Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

8 p.

Impacto da campanha de vacinação para influenza em uma empresa

A influenza é uma das doenças respiratórias agudas mais prevalentes e importante causa de absenteísmo e presenteísmo. Entretanto, a eficácia vacinal para influenza pode alcançar 80% quando há elevada correspondência entre cepas vacinais e circulantes. Por este motivo, a empresa há anos promove campanha de vacinação, contudo, sem estimar sua efetividade (eficácia na redução da carga da doença) e o impacto econômico (produtividade) para o aprimoramento de sua política de saúde ocupacional. Considerou-se que a efetividade da campanha seria determinada pela eficácia vacinal previamente demonstrada em estudos randomizados, pelo grau de acurácia diagnóstica ou de triagem dos casos, pelo nível de adesão do profissional de saúde ao registro no prontuário e do paciente ao informar a ocorrência dos sintomas e pela cobertura vacinal alcançada. Com os objetivos de avaliar a efetividade e impacto econômico da campanha de vacinação para influenza, optou-se por um desenho estudo observacional de coorte histórico com características de estudo de intervenção baseado em dados históricos da campanha de 2008 e informações individuais sobre a frequência de sintomas respiratórios e absenteísmo, idade, gênero, função (administrativa e operacional) e renda, comorbidades relevantes e tabagismo, obtidas mediante revisão de prontuário dos 12 meses subsequentes, comparadas entre os grupos de vacinados e não-vacinados (qui-quadrado e test t) e analisadas por regressão logística, e estimada a fração prevenível (proporção de episódios potenciais de influenza evitados pela vacinação). Foram analisados os prontuários de 2.425 trabalhadores (1.651 não-vacinados e 754 vacinados) correspondendo à cobertura de 31,1%. A prevalência de influenza observada foi de 10,4% e a vacinação foi efetiva entre os trabalhadores (RR=0,51; IC95% 39-67), quando considerados os sintomas de alta probabilidade de influenza. A fração prevenível foi 0,09 (9 casos evitados a cada 100 trabalhadores vacinados). A campanha de vacinação foi mais efetiva e provocou maior impacto econômico entre os trabalhadores em regime operacional.

Prevalência de doença celíaca em pacientes dispépticos sem diarreia atendidos na Disciplina de Gastroenterologia e Endoscopia Digestiva do Hospital Universitário Pedro Ernesto da UERJ

A Doença Celíaca (DC) é uma doença autoimune que afeta o intestino delgado de indivíduos geneticamente susceptíveis após contato com o glúten. Diversos estudos têm relatado aumento da prevalência ao longo dos anos. Objetivo: Determinar a prevalência de DC em pacientes adultos sem diarreia encaminhados à Disciplina de Gastroenterologia do HUPE da UERJ para serem submetidos a Endoscopia Digestiva Alta (EDA).Comparar os resultados do histopatológico das biópsias duodenais com os resultados sorológicos, utilizando o anticorpo antitransglutaminase tecidual IgA (ATGt IgA). Métodos: Pacientes que foram encaminhados ao nosso serviço para serem submetidos a EDA entre Julho de 2008 e Julho de 2010, com idade entre 18 e 85 anos foram aceitos no estudo. Critérios de exclusão foram cirrose, neoplasias do trato gastrointestinal, HIV, uso de imunossupressores e anticoagulantes, diarreia, hemorragia digestiva e DC. Coleta de sangue para pesquisa do anticorpo ATGt IgA (utilizando KIT ORGENTEC - Alemanha), avaliação endoscópica e exame histopatológico das biópsias de segunda porção duodenal foram feitos para cada paciente. Biópsias foram avaliadas de acordo com o critério de Marsh modificado. Resultados: Trezentos e noventa e nove pacientes consecutivos (112 homens, 287 mulheres), média de idade 49,616,4 anos, variando de 18-85 anos, sem diarreia, foram prospectivamente aceitos. Os sintomas clínicos mais prevalentes foram dor abdominal em 99,5%, pirose em 41,1%, plenitude pós prandial em 30,6%, náuseas e vômitos em 21,3%. Os achados endoscópicos foram: normais em 41,6%, lesões pépticas (esofagite, gastrite, duodenite e úlceras) em 41,6%, hérnia hiatal em 5,5%, pólipos gástricos em 3%, neoplasias em 1,3% e miscelânea em 7%. DC foi endoscopicamente diagnosticada em 13 pacientes (3,3%) com mucosa duodenal exibindo serrilhamento das pregas em 8 (2%), diminuição do pregueado em 2 (0,5%) e mucosa exibindo padrão nodular e mosaico em 3 (0,75%). Os achados histopatológicos de duodeno foram normais em 96,7%, duodenites inespecíficas em 2,7% e 3 pacientes (0,75%) confirmaram DC pelos critérios de Marsh modificado (IIIa, IIIb e IIIc). O anticorpo ATGt IgA foi positivo (>10 U/ml) em 1,3% (5/399). Conclusão: Este estudo mostrou que a prevalência de DC em pacientes dispépticos sem diarreia atendidos na Disciplina de Gastroenterologia e Endoscopia do HUPE/UERJ foi de 0,75% (1:133). A acurácia diagnóstica do anticorpo ATGt IgA é boa para pacientes com Marsh III e achados endoscópicos sugestivos. Nenhum dos pacientes tinha alterações Marsh I ou II. A EDA se mostrou um excelente método de triagem para definir os pacientes com graus mais acentuados de atrofia e que se beneficiariam de biópsia e sorologia para confirmação diagnóstica. Os resultados obtidos neste trabalho não justificam uma triagem rotineira de DC.

Novel equation to determine the hepatic triglyceride concentration in humans by MRI: diagnosis and monitoring of NAFLD in obese patients before and after bariatric surgery

Background: Non-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since NAFLD is usually asymptomatic at diagnosis, new non-invasive approaches are needed to determine the hepatic lipid content in terms of diagnosis, treatment and control of disease progression. Here, we investigated the potential of magnetic resonance imaging (MRI) to quantitate and monitor the hepatic triglyceride concentration in humans. Methods: A prospective study of diagnostic accuracy was conducted among 129 consecutive adult patients (97 obesity and 32 non-obese) to compare multi-echo MRI fat fraction, grade of steatosis estimated by histopathology, and biochemical measurement of hepatic triglyceride concentration (that is, Folch value). Results: MRI fat fraction positively correlates with the grade of steatosis estimated on a 0 to 3 scale by histopathology. However, this correlation value was stronger when MRI fat fraction was linked to the Folch value, resulting in a novel equation to predict the hepatic triglyceride concentration (mg of triglycerides/g of liver tissue = 5.082 + (432.104 * multi-echo MRI fat fraction)). Validation of this formula in 31 additional patients (24 obese and 7 controls) resulted in robust correlation between the measured and estimated Folch values. Multivariate analysis showed that none of the variables investigated improves the Folch prediction capacity of the equation. Obese patients show increased steatosis compared to controls using MRI fat fraction and Folch value. Bariatric surgery improved MRI fat fraction values and the Folch value estimated in obese patients one year after surgery. Conclusions: Multi-echo MRI is an accurate approach to determine the hepatic lipid concentration by using our novel equation, representing an economic non-invasive method to diagnose and monitor steatosis in humans.

Efeito do uso de salbutamol nas propriedades mecânicas do sistema respiratório de indivíduos saudáveis, tabagistas e portadores de doença pulmonar obstrutiva crônica

A doença pulmonar obstrução crônica (DPOC) é caracterizada pela limitação de fluxo parcialmente reversível, classificada por níveis de obstrução pós-broncodilatador. Há várias evidências de que o FEV1 sozinho não é capaz de mostrar a broncodilatação de pacientes com DPOC, mesmo naqueles que apresentam melhora clínica. A técnica de oscilações forçadas (TOF) tem mostrado alta sensibilidade na detecção precoce de alterações mecânicas na DPOC, contudo o efeito broncodilatador na impedância respiratória de pacientes com DPOC ainda não está esclarecido. Objetiva avaliar a utilidade da TOF nos diferentes estágios de obstrução das vias aéreas; (2) avaliar a resposta da impedância respiratória ao salbutamol em indivíduos saudáveis ao exame espirométrico e pacientes com DPOC em diferentes graus de gravidade. Foram avaliados 25 indivíduos saudáveis sem história de tabagismo, 24 tabagistas e 151 pacientes com DPOC classificados em graus I, II, III e IV. Todos os sujeitos foram avaliados pela TOF seguida da espirometria, antes e após o uso do salbutamol spray. As curvas de resistência e reatância demonstraram alteração em todos os estágios de obstrução das vias aéreas após o uso do salbutamol. O grupo de risco apresentou alterações mecânicas semelhantes ao grupo leve (p=ns). Os parâmetros R0, Rm, Csr,din e Z4Hz apresentam desempenho diagnóstico adequado (AUC > 0,85) em todos os estágios de gravidade da doença. Todos os parâmetros de TOF e espirometria apresentaram diminuição após uso do salbutamol. Os indivíduos saudáveis apresentaram uma pequena diminuição comparada aos subgrupos de DPOC. A variação em termos absolutos da ΔZ4Hz e das derivadas da resistência, ΔR0, ΔRm, ΔS, apresentaram variação significativa (p<0,0001, p<0,003; p<0,04; p<0,0002, respectivamente) com o aumento da obstrução brônquica. Nas derivadas da reatância o ΔXm aumentou com a gravidade da doença (p<0,0002). Por outro lado, a ΔCrs,dyn não demonstrou diferença significativa com a gravidade da DPOC. Em termos percentuais os parâmetros da TOF apresentaram variação expressiva em ΔRm% (p<0,02), ΔS% (p<0,02) e ΔXm% (p<0,004) com o aumento da obstrução nas vias aéreas. Por outro lado, ΔR0%, ΔCrs,dyn% e ΔZ4Hz% não variaram entre os estágios da DPOC. A associação entre a broncodilatação nas vias aéreas e a impedância pulmonar foi fraca entre ΔXm vs ΔFVC (r=0,32, p<0,0001) e ΔZ4Hz% vs ΔFEV1% vs ΔFVC% (r=0.28, p<0,0005; r=0,29, p<0,0003, respectivamente). A TOF é útil na avaliação das alterações mecânicas nos diferentes níveis de obstrução das vias aéreas na DPOC. Demonstramos o benefício da medicação broncodilatadora, quantificando a melhora da ventilação através da TOF. A impedância respiratória diminui em todos os estágios da DPOC, o estágio leve melhorou tanto quanto o estágio muito grave. Isto sugere que a medida da impedância pulmonar não é dependente do volume como ocorre na espirometria e que a broncodilatação ocorre em todas as fases da progressão da DPOC.

Acurácia da avaliação doppler velocimétrica da velocidade máxima do pico sistólico da artéria cerebral média na detecção da anemia fetal na doença hemolítica perinatal: uma revisão sistemática

O contexto do estudo é a predição da anemia fetal em gestantes portadoras da doença hemolítica perinatal e tem como objetivo avaliar a acurácia da medida doppler velocimétrica da velocidade máxima do pico sistólico da artéria cerebral média na detecção da anemia fetal na doença hemolítica perinatal. A identificação dos estudos foi realizada com a adoção de bancos de dados gerais (MEDLINE e LILACS) e a partir de referências bibliográficas de outros autores. Os estudos selecionados tinham como critérios serem do tipo observacionais, com gestantes apresentando coombs indireto maior do que 1:8, técnica de insonação do vaso adequada, Vmax-ACM ≥ 1,5MOM, presença obrigatória de comparação com o padrão-ouro (hemoglobina fetal e/ou neonatal), e nível de evidência diagnóstica acima ou igual a 4. Os dados dos estudos selecionados foram alocados em tabelas 2x2 comparando o resultado do teste com o padrão-ouro. A acurácia diagnóstica foi expressa principalmente através da razão de verossimilhança. A revisão incluiu onze estudos, com uma amostra total de 688. Três estudos apresentaram delineamento do tipo prospectivo e nível de evidência diagnóstica categoria 1. A performance do teste em questão apresentou variação razoável. O estudo de Mari et al (2000) foi considerado o de melhor qualidade metodológica, apresentando uma RV(+) de 8,45 e uma RV(-) de 0,02. A medida do doppler da Vmax da ACM como preditor da anemia fetal na doença hemolítica perinatal está consolidada. Porém, alguns pontos precisam ser melhor esclarecidos, como o intervalo ideal dos exames em casos graves e a validade do método em fetos que já foram submetidos a transfusões intra-uterinas.

Smartphone ECG for evaluation of STEMI: Results of the ST LEUIS Pilot Study

© 2015 Elsevier Inc. All rights reserved.Background 12-lead ECG is a critical component of initial evaluation of cardiac ischemia, but has traditionally been limited to large, dedicated equipment in medical care environments. Smartphones provide a potential alternative platform for the extension of ECG to new care settings and to improve timeliness of care. Objective To gain experience with smartphone electrocardiography prior to designing a larger multicenter study evaluating standard 12-lead ECG compared to smartphone ECG. Methods 6 patients for whom the hospital STEMI protocol was activated were evaluated with traditional 12-lead ECG followed immediately by a smartphone ECG using right (VnR) and left (VnL) limb leads for precordial grounding. The AliveCor™ Heart Monitor was utilized for this study. All tracings were taken prior to catheterization or immediately after revascularization while still in the catheterization laboratory. Results The smartphone ECG had excellent correlation with the gold standard 12-lead ECG in all patients. Four out of six tracings were judged to meet STEMI criteria on both modalities as determined by three experienced cardiologists, and in the remaining two, consensus indicated a non-STEMI ECG diagnosis. No significant difference was noted between VnR and VnL. Conclusions Smartphone based electrocardiography is a promising, developing technology intended to increase availability and speed of electrocardiographic evaluation. This study confirmed the potential of a smartphone ECG for evaluation of acute ischemia and the feasibility of studying this technology further to define the diagnostic accuracy, limitations and appropriate use of this new technology.

Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group

The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. METHODS: The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. RESULTS: On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. CONCLUSION: Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias

Preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial:is clinical management by realtime teledermatology possible?

Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2 of the trial aimed to assess its effectiveness as a management tool for dermatological disease. Teledermatology consultations were organized between two health centres and two hospitals in Northern Ireland using low-cost videoconferencing equipment. For 205 patients seen by a dermatologist over the video-link a diagnosis and management plan were recorded. A subsequent face-to-face consultation was arranged on the same day to confirm the diagnosis and treatment regime. A comparison of these management plans revealed that the same plan was recommended in 64% of cases; the teledermatologist was unable to advocate a suitable management plan in 19% of cases; a suboptimal treatment plan was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the teledermatologist suggested an inappropriate treatment plan. These findings indicate that appropriate clinical management was possible in approximately two-thirds of dermatology consultations via the video-link.

Clinical practice with anti-dementia drugs:a revised (second) consensus statement from the British Association for Psychopharmacology

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.

Investigation of the Human Brain Metabolome to Identify Potential Markers for Early Diagnosis and Therapeutic Targets of Alzheimer’s Disease

A study combining high resolution mass spectrometry (liquid chromatography-quadrupole time-of-flight-mass spectrometry, UPLC-QTof-MS) and chemometrics for the analysis of post-mortem brain tissue from subjects with Alzheimer’s disease (AD) (n = 15) and healthy age-matched controls (n = 15) was undertaken. The huge potential of this metabolomics approach for distinguishing AD cases is underlined by the correct prediction of disease status in 94–97% of cases. Predictive power was confirmed in a blind test set of 60 samples, reaching 100% diagnostic accuracy. The approach also indicated compounds significantly altered in concentration following the onset of human AD. Using orthogonal partial least-squares discriminant analysis (OPLS-DA), a multivariate model was created for both modes of acquisition explaining the maximum amount of variation between sample groups (Positive Mode-R2 = 97%; Q2 = 93%; root mean squared error of validation (RMSEV) = 13%; Negative Mode-R2 = 99%; Q2 = 92%; RMSEV = 15%). In brain extracts, 1264 and 1457 ions of interest were detected for the different modes of acquisition (positive and negative, respectively). Incorporation of gender into the model increased predictive accuracy and decreased RMSEV values. High resolution UPLC-QTof-MS has not previously been employed to biochemically profile post-mortem brain tissue, and the novel methods described and validated herein prove its potential for making new discoveries related to the etiology, pathophysiology, and treatment of degenerative brain disorders.

Freehand core biopsy in breast cancer: an accurate predictor of tumour grade following neoadjuvant chemotherapy?

Core biopsy is an increasingly used technique in the pre-operative diagnosis of breast carcinoma, as it provides useful prognostic information with respect to tumour type and grade. Neoadjuvant chemotherapy is being used in the treatment of large and locally advanced breast cancers but little is known regarding the correlation between tumour histology on pre-treatment core biopsy and that in residual tumour following primary chemotherapy and surgery. This study aimed to evaluate the accuracy of core biopsy in predicting these features in patients treated with primary chemotherapy. One hundred and thirty-three patients with carcinoma of the breast diagnosed on clinical, radiological and cytological examination underwent core biopsy, followed by primary chemotherapy (with cyclophosphamide, vincristine, doxorubicin and prednisolone) and surgery. The false-negative rate for pre-treatment core biopsy was 14%, with 91% agreement between the grade demonstrated on core biopsy and that in the residual tumour following completion of chemotherapy. Tumour type in the residual post-chemotherapy tumour was predicted by core biopsy in 84%. This study suggests that pre-treatment core biopsy histology accurately predicts residual tumour histology following primary chemotherapy and surgery in patients with breast cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection

Background: Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. Methods: Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection. Results: The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). Conclusions: The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration:a systematic review and economic evaluation

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.

OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.

DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).

REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.

INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).

COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£44,649; QALYs 10.575; incremental cost-effectiveness ratio £47,768). The least costly strategy had a 46.4% probability of being cost-effective at £30,000 willingness-to-pay threshold.

LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.

CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.