 authors is reported. Findings indicated that although studies generally met standards in several quality areas, there is still room for improvement. Areas for improvement include establishing representativeness, adequately describing clinical and demographic characteristics of the sample, and presenting better descriptions of important aspects of test and reference standard execution. Only 2 studies met each of the 14 quality criteria. In addition, study quality has not appreciably improved since the publication of the STARD Statement in 2003. Recommendations for the improvement of diagnostic accuracy studies of the PCL are discussed. (c) 2015 APA, all rights reserved).

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

76 FR 76736 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

... Project Survey of Rapid Influenza Diagnostic Test (RIDT) Practices in Laboratories-NEW--the Office of...). Background and Brief Description The Survey of Rapid Influenza Diagnostic Testing Practices in Laboratories is a national systematic study investigating rapid influenza diagnostic testing practices in clinical...

The Effect of Self-Explanation of Pathophysiological Mechanisms of Diseases on Medical Students' Diagnostic Performance

ERIC Educational Resources Information Center

Peixoto, José Maria; Mamede, Sílvia; de Faria, Rosa Malena Delbone; Moura, Alexandre Sampaio; Santos, Silvana Maria Elói; Schmidt, Henk G.

2017-01-01

Self-explanation while diagnosing clinical cases fosters medical students' diagnostic performance. In previous studies on self-explanation, students were free to self-explain any aspect of the case, and mostly clinical knowledge was used. Elaboration on knowledge of pathophysiological mechanisms of diseases has been largely unexplored in studies…

76 FR 28990 - Ultra High Throughput Sequencing for Clinical Diagnostic Applications-Approaches To Assess...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

...: 900). If you have never attended a Connect Pro meeting before, test your connection at: https://collaboration.fda.gov/common/help/en/support/meeting_test.htm . To get a quick overview of the Connect Pro... technologies are currently extensively used in research and are entering clinical diagnostic use; they are...

Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P).

PubMed

Ventura, J; Liberman, R P; Green, M F; Shaner, A; Mintz, J

1998-06-15

Accuracy in psychiatric diagnosis is critical for evaluating the suitability of the subjects for entry into research protocols and for establishing comparability of findings across study sites. However, training programs in the use of diagnostic instruments for research projects are not well systematized. Furthermore, little information has been published on the maintenance of interrater reliability of diagnostic assessments. At the UCLA Research Center for Major Mental Illnesses, a Training and Quality Assurance Program for SCID interviewers was used to evaluate interrater reliability and diagnostic accuracy. Although clinically experienced interviewers achieved better interrater reliability and overall diagnostic accuracy than neophyte interviewers, both groups were able to achieve and maintain high levels of interrater reliability, diagnostic accuracy, and interviewer skill. At the first quality assurance check after training, there were no significant differences between experienced and neophyte interviewers in interrater reliability or diagnostic accuracy. Standardization of training and quality assurance procedures within and across research projects may make research findings from study sites more comparable.

Selling biotechnology in the dental medicine marketplace: the OmniGene Diagnostics DNA probe tests for periodontal pathogens.

PubMed

Van Arsdell, S W; DiFronzo, F; Backman, K C; Mahler, P H

1996-09-01

OmniGene Diagnostics, Inc. has applied the principles of genetic engineering to develop species-specific DNA probe tests for eight periodontal pathogens (Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetem-comitans, Fusobacterium nucleatum, Eikenella corrodens, Campylobacter rectus, Bacteroides forsythus, and Treponema denticola). The test requires minimal effort on the part of the clinician: subgingival plaque samples are collected from the patient and sent through the mail for analysis by OmniGene Diagnostics' fully licensed clinical reference laboratory. Results are transmitted to the practitioner by phone, fax, or mail. The use of diagnostic tests for periodontal pathogens is a relatively new concept in dentistry and acceptance of the OmniGene Diagnostics tests by the dental marketplace has been slower than anticipated. OmniGene Diagnostics' challenge for the future is to persuade the dental community that monitoring periodontal pathogen levels, as well as other clinical indicators of disease, is essential to providing optimal care to the periodontitis patient.

Clinical proteomics: Applications for prostate cancer biomarker discovery and detection.

PubMed

Petricoin, Emanuel F; Ornstein, David K; Liotta, Lance A

2004-01-01

The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. Copyright 2004 Elsevier Inc.

Diagnostic laryngeal electromyography: The Wake Forest experience 1995-1999.

PubMed

Koufman, J A; Postma, G N; Whang, C S; Rees, C J; Amin, M R; Belafsky, P C; Johnson, P E; Connolly, K M; Walker, F O

2001-06-01

Laryngeal electromyography (LEMG) is a valuable diagnostic/prognostic test for patients with suspected laryngeal neuromuscular disorders. To report our experience with diagnostic LEMG at the Center for Voice Disorders of Wake Forest University and to evaluate the impact of LEMG on clinical management. Retrospective chart review of 415 patients who underwent diagnostic LEMG over a 5-year period (1995-1999). Of 415 studies, 83% (346 of 415) were abnormal, indicating a neuropathic process. LEMG results altered the diagnostic evaluation (eg, the type of radiographic imaging) in 11% (46 of 415) of the patients. Unexpected LEMG findings (eg, contralateral neuropathy) were found in 26% (107 of 415) of the patients, and LEMG results differentiated vocal fold paralysis from fixation in 12% (49 of 415). Finally, LEMG results altered the clinical management (eg, changed the timing and/or type of surgical procedure) in 40% (166 of 415) of the patients. LEMG is a valuable diagnostic test that aids the clinician in the diagnosis and management of laryngeal neuromuscular disorders.

Nucleic acid-based diagnostics for infectious diseases in public health affairs.

PubMed

Yu, Albert Cheung-Hoi; Vatcher, Greg; Yue, Xin; Dong, Yan; Li, Mao Hua; Tam, Patrick H K; Tsang, Parker Y L; Wong, April K Y; Hui, Michael H K; Yang, Bin; Tang, Hao; Lau, Lok-Ting

2012-06-01

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

Dissecting aneurysms of posterior communicating artery itself: anatomical, diagnostic, clinical, and therapeutical considerations.

PubMed

Kocak, Burak; Tureci, Ercan; Kizilkilic, Osman; Islak, Civan; Kocer, Naci

2013-09-01

Posterior communicating artery (PCoA) itself is an unusual location for intracranial aneurysms in that isolated dissections or dissecting aneurysms are extremely rare. In the way of correct diagnosis of dissecting aneurysms of PCoA itself, a proper understanding of (1) the anatomy of the PCoA and its perforator branches, (2) some particular diagnostic features, and (3) related clinical aspects is of significant importance. Although there are no established treatment strategies for this particular type of aneurysms, the endovascular approach might be considered as a plausible one. In this paper, our scope was to report five cases with dissecting aneurysm of the PCoA itself and to discuss this rare vascular pathology from anatomical, diagnostic, clinical, and therapeutical perspectives.

Clinically relevant advances in on-chip affinity-based electrophoresis and electrochromatography.

PubMed

Hou, Chenlu; Herr, Amy E

2008-08-01

Clinical and point-of-care disease diagnostics promise to play an important role in personalized medicine, new approaches to global health, and health monitoring. Emerging instrument platforms based on lab-on-a-chip technology can confer performance advantages successfully exploited in electrophoresis and electrochromatography to affinity-based electrokinetic separations. This review surveys lab-on-a-chip diagnostic developments in affinity-based electrokinetic separations for quantitation of proteins, integration of preparatory functions needed for subsequent analysis of diverse biological samples, and initial forays into multiplexed analyses. The technologies detailed here underpin new clinical and point-of-care diagnostic strategies. The techniques and devices promise to advance translation of until now laboratory-based sample preparation and analytical assays to near-patient settings.

Strategies for Optimizing the Diagnostic Predictive Value of Clostridium difficile Molecular Diagnostics.

PubMed

Kociolek, Larry K

2017-05-01

Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology , Truong et al. (J. Clin. Microbiol., 55:1276-1284, 2017, https://doi.org/10.1128/JCM.02319-16) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use. Copyright © 2017 American Society for Microbiology.

Case series of diagnostic shift from bipolar disorder to schizoaffective disorder.

PubMed

Argolo, Lucas; Batista, Fabrício; Bezerra-Filho, Severino; Kapczinski, Flávio; Miranda-Scippa, Ângela

2018-04-01

To describe three cases of diagnostic shift from bipolar I disorder (BD) to schizoaffective disorder (SAD). BD patients were clinically assessed and followed up in a mood disorder program. A questionnaire was applied to assess clinical and socio-demographic characteristics, and a Structured Clinical Interview (SCID-I) was conducted. We identified three patients with diagnosis conversion to SAD from 2005 to 2016. The mean time between BD diagnosis and the diagnostic shift to SAD was 9 years. Psychotic symptoms may become persistent, chronic and unrelated to the presence of mood episodes many years after the beginning of BD. Psychiatrists should be aware of this and reassess the diagnosis during the longitudinal course of BD, especially in those patients who present psychotic symptoms.

Massive Broad Ligament Cellular Leiomyoma with Cystic Change: A Diagnostic Dilemma.

PubMed

Sharma, Preeti; Zaheer, Sufian; Yadav, Amit Kumar; Mandal, Ashish Kumar

2016-04-01

Leiomyomas are known to arise from uterus, but rarely from broad ligament. Further, cellular leiomyoma of broad ligament is the least common variant reported in literature. The diagnostic dilemma arises when leiomyomas undergo degenerative changes. This poses both clinical and radiological difficulty in differentiating with an ovarian tumour. We present an unusual case of a huge broad ligament mass measuring 29x19x09cm, mimicking an ovarian tumour both clinically and radiologically. Histopathology revealed cellular leiomyoma of broad ligament with cystic and myxoid degeneration hereby being the second case reported in literature. This case is being presented not only because of the rare incidence but also due to its diagnostic confusion with ovarian malignancy on clinical evaluation and radiological findings.

Contextual factors and clinical reasoning: differences in diagnostic and therapeutic reasoning in board certified versus resident physicians.

PubMed

McBee, Elexis; Ratcliffe, Temple; Picho, Katherine; Schuwirth, Lambert; Artino, Anthony R; Yepes-Rios, Ana Monica; Masel, Jennifer; van der Vleuten, Cees; Durning, Steven J

2017-11-15

The impact of context on the complex process of clinical reasoning is not well understood. Using situated cognition as the theoretical framework and videos to provide the same contextual "stimulus" to all participants, we examined the relationship between specific contextual factors on diagnostic and therapeutic reasoning accuracy in board certified internists versus resident physicians. Each participant viewed three videotaped clinical encounters portraying common diagnoses in internal medicine. We explicitly modified the context to assess its impact on performance (patient and physician contextual factors). Patient contextual factors, including English as a second language and emotional volatility, were portrayed in the videos. Physician participant contextual factors were self-rated sleepiness and burnout.. The accuracy of diagnostic and therapeutic reasoning was compared with covariates using Fisher Exact, Mann-Whitney U tests and Spearman Rho's correlations as appropriate. Fifteen board certified internists and 10 resident physicians participated from 2013 to 2014. Accuracy of diagnostic and therapeutic reasoning did not differ between groups despite residents reporting significantly higher rates of sleepiness (mean rank 20.45 vs 8.03, U = 0.5, p < .001) and burnout (mean rank 20.50 vs 8.00, U = 0.0, p < .001). Accuracy of diagnosis and treatment were uncorrelated (r = 0.17, p = .65). In both groups, the proportion scoring correct responses for treatment was higher than the proportion scoring correct responses for diagnosis. This study underscores that specific contextual factors appear to impact clinical reasoning performance. Further, the processes of diagnostic and therapeutic reasoning, although related, may not be interchangeable. This raises important questions about the impact that contextual factors have on clinical reasoning and provides insight into how clinical reasoning processes in more authentic settings may be explained by situated cognition theory.

[Definition of the Diagnosis Osteomyelitis-Osteomyelitis Diagnosis Score (ODS)].

PubMed

Schmidt, H G K; Tiemann, A H; Braunschweig, R; Diefenbeck, M; Bühler, M; Abitzsch, D; Haustedt, N; Walter, G; Schoop, R; Heppert, V; Hofmann, G O; Glombitza, M; Grimme, C; Gerlach, U-J; Flesch, I

2011-08-01

The disease "osteomyelitis" is characterised by different symptoms and parameters. Decisive roles in the development of the disease are played by the causative bacteria, the route of infection and the individual defense mechanisms of the host. The diagnosis is based on different symptoms and findings from the clinical history, clinical symptoms, laboratory results, diagnostic imaging, microbiological and histopathological analyses. While different osteomyelitis classifications have been published, there is to the best of our knowledge no score that gives information how sure the diagnosis "osteomyelitis" is in general. For any scientific study of a disease a valid definition is essential. We have developed a special osteomyelitis diagnosis score for the reliable classification of clinical, laboratory and technical findings. The score is based on five diagnostic procedures: 1) clinical history and risk factors, 2) clinical examination and laboratory results, 3) diagnostic imaging (ultrasound, radiology, CT, MRI, nuclear medicine and hybrid methods), 4) microbiology, and 5) histopathology. Each diagnostic procedure is related to many individual findings, which are weighted by a score system, in order to achieve a relevant value for each assessment. If the sum of the five diagnostic criteria is 18 or more points, the diagnosis of osteomyelitis can be viewed as "safe" (diagnosis class A). Between 8-17 points the diagnosis is "probable" (diagnosis class B). Less than 8 points means that the diagnosis is "possible, but unlikely" (class C diagnosis). Since each parameter can score six points at a maximum, a reliable diagnosis can only be achieved if at least 3 parameters are scored with 6 points. The osteomyelitis diagnosis score should help to avoid the false description of a clinical presentation as "osteomyelitis". A safe diagnosis is essential for the aetiology, treatment and outcome studies of osteomyelitis. © Georg Thieme Verlag KG Stuttgart · New York.

Comparative evaluation of neonatal bilirubin using Radiometer whole blood co-oximetry and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics.

PubMed

Lano, Ian Marie; Lyon, Andrew W; Wang, Li; Ruskin, Rob; Lyon, Martha E

2018-03-01

Clinically significant variation has been reported within and between plasma and whole blood total bilirubin methods used to identify neonates for whom clinical intervention for hyperbilirubinemia may be required. To evaluate total bilirubin measurements between the Radiometer whole blood co-oximeter and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics using neonatal specimens. Total bilirubin levels were analyzed by whole blood co-oximetry (Radiometer® ABL90). Specimens were centrifuged and plasma analyzed for total bilirubin with a diazo method (Roche Cobas® C-601) and a reflectance spectrophotometric BuBc dry film method (Ortho Clinical Diagnostics VITROS® 350). Results were evaluated by regression, Bland-Altman comparisons and t-tests. The patient correlation study yielded the following regression equations in μmol/L: a) Radiometer=1.03 Roche - 3.5μmol/L b) Radiometer=0.98 Ortho - 5.7μmol/L c) Roche=0.97 Ortho - 2.4μmol/L. The mean bias over the range of total bilirubin levels examined was -1.0μmol/L for the Radiometer versus the Roche (p≤0.305); -4.4μmol/L for the Radiometer versus Ortho (p≤0.005) and -4.4μmol/L for the Roche versus Ortho (p≤0.002). Whole blood total bilirubin measurement using the Radiometer ABL90 blood gas analyzer provides accurate and precise results compared to the Roche plasma diazo method. Compared to the reflectance spectrophotometric method, results are precise and had a small but statistically significant bias of -4.4μmol/L. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Study protocol of the internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE), Korea, 2015-2019.

PubMed

Jeong, Hyunsuk; Yim, Hyeon Woo; Jo, Sun-Jin; Lee, Seung-Yup; Kim, Eunjin; Son, Hye Jung; Han, Hyun-Ho; Lee, Hae Kook; Kweon, Yong-Sil; Bhang, Soo-Young; Choi, Jung-Seok; Kim, Bung-Nyun; Gentile, Douglas A; Potenza, Marc N

2017-10-05

In 2013, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine internet gaming disorder (IGD) diagnostic criteria as a condition warranting further empirical and clinical research. The aim of this study is to clarify the natural and clinical courses of IGD proposed DSM-5 in adolescents and to evaluate its risk and protective factors. The Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence (iCURE) study is an ongoing multidisciplinary, prospective, longitudinal cohort study conducted in 21 schools in Korea. Participant recruitment commenced in March 2015 with the goal of registering 3000 adolescents. The baseline assessment included surveys on emotional, social and environmental characteristics. A parent or guardian completed questionnaires and a structured psychiatric comorbidity diagnostic interview regarding their children. Adolescents with the Internet Game Use-Elicited Symptom Screen total scores of 6 or higher were asked to participate in the clinical diagnostic interview. Two subcohorts of adolescents were constructed: a representative subcohort and a clinical evaluation subcohort. The representative subcohort comprises a randomly selected 10% of the iCURE to investigate the clinical course of IGD based on clinical diagnosis and to estimate the false negative rate. The clinical evaluation subcohort comprised participants meeting three or more of the nine IGD criteria, determined by clinical diagnostic interview, to show the clinical course of IGD. Follow-up data will be collected annually for the 3 years following the baseline assessments. The primary endpoint is 2-year incidence, remission and recurrence rates of IGD. Cross-sectional and longitudinal associations between exposures and outcomes as well as mediation factors will be evaluated. This study is approved by the Institutional Review Board of the Catholic University of Korea. Results will be published in peer-reviewed journals. ClinicalTrials.gov (identifier: NCT02415322). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Detecting fast, online reasoning processes in clinical decision making.

PubMed

Flores, Amanda; Cobos, Pedro L; López, Francisco J; Godoy, Antonio

2014-06-01

In an experiment that used the inconsistency paradigm, experienced clinical psychologists and psychology students performed a reading task using clinical reports and a diagnostic judgment task. The clinical reports provided information about the symptoms of hypothetical clients who had been previously diagnosed with a specific mental disorder. Reading times of inconsistent target sentences were slower than those of control sentences, demonstrating an inconsistency effect. The results also showed that experienced clinicians gave different weights to different symptoms according to their relevance when fluently reading the clinical reports provided, despite the fact that all the symptoms were of equal diagnostic value according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). The diagnostic judgment task yielded a similar pattern of results. In contrast to previous findings, the results of the reading task may be taken as direct evidence of the intervention of reasoning processes that occur very early, rapidly, and online. We suggest that these processes are based on the representation of mental disorders and that these representations are particularly suited to fast retrieval from memory and to making inferences. They may also be related to the clinicians' causal reasoning. The implications of these results for clinician training are also discussed.

Measurement Issues: Screening and diagnostic instruments for autism spectrum disorders – lessons from research and practice

PubMed Central

Charman, Tony; Gotham, Katherine

2012-01-01

Background and Scope Significant progress has been made over the past two decades in the development of screening and diagnostic instruments for autism spectrum disorders (ASD). This article reviews this progress, including recent innovations, focussing on those instruments for which the strongest research data on validity exists, and then turns to addressing issues arising from their use in clinical settings. Findings Research studies have evaluated the ability of screens to prospectively identify cases of ASD in population-based and clinically-referred samples, as well as the accuracy of diagnostic instruments to map onto ‘gold standard’ clinical best estimate diagnosis. However, extension of the findings to clinical services must be done with caution, with a full understanding that instrument properties are sample-specific. Furthermore, we are limited by the lack of a true test for ASD, which remains a behaviourally-defined disorder. In addition screening and diagnostic instruments help clinicians least in the cases where they are most in want of direction, since their accuracy will always be lower for marginal cases. Conclusion Instruments help clinicians to collect detailed, structured information and increase accuracy and reliability of referral for in-depth assessment and recommendations for support, but further research is needed to refine their effective use in clinical settings. PMID:23539140

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

PubMed

Niemantsverdriet, Ellis; Feyen, Bart F E; Le Bastard, Nathalie; Martin, Jean-Jacques; Goeman, Johan; De Deyn, Peter Paul; Bjerke, Maria; Engelborghs, Sebastiaan

2018-01-01

Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt. Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis. Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard neuropathological criteria and consisted of Alzheimer's disease (AD) or other dementias (NONAD). CSF levels of Aβ1 - 42, T-tau, and P-tau181 were determined and interpreted based on the IWG-2 and NIA-AA criteria, separately. A panel of three neurologists experienced with dementia made clinical consensus dementia diagnoses. Clinical and CSF biomarker diagnoses were compared to the autopsy-confirmed diagnoses. Forty-two patients (59%) had autopsy-confirmed AD, whereas 29 patients (41%) had autopsy-confirmed NONAD. Of the 24 patients with an ambiguous clinical dementia diagnosis, a correct diagnosis would have been established in 67% of the cases applying CSF biomarkers in the context of the IWG-2 or the NIA-AA criteria respectively. AD CSF biomarkers have an added diagnostic value in differential dementia diagnosis and can help establishing a correct dementia diagnosis in case of ambiguous clinical dementia diagnoses.

How to tell a patient's story? Influence of the case narrative design on the clinical reasoning process in virtual patients.

PubMed

Hege, Inga; Dietl, Anita; Kiesewetter, Jan; Schelling, Jörg; Kiesewetter, Isabel

2018-02-28

Virtual patients (VPs) are narrative-based educational activities to train clinical reasoning in a safe environment. Our aim was to explore the influence of the design of the narrative and level of difficulty on the clinical reasoning process, diagnostic accuracy and time-on-task. In a randomized controlled trial, we analyzed the clinical reasoning process of 46 medical students with six VPs in three different variations: (1) patients showing a friendly behavior, (2) patients showing a disruptive behavior and (3) a version without a patient story. For easy VPs, we did not see a significant difference in diagnostic accuracy. For difficult VPs, the diagnostic accuracy was significantly higher for participants who worked on the friendly VPs compared to the other two groups. Independent from VP difficulty, participants identified significantly more problems and tests for disruptive than for friendly VPs; time on task was comparable for these two groups. The extrinsic motivation of participants working on the VPs without a patient story was significantly lower than for the students working on the friendly VPs. Our results indicate that the measured VP difficulty has a higher influence on the clinical reasoning process and diagnostic accuracy than the variations in the narratives.

Diagnostic and interventional musculoskeletal ultrasound: part 2. Clinical applications.

PubMed

Smith, Jay; Finnoff, Jonathan T

2009-02-01

Musculoskeletal ultrasound involves the use of high-frequency sound waves to image soft tissues and bony structures in the body for the purposes of diagnosing pathology or guiding real-time interventional procedures. Recently, an increasing number of physicians have integrated musculoskeletal ultrasound into their practices to facilitate patient care. Technological advancements, improved portability, and reduced costs continue to drive the proliferation of ultrasound in clinical medicine. This increased interest creates a need for education pertaining to all aspects of musculoskeletal ultrasound. The primary purpose of this article is to review diagnostic ultrasound technology and its potential clinical applications in the evaluation and treatment of patients with neurological and musculoskeletal disorders. After reviewing this article, physicians should be able to (1) list the advantages and disadvantages of ultrasound compared to other available imaging modalities; (2) describe how ultrasound machines produce images using sound waves; (3) discuss the steps necessary to acquire and optimize an ultrasound image; (4) understand the difference ultrasound appearances of tendons, nerves, muscles, ligaments, blood vessels, and bones; and (5) identify multiple applications for diagnostic and interventional musculoskeletal ultrasound. Part 2 of this 2-part article will focus on the clinical applications of musculoskeletal ultrasound in clinical practice, including the ultrasonographic appearance of normal and abnormal tissues as well as specific diagnostic and interventional applications in major body regions.

Clinical Data as an Adjunct to Ultrasound Reduces the False-Negative Malignancy Rate in BI-RADS 3 Breast Lesions

PubMed Central

Ackermann, S.; Schoenenberger, C.-A.; Zanetti-Dällenbach, R.

2016-01-01

Purpose: Ultrasound (US) is a well-established diagnostic procedure for breast examination. We investigated the malignancy rate in solid breast lesions according to their BI-RADS classification with a particular focus on false-negative BI-RADS 3 lesions. We examined whether patient history and clinical findings could provide additional information that would help determine further diagnostic steps in breast lesions. Materials and Methods: We conducted a retrospective study by exploring US BI-RADS in 1469 breast lesions of 1201 patients who underwent minimally invasive breast biopsy (MIBB) from January 2002 to December 2011. Results: The overall sensitivity and specificity of BI-RADS classification was 97.4% and 66.4%, respectively, with a positive (PPV) and negative predictive value (NPV) of 65% and 98%, respectively. In 506 BI-RADS 3 lesions, histology revealed 15 malignancies (2.4% malignancy rate), which corresponds to a false-negative rate (FNR) of 2.6%. Clinical evaluation and patient requests critically influenced the further diagnostic procedure, thereby prevailing over the recommendation given by the BI-RADS 3 classification. Conclusion: Clinical criteria including age, family and personal history, clinical examination, mammography and patient choice ensure adequate diagnostic procedures such as short-term follow-up or MIBB in patients with lesions classified as US-BI-RADS 3. PMID:27689181

T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.

PubMed

Puntmann, Valentina O; Zeiher, Andreas M; Nagel, Eike

2018-05-01

Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.

Confetti-like Sparing

PubMed Central

Fitzpatrick, Richard E.; Goldman, Mitchel P.

2016-01-01

Diagnostic uncertainty when a patient presents with melasma-like Undings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the “Fitzpatrick macule” and test its Utility in establishing diagnostic certainty. The “Fitzpatrick macule” is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic Utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. PMID:27047632

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

Characteristics and Implications of Diagnostic Justification Scores Based on the New Patient Note Format of the USMLE Step 2 CS Exam.

PubMed

Yudkowsky, Rachel; Park, Yoon Soo; Hyderi, Abbas; Bordage, Georges

2015-11-01

To determine the psychometric characteristics of diagnostic justification scores based on the patient note format of the United States Medical Licensing Examination Step 2 Clinical Skills exam, which requires students to document history and physical findings, differential diagnoses, diagnostic justification, and plan for immediate workup. End-of-third-year medical students at one institution wrote notes for five standardized patient cases in May 2013 (n = 180) and 2014 (n = 177). Each case was scored using a four-point rubric to rate each of the four note components. Descriptive statistics and item analyses were computed and a generalizability study done. Across cases, 10% to 48% provided no diagnostic justification or had several missing or incorrect links between history and physical findings and diagnoses. The average intercase correlation for justification scores ranged from 0.06 to 0.16; internal consistency reliability of justification scores (coefficient alpha across cases) was 0.38. Overall, justification scores had the highest mean item discrimination across cases. The generalizability study showed that person-case interaction (12%) and task-case interaction (13%) had the largest variance components, indicating substantial case specificity. The diagnostic justification task provides unique information about student achievement and curricular gaps. Students struggled to correctly justify their diagnoses; performance was highly case specific. Diagnostic justification was the most discriminating element of the patient note and had the greatest variability in student performance across cases. The curriculum should provide a wide range of clinical cases and emphasize recognition and interpretation of clinically discriminating findings to promote the development of clinical reasoning skills.

Diagnostic Approach to Ocular Toxoplasmosis

PubMed Central

Garweg, Justus G; de Groot-Mijnes, Jolanda DF; Montoya, Jose G

2011-01-01

Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances. PMID:21770803

Clinical Predictors of Shigella and Campylobacter Infection in Children in the United States

PubMed Central

Smith, Timothy; Ye, Xiangyang; Stockmann, Chris; Cohen, Daniel; Leber, Amy; Daly, Judy; Jackson, Jami; Selvarangan, Rangaraj; Kanwar, Neena; Bender, Jeffery; Bard, Jennifer Dien; Festekjian, Ara; Duffy, Susan; Larsen, Chari; Baca, Tanya; Holmberg, Kristen; Bourzac, Kevin; Chapin, Kimberle C; Pavia, Andrew; Leung, Daniel

2017-01-01

Abstract Background Infectious gastroenteritis is a major cause of morbidity and mortality among children worldwide. While most episodes are self-limiting, for select pathogens such as Shigella and Campylobacter, etiological diagnosis may allow effective antimicrobial therapy and aid public health interventions. Unfortunately, clinical predictors of such pathogens are not well established and are based on small studies using bacterial culture for identification. Methods We used prospectively collected data from a multi-center study of pediatric gastroenteritis employing multi-pathogen molecular diagnostics to determine clinical predictors associated with 1) Shigella and 2) Shigella or Campylobacter infection. We used machine learning algorithms for clinical predictor identification, then performed logistic regression on features extracted plus pre-selected variables of interest. Results Of 993 children enrolled with acute diarrhea, we detected Shigella spp. in 56 (5.6%) and Campylobacter spp. in 24 (2.4%). Compared with children who had neither pathogen detected (of whom, >70% had ≥1 potential pathogen identified), bloody diarrhea (odds ratio 4.0), headache (OR 2.2), fever (OR 7.1), summer (OR 3.3), and sick contact with GI illness (OR 2.2), were positively associated with Shigella, and out-of-state travel (OR 0.3) and vomiting and/or nausea (OR 0.4) were negatively associated (Table). For Shigella or Campylobacter, predictors were similar but season was no longer significantly associated with infection. Conclusion These results can create prediction models and assist clinicians with identifying patients who would benefit from diagnostic testing and earlier antibiotic treatment. This may curtail unnecessary antibiotic use, and help to direct and target appropriate use of stool diagnostics. Disclosures A. Leber, BioFIre Diagnostics: Research Contractor and Scientific Advisor, Research support, Speaker honorarium and Travel expenses J. Daly, Biofire: Grant Investigator, Grant recipient R. Selvarangan, BioFire Diagnostics: Board Member and Investigator, Consulting fee and Research grant Luminex Diagnostics: Investigator, Research grant J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium K. Holmberg, BioFire Diagnostics: Employee, Salary K. Bourzac, BioFire Diagnostics: Employee, Salary K. C. Chapin, BioFire Diagnstics: Investigator, Research support A. Pavia, BioFire Diagnostics: Grant Investigator, Research grant

New DSM-V neurocognitive disorders criteria and their impact on diagnostic classifications of mild cognitive impairment and dementia in a memory clinic setting.

PubMed

Tay, Laura; Lim, Wee Shiong; Chan, Mark; Ali, Noorhazlina; Mahanum, Shariffah; Chew, Pamela; Lim, June; Chong, Mei Sian

2015-08-01

To examine diagnostic agreement between Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) Neurocognitive Disorders (NCDs) criteria and DSM, Fourth Edition (DSM-IV) criteria for dementia and International Working Group (IWG) criteria for mild cognitive impairment (MCI) and DSM-V's impact on diagnostic classifications of NCDs. The authors further examined clinical factors for discrepancy in diagnostic classifications between the different operational definitions. Using a cross-sectional study in tertiary memory clinic, the authors studied consecutive new patients aged 55 years or older who presented with cognitive symptoms. Dementia severity was scored based on the Clinical Dementia Rating scale (CDR). All patients completed neuropsychological evaluation. Agreement in diagnostic classifications between DSM-IV/IWG and DSM-V was examined using the kappa test and AC1 statistic, with multinomial logistic regression for factors contributing to MCI reclassification as major NCDs as opposed to diagnostically concordant MCI and dementia groups. Of 234 patients studied, 166 patients achieved concordant diagnostic classifications, with overall kappa of 0.41. Eighty-six patients (36.7%) were diagnosed with MCI and 131 (56.0%) with DSM-IV-defined dementia. With DSM-V, 40 patients (17.1%) were classified as mild NCDs and 183 (78.2%) as major NCDs, representing a 39.7% increase in frequency of dementia diagnoses. CDR sum-of-boxes score contributed independently to differentiation of MCI patients reclassified as mild versus major NCDs (OR: 0.01; 95% CI: 0-0.09). CDR sum-of-boxes score (OR: 5.18; 95% CI: 2.04-13.15), performance in amnestic (OR: 0.14; 95% CI: 0.06-0.34) and language (Boston naming: OR: 0.52; 95% CI: 0.29-0.94) tests, were independent determinants of diagnostically concordant dementia diagnosis. The authors observed moderate agreement between the different operational definitions and a 40% increase in dementia diagnoses with operationalization of the DSM-V criteria. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study.

PubMed

Luo, Yuan; Zhu, Xu; Zhang, Pengjun; Shen, Qian; Wang, Zi; Wen, Xinyu; Wang, Ling; Gao, Jing; Dong, Jin; Yang, Caie; Wu, Tangming; Zhu, Zheng; Tian, Yaping

2015-01-01

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance.

The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study

PubMed Central

Luo, Yuan; Zhu, Xu; Zhang, Pengjun; Shen, Qian; Wang, Zi; Wen, Xinyu; Wang, Ling; Gao, Jing; Dong, Jin; Yang, Caie; Wu, Tangming; Zhu, Zheng; Tian, Yaping

2015-01-01

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance. PMID:26884957

An ultra-low-cost smartphone octochannel spectrometer for mobile health diagnostics.

PubMed

Wang, Li-Ju; Naudé, Nicole; Chang, Yu-Chung; Crivaro, Anne; Kamoun, Malek; Wang, Ping; Li, Lei

2018-03-30

With the rapid development and proliferation of mobile devices with powerful computing power and the ability of integrating sensors into mobile devices, the potential impact of mobile health (mHealth) diagnostics on the public health is drawing researchers' attention. We developed a Smartphone Octo-channel Spectrometer (SOS) as a mHealth diagnostic tool. The SOS has nanoscale wavelength resolution, is self-illuminated from the smartphone itself, and is ultra-low cost (less than $20). A user interface controls the optical sensing parameters and precise alignment. After calibrating and testing the SOS by quantifying protein concentrations, we clinically validated the SOS by comparing the diagnostic performance of our device with that of a clinical spectrophotometer. About 180 serum samples from de-identified patients with 4 types of autoantibodies were blindly read the ELISA results. The accuracy of the SOS achieved 100% across the clinical reportable range compared with the FDA-approved instrument. Furthermore, the self-illuminated SOS only requires about half of the light intensity of the FDA-approved instrument to achieve clinical-level sensitivity. The low-energy-consumption and low-cost SOS enables point-of-care spectrophotometric sensing in low-resource areas, and can be integrated into point-of-care diagnostic systems for rapid multiplex readout and analysis at patient bedside or at home. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of pressure ulcer classification system education programme on knowledge and visual differential diagnostic ability of pressure ulcer classification and incontinence-associated dermatitis for clinical nurses in Korea.

PubMed

Lee, Yun Jin; Kim, Jung Yoon

2016-03-01

The objective of this study was to evaluate the effect of pressure ulcer classification system education on clinical nurses' knowledge and visual differential diagnostic ability of pressure ulcer (PU) classification and incontinence-associated dermatitis (IAD). One group pre and post-test was used. A convenience sample of 407 nurses, participating in PU classification education programme of continuing education, were enrolled. The education programme was composed of a 50-minute lecture on PU classification and case-studies. The PU Classification system and IAD knowledge test (PUCS-KT) and visual differential diagnostic ability tool (VDDAT), consisting of 21 photographs including clinical information were used. Paired t-test was performed using SPSS/WIN 20.0. The overall mean difference of PUCS-KT (t = -11·437, P<0·001) and VDDAT (t = -21·113, P<0·001) was significantly increased after PU classification education. Overall understanding of six PU classification and IAD after education programme was increased, but lacked visual differential diagnostic ability regarding Stage III PU, suspected deep tissue injury (SDTI), and Unstageable. Continuous differentiated education based on clinical practice is needed to improve knowledge and visual differential diagnostic ability for PU classification, and comparison experiment study is required to examine effects of education programmes. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Cognitive balanced model: a conceptual scheme of diagnostic decision making.

PubMed

Lucchiari, Claudio; Pravettoni, Gabriella

2012-02-01

Diagnostic reasoning is a critical aspect of clinical performance, having a high impact on quality and safety of care. Although diagnosis is fundamental in medicine, we still have a poor understanding of the factors that determine its course. According to traditional understanding, all information used in diagnostic reasoning is objective and logically driven. However, these conditions are not always met. Although we would be less likely to make an inaccurate diagnosis when following rational decision making, as described by normative models, the real diagnostic process works in a different way. Recent work has described the major cognitive biases in medicine as well as a number of strategies for reducing them, collectively called debiasing techniques. However, advances have encountered obstacles in achieving implementation into clinical practice. While traditional understanding of clinical reasoning has failed to consider contextual factors, most debiasing techniques seem to fail in raising sound and safer medical praxis. Technological solutions, being data driven, are fundamental in increasing care safety, but they need to consider human factors. Thus, balanced models, cognitive driven and technology based, are needed in day-to-day applications to actually improve the diagnostic process. The purpose of this article, then, is to provide insight into cognitive influences that have resulted in wrong, delayed or missed diagnosis. Using a cognitive approach, we describe the basis of medical error, with particular emphasis on diagnostic error. We then propose a conceptual scheme of the diagnostic process by the use of fuzzy cognitive maps. © 2011 Blackwell Publishing Ltd.

[Study of compatibility of psychiatric diagnoses with ICD-10 diagnostic criteria using the SCAN questionnaire].

PubMed

Adamowski, Tomasz; Kiejna, Andrzej; Hadryś, Tomasz

2006-01-01

Authors aimed at testing whether psychiatrists in their diagnostic process obeyed strict ICD-10 diagnostic criteria. Diagnoses made by psychiatrists at discharge were compared with those of SCAN ver.2.1 on admission. Diagnoses obtained by SCAN I-Shell program were compared with clinical diagnoses obtained by psychiatrists in the psychiatric wards according to ICD-10 criteria on 3 levels: diagnostic group (Fc), diagnostic class (Fcc), and diagnostic category (Fcc.c). Validity assessment was obtained with Cohen's Kappa coefficient, sensitivity, specificity and Yule's Y coefficient. On the diagnostic group level, Cohen's kappa was 0.14-0.65, Yule's Y 0.57-0.71. Sensitivity 0.69-0.95 and specificity 0.41-0.94. In psychotic disorders group F2 kappa was 0.65, Yule's Y 0.71, sensitivity 0.69, specificity 0.94. In affective disorders group F3 kappa was 0.31, Yule's Y 0.57, sensitivity 0.95, specificity 0.41. In neurotic disorders group F4 kappa was low 0.14, Yule's Y 0.62, sensitivity 0.95, specificity 0.50. The study showed a higher level of agreement between SCAN and clinical diagnoses in the group of psychotic disorders with exception of schizoaffective disorders, and lower agreement rates in the group of affective and neurotic disorders where the number of SCAN diagnoses outweighed that of the clinical ones. It could be the result of systematic faults in the coding of diagnoses.

An ontology-driven, diagnostic modeling system.

PubMed

Haug, Peter J; Ferraro, Jeffrey P; Holmen, John; Wu, Xinzi; Mynam, Kumar; Ebert, Matthew; Dean, Nathan; Jones, Jason

2013-06-01

To present a system that uses knowledge stored in a medical ontology to automate the development of diagnostic decision support systems. To illustrate its function through an example focused on the development of a tool for diagnosing pneumonia. We developed a system that automates the creation of diagnostic decision-support applications. It relies on a medical ontology to direct the acquisition of clinic data from a clinical data warehouse and uses an automated analytic system to apply a sequence of machine learning algorithms that create applications for diagnostic screening. We refer to this system as the ontology-driven diagnostic modeling system (ODMS). We tested this system using samples of patient data collected in Salt Lake City emergency rooms and stored in Intermountain Healthcare's enterprise data warehouse. The system was used in the preliminary development steps of a tool to identify patients with pneumonia in the emergency department. This tool was compared with a manually created diagnostic tool derived from a curated dataset. The manually created tool is currently in clinical use. The automatically created tool had an area under the receiver operating characteristic curve of 0.920 (95% CI 0.916 to 0.924), compared with 0.944 (95% CI 0.942 to 0.947) for the manually created tool. Initial testing of the ODMS demonstrates promising accuracy for the highly automated results and illustrates the route to model improvement. The use of medical knowledge, embedded in ontologies, to direct the initial development of diagnostic computing systems appears feasible.

Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

PubMed Central

Ade, Maria Paz; Baird, J. Kevin; Cheng, Qin; Cunningham, Jane; Dhorda, Mehul; Drakeley, Chris; Felger, Ingrid; Gamboa, Dionicia; Harbers, Matthias; Herrera, Socrates; Lucchi, Naomi; Mayor, Alfredo; Mueller, Ivo; Sattabongkot, Jetsumon; Ratsimbason, Arsène; Richards, Jack; Tanner, Marcel; González, Iveth J.

2017-01-01

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria. PMID:28369085

Diagnostic grand rounds: a new teaching concept to train diagnostic reasoning.

PubMed

Stieger, Stefan; Praschinger, Andrea; Kletter, Kurt; Kainberger, Franz

2011-06-01

Diagnostic reasoning is a core skill in teaching and learning in undergraduate curricula. Diagnostic grand rounds (DGRs) as a subform of grand rounds are intended to train the students' skills in the selection of appropriate tests and in the interpretation of test results. The aim of this study was to test DGRs for their ability to improve diagnostic reasoning by using a pre-post-test design. During one winter term, all 398 fifth-year students (36.1% male, 63.9% female) solved 23 clinical cases presented in 8 DGRs. In an online questionnaire, a Diagnostic Thinking Inventory (DTI) with 41 items was evaluated for flexibility in thinking and structure of knowledge in memory. Results were correlated with those from a summative multiple-choice knowledge test and of the learning objectives in a logbook. The students' DTI scores in the post-test were significantly higher than those reported in the pre-test. DTI scores at either testing time did not correlate with medical knowledge as assessed by a multiple-choice knowledge test. Abilities acquired during clinical clerkships as documented in a logbook could only account for a small proportion of the increase in the flexibility subscale score. This effect still remained significant after accounting for potential confounders. Establishing DGRs proofed to be an effective way of successfully improving both students' diagnostic reasoning and the ability to select the appropriate test method in routine clinical practice. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

How to: evaluate a diagnostic test.

PubMed

Leeflang, Mariska M G; Allerberger, Franz

2018-06-12

The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step. This article aims to summarize the necessary questions to be asked about a test and to illustrate study designs answering these questions. We also aim to relate the Regulation (EU) 2017/746 to the needs of evidence-based diagnostic testing, where applicable. We used literature on evidence-based diagnostics, a text book on clinical trials in the development and marketing of medical devices and the English version of Regulation 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices. The combination of different test uses and different stages of development determine the required test characteristics and suitability of study designs. In an earlier stage of test development it may be crucial to know whether a test can differentiate diseased persons from healthy controls, while this tells us little about how a test will perform in practice. Later stages focus on the diagnostic accuracy of a test in a clinically relevant situation. However, a test that perfectly distinguishes between patients with and without a certain condition may still have little effect on patient outcomes. Therefore, randomized controlled trials of testing may be needed, as well as post-marketing monitoring. Both researchers and users of tests need to be aware of the limitations of diagnostic test accuracy and realize that accuracy is only indirectly linked to people's health status. Copyright © 2018. Published by Elsevier Ltd.

Some Cognitive Components of the Diagnostic Thinking Process.

ERIC Educational Resources Information Center

Gale, Janet

1982-01-01

Identifies 14 cognitive components of the diagnostic thinking process in clinical problem solving. Analyzes the differences between medical students, hospital house officers, and hospital registrars in London, England, on the relative use of such thinking processes. Suggests that diagnostic thinking processes cannot be incorporated into medical…

Malaria rapid diagnostic tests.

PubMed

Wilson, Michael L

2012-06-01

Global efforts to control malaria are more complex than those for other infectious diseases, in part because of vector transmission, the complex clinical presentation of Plasmodium infections, >1 Plasmodium species causing infection, geographic distribution of vectors and infection, and drug resistance. The World Health Organization approach to global malaria control focuses on 2 components: vector control and diagnosis and treatment of clinical malaria. Although microscopy performed on peripheral blood smears remains the most widely used diagnostic test and the standard against which other tests are measured, rapid expansion of diagnostic testing worldwide will require use of other diagnostic approaches. This review will focus on the malaria rapid diagnostic test (MRDT) for detecting malaria parasitemia, both in terms of performance characteristics of MRDTs and how they are used under field conditions. The emphasis will be on the performance and use of MRDTs in regions of endemicity, particularly sub-Saharan Africa, where most malaria-related deaths occur.

Current challenges in diagnostic imaging of venous thromboembolism.

PubMed

Huisman, Menno V; Klok, Frederikus A

2015-01-01

Because the clinical diagnosis of deep-vein thrombosis and pulmonary embolism is nonspecific, integrated diagnostic approaches for patients with suspected venous thromboembolism have been developed over the years, involving both non-invasive bedside tools (clinical decision rules and D-dimer blood tests) for patients with low pretest probability and diagnostic techniques (compression ultrasound for deep-vein thrombosis and computed tomography pulmonary angiography for pulmonary embolism) for those with a high pretest probability. This combination has led to standardized diagnostic algorithms with proven safety for excluding venous thrombotic disease. At the same time, it has become apparent that, as a result of the natural history of venous thrombosis, there are special patient populations in which the current standard diagnostic algorithms are not sufficient. In this review, we present 3 evidence-based patient cases to underline recent developments in the imaging diagnosis of venous thromboembolism. © 2015 by The American Society of Hematology. All rights reserved.

[Chronic diarrhoea: Definition, classification and diagnosis].

PubMed

Fernández-Bañares, Fernando; Accarino, Anna; Balboa, Agustín; Domènech, Eugeni; Esteve, Maria; Garcia-Planella, Esther; Guardiola, Jordi; Molero, Xavier; Rodríguez-Luna, Alba; Ruiz-Cerulla, Alexandra; Santos, Javier; Vaquero, Eva

2016-10-01

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Interrelationship between Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) Classification in Children and Adolescents with Mental Retardation

ERIC Educational Resources Information Center

de Bildt, Annelies; Sytema, Sjoerd; Ketelaars, Cees; Kraijer, Dirk; Mulder, Erik; Volkmar, Fred; Minderaa, Ruud

2004-01-01

The interrelationship between the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule-Generic (ADOS-G) and clinical classification was studied in 184 children and adolescents with Mental Retardation (MR). The agreement between the ADI-R and ADOS-G was fair, with a substantial difference between younger and older…

Enabling Equal Access to Molecular Diagnostics: What Are the Implications for Policy and Health Technology Assessment?

PubMed

Plun-Favreau, Juliette; Immonen-Charalambous, Kaisa; Steuten, Lotte; Strootker, Anja; Rouzier, Roman; Horgan, Denis; Lawler, Mark

2016-01-01

Molecular diagnostics can offer important benefits to patients and are a key enabler of the integration of personalised medicine into health care systems. However, despite their promise, few molecular diagnostics are embedded into clinical practice (especially in Europe) and access to these technologies remains unequal across countries and sometimes even within individual countries. If research translation and the regulatory environments have proven to be more challenging than expected, reimbursement and value assessment remain the main barriers to providing patients with equal access to molecular diagnostics. Unclear or non-existent reimbursement pathways, together with the lack of clear evidence requirements, have led to significant delays in the assessment of molecular diagnostics technologies in certain countries. Additionally, the lack of dedicated diagnostics budgets and the siloed nature of resource allocation within certain health care systems have significantly delayed diagnostics commissioning. This article will consider the perspectives of different stakeholders (patients, health care payers, health care professionals, and manufacturers) on the provision of a research-enabled, patient-focused molecular diagnostics platform that supports optimal patient care. Through the discussion of specific case studies, and building on the experience from countries that have successfully integrated molecular diagnostics into clinical practice, this article will discuss the necessary evolutions in policy and health technology assessment to ensure that patients can have equal access to appropriate molecular diagnostics. © 2016 S. Karger AG, Basel.

Advances and challenges in biosensor-based diagnosis of infectious diseases

PubMed Central

Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

2014-01-01

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

Fluorescence analysis of ubiquinone and its application in quality control of medical supplies

NASA Astrophysics Data System (ADS)

Timofeeva, Elvira O.; Gorbunova, Elena V.; Chertov, Aleksandr N.

2017-02-01

The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of fluorescence analysis into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone is one of the steps for development of the device with a view to clinical diagnostics of redox potential. Recording of fluorescence was carried out with spectrometer using UV irradiation source with thin band (max at 287 and 330 nm) as a background radiation. Concentrations of ubiquinone from 0.25 to 2.5 mmol/l in explored samples were used for investigation. Recording data was processed using correlation analysis and differential analytical technique. The fourth derivative spectrum of fluorescence spectrum provided the basis for a multicomponent analysis of the solutions. As a technique in clinical diagnostics fluorescence analysis with processing method including differential spectrophotometry, it is step forward towards redox potential calculation and quality control in pharmacy for better health care.

Comparison of performance of computer display monitors for radiological diagnosis; "diagnostic" high brightness monochrome LCD, 3MP vs "clinical review" colour LCD, 2MP.

PubMed

Sim, L; Manthey, K; Stuckey, S

2007-06-01

A study to compare performance of the following display monitors for application as PACS CR diagnostic workstations is described. 1. Diagnostic quality, 3 Mega Pixel, 21 inch monochrome LCD monitors--Planar C3i. 2. Clinical review quality, 2 Mega Pixel, 21 inch colour LCD monitors--Planar PX212. Two sets of seventy radiological studies were presented to four senior radiologists on two occasions, using different displays on each occasion. The clinical condition used for this investigation was to query for the presence of a solitary pulmonary nodule. Receiver Operating Characteristic (ROC) curves were constructed for diagnostic performance for each presentation. Areas under the ROC curves (AUC) for diagnosis using different monitors were compared and the following results obtained: Monochrome AUC = 0.813 +/- 0.02, Colour AUC = 0.801 +/- 0.021. These results indicate that there is no statistically significant difference in the performance of these monitor types at a 95% confidence level.

Sensory processing issues in young children presenting to an outpatient feeding clinic.

PubMed

Davis, Ann M; Bruce, Amanda S; Khasawneh, Rima; Schulz, Trina; Fox, Catherine; Dunn, Winifred

2013-02-01

The aim of the study was to describe the relation between sensory issues and medical complexity in a series of patients presenting to an outpatient multidisciplinary feeding team for evaluation, by a standardized measure of sensory-processing abilities. A retrospective chart review of all of the patients seen from 2004 to 2009 on 2 key variables: medical diagnostic category and short sensory profile (SSP) score. On the SSP, 67.6% of children scored in the clinical ("definite difference") range. The most common diagnostic categories were developmental (n = 23), gastrointestinal (n = 16), and neurological (n = 13). Behavioral and cardiorespiratory medical diagnostic categories were significantly related to SSP total score and SSP definite difference score. Children who present for feeding evaluation do indeed tend to have clinically elevated scores regarding sensory processing, and these elevated scores are significantly related to certain medical diagnostic categories. Future research is needed to determine why these significant relations exist as well as their implications for treatment of feeding-related issues.

[The clinical manifestations and diagnostics of otitis media caused by tuberculosis].

PubMed

Kryukov, A I; Garov, E V; Ivoilov, A Yu; Shadrin, G B; Sidorina, N G; Lavrova, A S

2015-01-01

The objective of the present study was to clarify the characteristic pathognomonic features of middle ear lesions associated with tuberculosis and the approaches to their diagnostics under the present-day conditions. The study included 11 cases (18 ears) of tuberculosis otitis media and the related lesions of the mastoid process diagnosed with the use of clinical, roentgenological, cytological, bacteriological, pathomorphological, and molecular-genetic methods (including PCR diagnostics). The primary localization of tuberculosis in the middle ear was documented in 6 patients; in 5 patients, it was associated with pulmonary involvement. Five patients presented with smoldering exudative otitis media and the remaining six ones with suppurative perforating otitis media. The tuberculous process was diagnosed with the use of various methods including clinical examination, bacteriological (9%), cytological (27.3%), pathomorphological (18%) studies, and PCR diagnostics (55%). Diagnosis was made within a period from 1 month to 1.5 years after the application of the patients for medical assistance which suggests the difficulty of verification of tuberculous etiology of the disease of the middle ear. It is concluded that the high index of suspicion in the case of smoldering middle ear pathology facilitates its early diagnostics and successful treatment.

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Teledermatology consultation using a smartphone multimedia messaging service for common skin diseases in the Korean army: a clinical evaluation of its diagnostic accuracy.

PubMed

Shin, Hyoseung; Kim, Dong Hyun; Ryu, Hyeong Ho; Yoon, So Young; Jo, Seong Jin

2014-03-01

We evaluated the diagnostic accuracy of teleconsultations for skin diseases common in the army using a smartphone multimedia messaging service (MMS). Images of skin lesions were obtained from 100 army patients using digital cameras built into smartphones. Three remotely located dermatologists received the dermatology images and associated clinical information via the MMS. The teledermatologists' diagnoses were compared with those obtained from face-to-face examinations. The three most common diagnoses made at the dermatology clinics were eczema, viral warts and fungal infections. The mean diagnostic agreement between face-to-face and teledermatology consultations was 71% (SD 2). The mean kappa coefficient was 0.73 (SD 0.06) for the three most common diagnostic categories. The mean values for sensitivity were 78% (SD 0), 88% (SD 21) and 61% (SD 11) for eczema, viral warts and fungal infections, respectively, and the specificity values were above 90% for these skin diseases. Teledermatology consultation using smartphones is simple. Although diagnoses using telemedicine do not perfectly match diagnoses from face-to-face consultations the diagnostic accuracy using smartphones is superior to that of clinicians who are not specialized in dermatology.

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk

PubMed Central

Hebebrand, Johannes; Holm, Jens-Christian; Woodward, Euan; Baker, Jennifer Lyn; Blaak, Ellen; Schutz, Dominique Durrer; Farpour-Lambert, Nathalie J.; Frühbeck, Gema; Halford, Jason G.C.; Lissner, Lauren; Micic, Dragan; Mullerova, Dana; Roman, Gabriela; Schindler, Karin; Toplak, Hermann; Visscher, Tommy L.S.; Yumuk, Volkan

2017-01-01

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way. PMID:28738325

Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating*

PubMed Central

Marques, Silvio Alencar

2013-01-01

Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression, paracoccidioidomycosis is an important disease for dermatologists, who must be up-to-date about it. This article focuses on recent epidemiological data and discusses the new insights coming from molecular studies, as well as those related to clinical, diagnostic and therapeutic aspects. In the latter section, we give particular attention to the guideline on paracoccidioidomycosis organized by specialists in this subject. PMID:24173174

[On the issues of functioning of the clinic of research institute of balneology].

PubMed

2012-01-01

The article presents the results of analysis of effectiveness of application of main resources in organizing and quality supporting of medical diagnostic care to patients in the clinic of research institute of balneology profile. The result data points out the insufficient effectiveness of application of these resources; the defects in organization and quality of curative diagnostic and rehabilitation care. They determine the priority directions of enhancement of functioning of the institution being a clinical base of research institute of balneology.

Brain profiling and clinical-neuroscience.

PubMed

Peled, Avi

2006-01-01

The current psychiatric diagnostic system, the diagnostic statistic manual, has recently come under increasing criticism. The major reason for the shortcomings of the current psychiatric diagnosis is the lack of a scientific brain-related etiological knowledge about mental disorders. The advancement toward such knowledge is further hampered by the lack of a theoretical framework or "language" that translates clinical findings of mental disorders to brain disturbances and insufficiencies. Here such a theoretical construct is proposed based on insights from neuroscience and neural-computation models. Correlates between clinical manifestations and presumed neuronal network disturbances are proposed in the form of a practical diagnostic system titled "Brain Profiling". Three dimensions make-up brain profiling, "neural complexity disorders", "neuronal resilience insufficiency", and "context-sensitive processing decline". The first dimension relates to disturbances occurring to fast neuronal activations in the millisecond range, it incorporates connectivity and hierarchical imbalances appertaining typically to psychotic and schizophrenic clinical manifestations. The second dimension relates to disturbances that alter slower changes namely long-term synaptic modulations, and incorporates disturbances to optimization and constraint satisfactions within relevant neuronal circuitry. Finally, the level of internal representations related to personality disorders is presented by a "context-sensitive process decline" as the third dimension. For practical use of brain profiling diagnosis a consensual list of psychiatric clinical manifestations provides a "diagnostic input vector", clinical findings are coded 1 for "detection" and 0 for "non-detection", 0.5 is coded for "questionable". The entries are clustered according to their presumed neuronal dynamic relationships and coefficients determine their relevance to the specific related brain disturbance. Relevant equations calculate and normalize the different values attributed to relevant brain disturbances culminating in a three-digit estimation representing the three diagnostic dimensions. brain profiling has the promise for a future brain-related diagnosis. It offers testable predictions about the etiology of mental disorders because being brain-related it lends readily to brain imaging investigations. Being presented also as a one-point representation in a three-dimensional space, multiple follow-up diagnoses trace a trajectory representing an easy-to-see clinical history of the patient. Additional, more immediate, advantages involve reduced stigma because it relaters the disorder to the brain not the person, in addition the three-digit diagnostic code is clinically informative unlike the DSM codes that have no clinical relevance. To conclude, brain profiling diagnosis of mental disorders could be a bold new step toward a "clinical-neuroscience" substituting "psychiatry".

Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial.

PubMed

Brenner, Thorsten; Decker, Sebastian O; Grumaz, Silke; Stevens, Philip; Bruckner, Thomas; Schmoch, Thomas; Pletz, Mathias W; Bracht, Hendrik; Hofer, Stefan; Marx, Gernot; Weigand, Markus A; Sohn, Kai

2018-02-01

Sepsis remains a major challenge, even in modern intensive care medicine. The identification of the causative pathogen is crucial for an early optimization of the antimicrobial treatment regime. In this context, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care, although they are associated with relevant limitations. Accordingly, culture-independent molecular diagnostic procedures might be of help for the identification of the causative pathogen in infected patients. The concept of an unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) has recently been identified to be a promising diagnostic platform for critically ill patients suffering from bloodstream infections. Although this new approach might be more sensitive and specific than culture-based state-of-the-art technologies, additional clinical trials are needed to exactly define the performance as well as clinical value of a NGS-based approach. Next GeneSiS is a prospective, observational, noninterventional, multicenter study to assess the diagnostic performance of a NGS-based approach for the detection of relevant infecting organisms in patients with suspected or proven sepsis [according to recent sepsis definitions (sepsis-3)] by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard (culture-based) microbiological diagnostics. The clinical value of this NGS-based approach will be estimated by a panel of independent clinical specialists, retrospectively identifying potential changes in patients' management based on NGS results. Further subgroup analyses will focus on the clinical value especially for patients suffering from a failure of empiric treatment within the first 3 days after onset [as assessed by death of the patient or lack of improvement of the patient's clinical condition (in terms of an inadequate decrease of SOFA-score) or persistent high procalcitonin levels]. This prospective, observational, noninterventional, multicenter study for the first time investigates the performance as well as the clinical value of a NGS-based approach for the detection of bacteremia in patients with sepsis and may therefore be a pivotal step toward the clinical use of NGS in this indication. DRKS-ID: DRKS00011911 (registered October 9, 2017) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011911; ClinicalTrials.gov Identifier: NCT03356249 (registered November 29, 2017) https://clinicaltrials.gov/ct2/show/NCT03356249.

Shoulder pain in primary care: diagnostic accuracy of clinical examination tests for non-traumatic acromioclavicular joint pain

PubMed Central

2013-01-01

Background Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. Methods Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics. Following a standardised clinical examination and diagnostic injection into the subacromial bursa, all participants received a fluoroscopically guided diagnostic block of 1% lidocaine hydrochloride (XylocaineTM) into the ACJ. Diagnostic accuracy statistics including sensitivity, specificity, predictive values, positive and negative likelihood ratios (LR+ and LR-) were calculated for traditional ACJ tests (Active Compression/O’Brien’s test, cross-body adduction, localised ACJ tenderness and Hawkins-Kennedy test), and for individual and combinations of clinical examination variables that were associated with a positive anaesthetic response (PAR) (P≤0.05) defined as 80% or more reduction in post-injection pain intensity during provocative clinical tests. Results Twenty two of 153 participants (14%) reported an 80% PAR. None of the traditional ACJ tests were associated with an 80% PAR (P<0.05) and combinations of traditional tests were not able to discriminate between a PAR and a negative anaesthetic response (AUC 0.507; 95% CI: 0.366, 0.647; P>0.05). Five clinical examination variables (repetitive mechanism of pain onset, no referred pain below the elbow, thickened or swollen ACJ, no symptom provocation during passive glenohumeral abduction and external rotation) were associated with an 80% PAR (P<0.05) and demonstrated an ability to accurately discriminate between an PAR and NAR (AUC 0.791; 95% CI 0.702, 0.880; P<0.001). Less than two positive clinical features resulted in 96% sensitivity (95% CI 0.78, 0.99) and a LR- 0.09 (95% CI 0.02, 0.41) and four positive clinical features resulted in 95% specificity (95% CI 0.90, 0.98) and a LR+ of 4.98 (95% CI 1.69, 13.84). Conclusions In this cohort of primary care patients with predominantly subacute or chronic ACJ pain of non-traumatic onset, traditional ACJ tests were of limited diagnostic value. Combinations of other history and physical examination findings were able to more accurately identify injection-confirmed ACJ pain in this cohort. PMID:23634871

Routine Ultrasound and Limited Computed Tomography for the Diagnosis of Acute Appendicitis

PubMed Central

Wiersma, Fraukje; Bakker, Rutger F. R.; Merkus, Jos W. S.; Breslau, Paul J.; Hamming, Jaap F.

2010-01-01

Background Acute appendicitis continues to be a challenging diagnosis. Preoperative radiological imaging using ultrasound (US) or computed tomography (CT) has gained popularity as it may offer a more accurate diagnosis than classic clinical evaluation. The optimal implementation of these diagnostic modalities has yet to be established. The aim of the present study was to investigate a diagnostic pathway that uses routine US, limited CT, and clinical re-evaluation for patients with acute appendicitis. Methods A prospective analysis was performed of all patients presenting with acute abdominal pain at the emergency department from June 2005 until July 2006 using a structured diagnosis and management flowchart. Daily practice was mimicked, while ensuring a valid assessment of clinical and radiological diagnostic accuracies and the effect they had on patient management. Results A total of 802 patients were included in this analysis. Additional radiological imaging was performed in 96.3% of patients with suspected appendicitis (n = 164). Use of CT was kept to a minimum (17.9%), with a US:CT ratio of approximately 6:1. Positive and negative predictive values for the clinical diagnosis of appendicitis were 63 and 98%, respectively; for US 94 and 97%, respectively; and for CT 100 and 100%, respectively. The negative appendicitis rate was 3.3%, the perforation rate was 23.5%, and the missed perforated appendicitis rate was 3.4%. No (diagnostic) laparoscopies were performed. Conclusions A diagnostic pathway using routine US, limited CT, and clinical re-evaluation for patients with acute abdominal pain can provide excellent results for the diagnosis and treatment of appendicitis. PMID:20582544

[Detection of rubella virus RNA in clinical material by real time polymerase chain reaction method].

PubMed

Domonova, É A; Shipulina, O Iu; Kuevda, D A; Larichev, V F; Safonova, A P; Burchik, M A; Butenko, A M; Shipulin, G A

2012-01-01

Development of a reagent kit for detection of rubella virus RNA in clinical material by PCR-RT. During development and determination of analytical specificity and sensitivity DNA and RNA of 33 different microorganisms including 4 rubella strains were used. Comparison of analytical sensitivity of virological and molecular-biological methods was performed by using rubella virus strains Wistar RA 27/3, M-33, "Orlov", Judith. Evaluation of diagnostic informativity of rubella virus RNAisolation in various clinical material by PCR-RT method was performed in comparison with determination of virus specific serum antibodies by enzyme immunoassay. A reagent kit for the detection of rubella virus RNA in clinical material by PCR-RT was developed. Analytical specificity was 100%, analytical sensitivity - 400 virus RNA copies per ml. Analytical sensitivity of the developed technique exceeds analytical sensitivity of the Vero E6 cell culture infection method in studies of rubella virus strains Wistar RA 27/3 and "Orlov" by 11g and 31g, and for M-33 and Judith strains is analogous. Diagnostic specificity is 100%. Diagnostic specificity for testing samples obtained within 5 days of rash onset: for peripheral blood sera - 20.9%, saliva - 92.5%, nasopharyngeal swabs - 70.1%, saliva and nasopharyngeal swabs - 97%. Positive and negative predictive values of the results were shown depending on the type of clinical material tested. Application of reagent kit will allow to increase rubella diagnostics effectiveness at the early stages of infectious process development, timely and qualitatively perform differential diagnostics of exanthema diseases, support tactics of anti-epidemic regime.

Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

PubMed

Harrington, Jennifer; Palmert, Mark R

2012-09-01

Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

Proposed Diagnostic Criteria for Smartphone Addiction

PubMed Central

Lin, Yu-Hsuan; Chiang, Chih-Lin; Lin, Po-Hsien; Chang, Li-Ren; Ko, Chih-Hung; Lee, Yang-Han

2016-01-01

Background Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria. Methods We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist’s structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists’ clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy. Results Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use. Conclusion The diagnostic criteria of smartphone addiction demonstrated the core symptoms “impaired control” paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment. PMID:27846211

Proposed Diagnostic Criteria for Smartphone Addiction.

PubMed

Lin, Yu-Hsuan; Chiang, Chih-Lin; Lin, Po-Hsien; Chang, Li-Ren; Ko, Chih-Hung; Lee, Yang-Han; Lin, Sheng-Hsuan

2016-01-01

Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria. We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist's structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists' clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy. Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use. The diagnostic criteria of smartphone addiction demonstrated the core symptoms "impaired control" paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment.

Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

PubMed

Novotny, A; Xiang, J; Stummer, W; Teuscher, N S; Smith, D E; Keep, R F

2000-07-01

5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[(3)H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na(+)-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an alpha-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na(+) and HCO(3)(-) dependent and appears to be an organic anion transporter, although it is possible that removal of Na(+) and HCO(3)(-) may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na(+)/HCO(3)(-)-dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

PubMed Central

Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

2014-01-01

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

Dual-wavelength excitation to reduce background fluorescence for fluorescence spectroscopic quantitation of erythrocyte zinc protoporphyrin-IX and protoporphyrin-IX from whole blood and oral mucosa

NASA Astrophysics Data System (ADS)

Hennig, Georg; Vogeser, Michael; Holdt, Lesca M.; Homann, Christian; Großmann, Michael; Stepp, Herbert; Gruber, Christian; Erdogan, Ilknur; Hasmüller, Stephan; Hasbargen, Uwe; Brittenham, Gary M.

2014-02-01

Erythrocyte zinc protoporphyrin-IX (ZnPP) and protoporphyrin-IX (PPIX) accumulate in a variety of disorders that restrict or disrupt the biosynthesis of heme, including iron deficiency and various porphyrias. We describe a reagent-free spectroscopic method based on dual-wavelength excitation that can measure simultaneously both ZnPP and PPIX fluorescence from unwashed whole blood while virtually eliminating background fluorescence. We further aim to quantify ZnPP and PPIX non-invasively from the intact oral mucosa using dual-wavelength excitation to reduce the strong tissue background fluorescence while retaining the faint porphyrin fluorescence signal originating from erythrocytes. Fluorescence spectroscopic measurements were made on 35 diluted EDTA blood samples using a custom front-face fluorometer. The difference spectrum between fluorescence at 425 nm and 407 nm excitation effectively eliminated background autofluorescence while retaining the characteristic porphyrin peaks. These peaks were evaluated quantitatively and the results compared to a reference HPLC-kit method. A modified instrument using a single 1000 μm fiber for light delivery and detection was used to record fluorescence spectra from oral mucosa. For blood measurements, the ZnPP and PPIX fluorescence intensities from the difference spectra correlated well with the reference method (ZnPP: Spearman's rho rs = 0.943, p < 0.0001; PPIX: rs = 0.959, p < 0.0001). In difference spectra from oral mucosa, background fluorescence was reduced significantly, while porphyrin signals remained observable. The dual-wavelength excitation method evaluates quantitatively the ZnPP/heme and PPIX/heme ratios from unwashed whole blood, simplifying clinical laboratory measurements. The difference technique reduces the background fluorescence from measurements on oral mucosa, allowing for future non-invasive quantitation of erythrocyte ZnPP and PPIX.

[Angina pectoris and coronary insufficiency with a normal coronary angiogram: pathophysiological principles, diagnosis and therapeutic consequences].

PubMed

Strauer, B E

1988-01-01

The clinical syndrome "coronary insufficience at normal coronary arteriogram" is found in approximately 10-20% of patients with exercise-induced coronary insufficience. In most of these cases disturbances of coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis, etc.), in rheological diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia, etc.), and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia, hyperlipoproteinemia). The clinical diagnosis is based on usual diagnostic programs (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin, etc.), as well as on newer, functionally orientated diagnostic procedures (determinations of coronary blood flow and of coronary vascular reserve, production of lactate, serological findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood, etc.). Many clinically relevant disturbances in coronary microcirculation can thus be detected and treated on a rational basis by the management of the internal main disease, that is, by the treatment of the vascular, rheological, and metabolic disorders. Persistent angina pectoris in the presence of normal coronary arteriogram represents no termination of coronary diagnostics, but moreover implies the clinical task for using diagnostic possibilities to enable functional and therapeutical assessment of coronary microcirculation.

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

PubMed Central

Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

2014-01-01

SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

76 FR 27331 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Characteristics of In Vitro Diagnostic Devices for Chlamydia Trachomatis and/or Neisseria Gonorrhoeae: Screening... entitled ``Establishing the Performance Characteristics of In Vitro Diagnostic Devices for Chlamydia... clinical performance of in vitro diagnostic devices (IVDs) intended for C. trachomatis and/or N...

The role of MRI in musculoskeletal practice: a clinical perspective

PubMed Central

Dean Deyle, Gail

2011-01-01

This clinical perspective presents an overview of current and potential uses for magnetic resonance imaging (MRI) in musculoskeletal practice. Clinical practice guidelines and current evidence for improved outcomes will help providers determine the situations when an MRI is indicated. The advanced competency standard of examination used by physical therapists will be helpful to prevent overuse of musculoskeletal imaging, reduce diagnostic errors, and provide the appropriate clinical context to pathology revealed on MRI. Physical therapists are diagnostically accurate and appropriately conservative in their use of MRI consistent with evidence-based principles of diagnosis and screening. PMID:22851878

Analysis of utilization patterns and associated costs of the breast imaging and diagnostic procedures after screening mammography.

PubMed

Vlahiotis, Anna; Griffin, Brian; Stavros, A Thomas; Margolis, Jay

2018-01-01

Little data exist on real-world patterns and associated costs of downstream breast diagnostic procedures following an abnormal screening mammography or clinical exam. To analyze the utilization patterns in real-world clinical settings for breast imaging and diagnostic procedures, including the frequency and volume of patients and procedures, procedure sequencing, and associated health care expenditures. Using medical claims from 2011 to 2015 MarketScan Commercial and Medicare Databases, adult females with breast imaging/diagnostic procedures (diagnostic mammography, ultrasound, molecular breast imaging, tomosynthesis, magnetic resonance imaging, or biopsy) other than screening mammography were selected. Continuous health plan coverage without breast diagnostic procedures was required for ≥13 months before the first found breast diagnostic procedure (index event), with a 13-month post-index follow-up period. Key outcomes included diagnostic procedure volumes, sequences, and payments. Results reported descriptively were projected to provide US national patient and procedure volumes. The final sample of 875,526 patients was nationally projected to 12,394,432 patients annually receiving 8,732,909 diagnostic mammograms (53.3% of patients), 6,987,399 breast ultrasounds (42.4% of patients), and 1,585,856 biopsies (10.3% of patients). Following initial diagnostic procedures, 49.4% had second procedures, 20.1% followed with third procedures, and 10.0% had a fourth procedure. Mean (SD) costs for diagnostic mammograms of US$349 ($493), ultrasounds US$132 ($134), and biopsies US$1,938 ($2,343) contributed US$3.05 billion, US$0.92 billion, and US$3.07 billion, respectively, to annual diagnostic breast expenditures estimated at US$7.91 billion. The volume and expense of additional breast diagnostic testing, estimated at US$7.91 billion annually, underscores the need for technological improvements in the breast diagnostic landscape.

Clinical Reasoning Education at US Medical Schools: Results from a National Survey of Internal Medicine Clerkship Directors.

PubMed

Rencic, Joseph; Trowbridge, Robert L; Fagan, Mark; Szauter, Karen; Durning, Steven

2017-11-01

Recent reports, including the Institute of Medicine's Improving Diagnosis in Health Care, highlight the pervasiveness and underappreciated harm of diagnostic error, and recommend enhancing health care professional education in diagnostic reasoning. However, little is known about clinical reasoning curricula at US medical schools. To describe clinical reasoning curricula at US medical schools and to determine the attitudes of internal medicine clerkship directors toward teaching of clinical reasoning. Cross-sectional multicenter study. US institutional members of the Clerkship Directors in Internal Medicine (CDIM). Examined responses to a survey that was emailed in May 2015 to CDIM institutional representatives, who reported on their medical school's clinical reasoning curriculum. The response rate was 74% (91/123). Most respondents reported that a structured curriculum in clinical reasoning should be taught in all phases of medical education, including the preclinical years (64/85; 75%), clinical clerkships (76/87; 87%), and the fourth year (75/88; 85%), and that more curricular time should be devoted to the topic. Respondents indicated that most students enter the clerkship with only poor (25/85; 29%) to fair (47/85; 55%) knowledge of key clinical reasoning concepts. Most institutions (52/91; 57%) surveyed lacked sessions dedicated to these topics. Lack of curricular time (59/67, 88%) and faculty expertise in teaching these concepts (53/76, 69%) were identified as barriers. Internal medicine clerkship directors believe that clinical reasoning should be taught throughout the 4 years of medical school, with the greatest emphasis in the clinical years. However, only a minority reported having teaching sessions devoted to clinical reasoning, citing a lack of curricular time and faculty expertise as the largest barriers. Our findings suggest that additional institutional and national resources should be dedicated to developing clinical reasoning curricula to improve diagnostic accuracy and reduce diagnostic error.

Evidence base and future research directions in the management of low back pain.

PubMed

Abbott, Allan

2016-03-18

Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care.

Clinical profiles and outcomes in idiopathic duct-centric chronic pancreatitis (type 2 autoimmune pancreatitis): the Mayo Clinic experience.

PubMed

Hart, Phil A; Levy, Michael J; Smyrk, Thomas C; Takahashi, Naoki; Abu Dayyeh, Barham K; Clain, Jonathan E; Gleeson, Ferga C; Pearson, Randall K; Petersen, Bret T; Topazian, Mark D; Vege, Santhi S; Zhang, Lizhi; Chari, Suresh T

2016-10-01

Idiopathic duct-centric chronic pancreatitis (IDCP), also known as type 2 autoimmune pancreatitis (AIP), is an uncommon subtype of AIP. International Consensus Diagnostic Criteria for IDCP propose that the diagnosis requires pancreatic histology and/or concurrent IBD. We examined our experience with IDCP (type 2 AIP) to assess the appropriateness of these criteria, and identify unique characteristics in patients presenting with acute pancreatitis. We reviewed the Mayo Clinic AIP database through May 2014 to identify subjects with either definitive (n=31) or probable (n=12) IDCP. We compared demographic and clinical factors based on strength of diagnostic confidence (definitive versus probable), presence of IBD, and acute pancreatitis as the presenting manifestation. Relapse-free survival was determined using the Kaplan-Meier method. The clinical profiles were similar irrespective of the diagnostic criteria fulfilled. Common clinical presentations included acute pancreatitis (n=25, 58.1%, 12 of whom (27.9%) had recurrent pancreatitis) and pancreatic mass/obstructive jaundice (n=15, 34.9%). The cumulative relapse rate was 10.6% at 3 years (median follow-up 2.9 years). Relapse-free survival was similar for the different diagnostic categories, but was decreased in those initially presenting with acute pancreatitis (p=0.047) or treated with steroids (vs surgery, p=0.049). The current diagnostic classification of probable IDCP and the inclusion of IBD as a supportive criterion appear valid, because patients have similar clinical profiles and disease-related outcomes to those with definitive IDCP. Concurrent IBD, especially in young patients, may suggest when IDCP is the underlying cause of recurrent acute pancreatitis, but additional studies are needed for validation. 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/

Initiating an undiagnosed diseases program in the Western Australian public health system.

PubMed

Baynam, Gareth; Broley, Stephanie; Bauskis, Alicia; Pachter, Nicholas; McKenzie, Fiona; Townshend, Sharron; Slee, Jennie; Kiraly-Borri, Cathy; Vasudevan, Anand; Hawkins, Anne; Schofield, Lyn; Helmholz, Petra; Palmer, Richard; Kung, Stefanie; Walker, Caroline E; Molster, Caron; Lewis, Barry; Mina, Kym; Beilby, John; Pathak, Gargi; Poulton, Cathryn; Groza, Tudor; Zankl, Andreas; Roscioli, Tony; Dinger, Marcel E; Mattick, John S; Gahl, William; Groft, Stephen; Tifft, Cynthia; Taruscio, Domenica; Lasko, Paul; Kosaki, Kenjiro; Wilhelm, Helene; Melegh, Bela; Carapetis, Jonathan; Jana, Sayanta; Chaney, Gervase; Johns, Allison; Owen, Peter Wynn; Daly, Frank; Weeramanthri, Tarun; Dawkins, Hugh; Goldblatt, Jack

2017-05-03

New approaches are required to address the needs of complex undiagnosed diseases patients. These approaches include clinical genomic diagnostic pipelines, utilizing intra- and multi-disciplinary platforms, as well as specialty-specific genomic clinics. Both are advancing diagnostic rates. However, complementary cross-disciplinary approaches are also critical to address those patients with multisystem disorders who traverse the bounds of multiple specialties and remain undiagnosed despite existing intra-specialty and genomic-focused approaches. The diagnostic possibilities of undiagnosed diseases include genetic and non-genetic conditions. The focus on genetic diseases addresses some of these disorders, however a cross-disciplinary approach is needed that also simultaneously addresses other disorder types. Herein, we describe the initiation and summary outcomes of a public health system approach for complex undiagnosed patients - the Undiagnosed Diseases Program-Western Australia (UDP-WA). Briefly the UDP-WA is: i) one of a complementary suite of approaches that is being delivered within health service, and with community engagement, to address the needs of those with severe undiagnosed diseases; ii) delivered within a public health system to support equitable access to health care, including for those from remote and regional areas; iii) providing diagnoses and improved patient care; iv) delivering a platform for in-service and real time genomic and phenomic education for clinicians that traverses a diverse range of specialties; v) retaining and recapturing clinical expertise; vi) supporting the education of junior and more senior medical staff; vii) designed to integrate with clinical translational research; and viii) is supporting greater connectedness for patients, families and medical staff. The UDP-WA has been initiated in the public health system to complement existing clinical genomic approaches; it has been targeted to those with a specific diagnostic need, and initiated by redirecting existing clinical and financial resources. The UDP-WA supports the provision of equitable and sustainable diagnostics and simultaneously supports capacity building in clinical care and translational research, for those with undiagnosed, typically rare, conditions.

Chronic pancreatitis: A diagnostic dilemma

PubMed Central

Duggan, Sinead N; Ní Chonchubhair, Hazel M; Lawal, Oladapo; O’Connor, Donal B; Conlon, Kevin C

2016-01-01

Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland. PMID:26900292

SFEMG in ocular myasthenia gravis diagnosis.

PubMed

Padua, L; Stalberg, E; LoMonaco, M; Evoli, A; Batocchi, A; Tonali, P

2000-07-01

In typical cases, the patient's history and clinical examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in many cases a clear clinical picture is not present and OMG diagnosis is very difficult because gold diagnostic standard tests are not available. The diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. In this paper, we studied 86 cases submitted for suspected OMG. The patients were studied clinically and with various other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti AChR titration, tensilon test). SFEMG showed the highest sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To our knowledge this is the largest population of suspected OMG studied using most of the diagnostic parameters, reported in the literature.

Primary progressive aphasia: a clinical approach.

PubMed

Marshall, Charles R; Hardy, Chris J D; Volkmer, Anna; Russell, Lucy L; Bond, Rebecca L; Fletcher, Phillip D; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Rossor, Martin N; Fox, Nick C; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

2018-06-01

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

Selective Immunophenotyping for Diagnosis of B-cell Neoplasms: Immunohistochemistry and Flow Cytometry Strategies and Results

PubMed Central

Boyd, Scott D.; Natkunam, Yasodha; Allen, John R.; Warnke, Roger A.

2012-01-01

Determining the immunophenotype of hematologic malignancies is now an indispensible part of diagnostic classification, and can help to guide therapy, or to predict clinical outcome. Diagnostic workup should be guided by morphologic findings and evaluate clinically important markers, but ideally should avoid the use of overly-broad panels of immunostains that can reveal incidental findings of uncertain significance and give rise to increased costs. Here, we outline our approach to diagnosis of B cell neoplasms, combining histologic and clinical data with tailored panels of immunophenotyping reagents, in the context of the 2008 World Health Organization classification. We present data from cases seen at our institution from 2004-8 using this approach, to provide a practical reference for findings seen in daily diagnostic practice. PMID:22820658

Location of core diagnostic information across various sequences in brain MRI and implications for efficiency of MRI scanner utilization.

PubMed

Sharma, Aseem; Chatterjee, Arindam; Goyal, Manu; Parsons, Matthew S; Bartel, Seth

2015-04-01

Targeting redundancy within MRI can improve its cost-effective utilization. We sought to quantify potential redundancy in our brain MRI protocols. In this retrospective review, we aggregated 207 consecutive adults who underwent brain MRI and reviewed their medical records to document clinical indication, core diagnostic information provided by MRI, and its clinical impact. Contributory imaging abnormalities constituted positive core diagnostic information whereas absence of imaging abnormalities constituted negative core diagnostic information. The senior author selected core sequences deemed sufficient for extraction of core diagnostic information. For validating core sequences selection, four readers assessed the relative ease of extracting core diagnostic information from the core sequences. Potential redundancy was calculated by comparing the average number of core sequences to the average number of sequences obtained. Scanning had been performed using 9.4±2.8 sequences over 37.3±12.3 minutes. Core diagnostic information was deemed extractable from 2.1±1.1 core sequences, with an assumed scanning time of 8.6±4.8 minutes, reflecting a potential redundancy of 74.5%±19.1%. Potential redundancy was least in scans obtained for treatment planning (14.9%±25.7%) and highest in scans obtained for follow-up of benign diseases (81.4%±12.6%). In 97.4% of cases, all four readers considered core diagnostic information to be either easily extractable from core sequences or the ease to be equivalent to that from the entire study. With only one MRI lacking clinical impact (0.48%), overutilization did not seem to contribute to potential redundancy. High potential redundancy that can be targeted for more efficient scanner utilization exists in brain MRI protocols.

Comparison of Established Diagnostic Methodologies and a Novel Bacterial smpB Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections.

PubMed

Reddington, Kate; Schwenk, Stefan; Tuite, Nina; Platt, Gareth; Davar, Danesh; Coughlan, Helena; Personne, Yoann; Gant, Vanya; Enne, Virve I; Zumla, Alimuddin; Barry, Thomas

2015-09-01

Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzae in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpB gene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilus spp. Subsequently, 44 Haemophilus clinical isolates were collected, and 36 isolates were identified as H. influenzae using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and a fucK diagnostic assay. Using the novel smpB diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n = 98) were blindly tested with the gold standard and smpB diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpB assay when used directly on respiratory specimens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparison of Established Diagnostic Methodologies and a Novel Bacterial smpB Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections

PubMed Central

Reddington, Kate; Schwenk, Stefan; Tuite, Nina; Platt, Gareth; Davar, Danesh; Coughlan, Helena; Personne, Yoann; Gant, Vanya; Enne, Virve I.; Zumla, Alimuddin

2015-01-01

Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzae in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpB gene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilus spp. Subsequently, 44 Haemophilus clinical isolates were collected, and 36 isolates were identified as H. influenzae using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and a fucK diagnostic assay. Using the novel smpB diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n = 98) were blindly tested with the gold standard and smpB diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpB assay when used directly on respiratory specimens. PMID:26109443

Practical perspectives of personalized healthcare in oncology.

PubMed

Hodgson, Darren R; Wellings, Robert; Harbron, Christopher

2012-09-15

There is an increasing prevalence of drug-diagnostic combinations in oncology. This has placed diagnostic stakeholders directly into the complex benefit-risk, cost, value and uncertainty-driven development paradigm traditionally the preserve of the drug development community. In this review we focus on the delivery of the clinical data required to advance such drug-diagnostic combination development programmes and ultimately satisfy regulators and payors of the value of contemporaneous changes in diagnostic and treatment practice. Ideally all stakeholders would like to initially estimate, and ultimately specify, the comparative benefit-risk for a new treatment option with and without changing diagnostic practice. Hence, in an ideal world clinical trial design is focused on acquiring biomarker treatment interaction data. In this review we describe the key scientific and feasibility inputs required to design and deliver such trials and the drivers, advantages and disadvantages associated with departing from this model. We do not discuss the discovery of new biomarkers nor the analytical validation and marketing of diagnostic products. Following on from trial design we describe how subsequent success then depends upon the concepts that guide trial design being driven into the complex world of large, multinational clinical trial delivery. For every aspect of a traditional clinical drug trial such as supply, recruitment and adherence, there is a corresponding concept for the diagnostic element. In practice, this means that each patient's contribution to the decision making data-set is subject to double jeopardy (attrition on clinical outcome and biomarker status). Historically, this has led to significantly reduced power for detecting biomarker-treatment interactions, reduced decision making confidence and a waste of valuable human and financial resources. We describe recent practice changes and experience that have led to the successful delivery of such trials focusing on both pre- and on trial aspects. The former includes the pivotal role of tissue banks in accurate estimation of evaluability and prevalence for biomarker assays and the latter several practices designed to engage and incentivize key stakeholders particularly CRAs and pathologists. The result is that in the new world of developing personalized treatments for cancer patients the real-time acquisition and monitoring of biomarker data receives similar support to that traditionally reserved for clinical outcome data and far more patients contribute to the testing of personalized medicine hypotheses. Copyright © 2012 Elsevier B.V. All rights reserved.

Diagnosis of TIA (DOT) score--design and validation of a new clinical diagnostic tool for transient ischaemic attack.

PubMed

Dutta, Dipankar

2016-02-09

The diagnosis of Transient Ischaemic Attack (TIA) can be difficult and 50-60% of patients seen in TIA clinics turn out to be mimics. Many of these mimics have high ABCD2 scores and fill urgent TIA clinic slots inappropriately. A TIA diagnostic tool may help non-specialists make the diagnosis with greater accuracy and improve TIA clinic triage. The only available diagnostic score (Dawson et al) is limited in scope and not widely used. The Diagnosis of TIA (DOT) Score is a new and internally validated web and mobile app based diagnostic tool which encompasses both brain and retinal TIA. The score was derived retrospectively from a single centre TIA clinic database using stepwise logistic regression by backwards elimination to find the best model. An optimum cutpoint was obtained for the score. The derivation and validation cohorts were separate samples drawn from the years 2010/12 and 2013 respectively. Receiver Operating Characteristic (ROC) curves and area under the curve (AUC) were calculated and the diagnostic accuracy of DOT was compared to the Dawson score. A web and smartphone calculator were designed subsequently. The derivation cohort had 879 patients and the validation cohort 525. The final model had seventeen predictors and had an AUC of 0.91 (95% CI: 0.89-0.93). When tested on the validation cohort, the AUC for DOTS was 0.89 (0.86-0.92) while that of the Dawson score was 0.77 (0.73-0.81). The sensitivity and specificity of the DOT score were 89% (CI: 84%-93%) and 76% (70%-81%) respectively while those of the Dawson score were 83% (78%-88%) and 51% (45%-57%). Other diagnostic accuracy measures (DOT vs. Dawson) include positive predictive values (75% vs. 58%), negative predictive values (89% vs. 79%), positive likelihood ratios (3.67 vs. 1.70) and negative likelihood ratios (0.15 vs. 0.32). The DOT score shows promise as a diagnostic tool for TIA and requires independent external validation before it can be widely used. It could potentially improve the triage of patients assessed for suspected TIA.

Clinical bacteriology in low-resource settings: today's solutions.

PubMed

Ombelet, Sien; Ronat, Jean-Baptiste; Walsh, Timothy; Yansouni, Cedric P; Cox, Janneke; Vlieghe, Erika; Martiny, Delphine; Semret, Makeda; Vandenberg, Olivier; Jacobs, Jan

2018-03-05

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Probability scores and diagnostic algorithms in pulmonary embolism: are they followed in clinical practice?

PubMed

Sanjuán, Pilar; Rodríguez-Núñez, Nuria; Rábade, Carlos; Lama, Adriana; Ferreiro, Lucía; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Toubes, María Elena; Golpe, Antonio; Valdés, Luis

2014-05-01

Clinical probability scores (CPS) determine the pre-test probability of pulmonary embolism (PE) and assess the need for the tests required in these patients. Our objective is to investigate if PE is diagnosed according to clinical practice guidelines. Retrospective study of clinically suspected PE in the emergency department between January 2010 and December 2012. A D-dimer value ≥ 500 ng/ml was considered positive. PE was diagnosed on the basis of the multislice computed tomography angiography and, to a lesser extent, with other imaging techniques. The CPS used was the revised Geneva scoring system. There was 3,924 cases of suspected PE (56% female). Diagnosis was determined in 360 patients (9.2%) and the incidence was 30.6 cases per 100,000 inhabitants/year. Sensitivity and the negative predictive value of the D-dimer test were 98.7% and 99.2% respectively. CPS was calculated in only 24 cases (0.6%) and diagnostic algorithms were not followed in 2,125 patients (54.2%): in 682 (17.4%) because clinical probability could not be estimated and in 482 (37.6%), 852 (46.4%) and 109 (87.9%) with low, intermediate and high clinical probability, respectively, because the diagnostic algorithms for these probabilities were not applied. CPS are rarely calculated in the diagnosis of PE and the diagnostic algorithm is rarely used in clinical practice. This may result in procedures with potential significant side effects being unnecessarily performed or to a high risk of underdiagnosis. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.