215 research outputs found
Optic nerve head and fibre layer imaging for diagnosing glaucoma
Background
The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma.
Objectives
To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage.
Search methods
We searched several databases for this review. The most recent searches were on 19 February 2015.
Selection criteria
We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or
Data collection and analysis
We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level.
Main results
We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear.
Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study. The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio.
Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people.
Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD >=-6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR).
Authors' conclusions
The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base.
We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data
Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation
OBJECTIVES: To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. DESIGN: Systematic review of current evidence and economic modelling. DATA SOURCES: Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered. RESULTS: 26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p </= 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were pound7324 with standard care and pound7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have approximately 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of pound20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not. CONCLUSIONS: Self-monitoring appears to be a safe and cost-effective option. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013004944
mycosis fungoides in childhood description and study of two siblings
Primary cutaneous T-cell lymphomas are exceedingly rare in children and adolescents. However, mycosis fungoides (MF) is the most frequent primary cutaneous lymphoma diagnosed in childhood. Two cases of MF in siblings (a 14-year-old boy and his 10-year-old sister) are reported. On the basis of clinical features (histopathological and immunophenotypical findings) a diagnosis of MF patch lesions was made in both siblings. Since recent data in the literature have underlined a high frequency of the HLA-DQB1*03 allele in patients with familial MF (including child patients), the HLA profile of the patients was analysed, indicating the presence of a haplotype (HLA-DQB1*03,*03 in the girl, HLA-DQB1*02,*03 in the boy) corresponding with that described in recent literature. Two rare and exceptional cases of MF in siblings are reported, highlighting the presence of a peculiar haplotype
La terapia fotodinamica: indicazioni e controindicazioni. Esperienza della Clinica Dermatologica
La terapia fotodinamica (PDT) eÌ una forma di trattamento non chirurgico applicabile a diversi tipi di tumori non cutanei (tumori gastrointestinali, cerebrali, broncopolmonari, endometriali e vescicali) e ad alcuni tumori e lesioni pretumorali della cute. Il principio su cui si basa la PDT eÌ quello di una reazione fotodinamica in grado di distruggere selettivamente le cellule tumorali, ovvero un processo chimico mediato dalla luce (processo foto-chimico) che prevede lâassorbimento della luce da parte di una sostanza fotosensibile e la successiva formazione di specie reattive dellâossigeno (ROS), in grado di distruggere la cellula nella quale si sono formati. Dalla fine degli anni â90 la PDT cutanea eÌ divenuta una valida opzione terapeutica per il dermatologo, e dopo il 2000 eÌ entrata a far parte delle linee guida internazionali per il trattamento dei tumori cutanei non melanocitari (NMSC) quali la cheratosi attinica (AK), il carcinoma basocellulare superficiale (BCC), e recentemente anche il morbo di Bowen (BD).
La tollerabilitaÌ e i vantaggi per il paziente in confronto alle altre terapie ablative chirurgiche e non chirurgiche sono notevoli. La selettivitaÌ per le cellule malate con risparmio del tessuto sano permette di avere una guarigione della lesione ulcerativa post-trattamento piuÌ rapida, di mantenere la funzione della cute, e di ottenere un risultato esteticamente molto piuÌ accettabile. Questi vantaggi sono particolarmente evidenti per le lesioni di ampie dimensioni o per lesioni multiple soprattutto al volto. Inoltre eÌ utile per il trattamento di pazienti anziani o in scadenti condizioni generali o in terapia anticoagulante.
In questo lavoro, presentiamo lâesperienza della Clinica Dermatologica della Fondazione IRCCS Policlinico San Matteo di Pavia a distanza di circa un anno dallâintroduzione della PDT per la terapia dei tumori cutanei non melanocitari: sono stati trattati 29 pazienti e, tenendo conto che alcuni soggetti presentavano piuÌ di una lesione e che in uno stesso paziente potevano essere contemporaneamente presenti lesioni di natura diversa (BD, BCC e/o AK), sono stati nel complesso trattati 4 BD, 21 BCC e 52 AK.
Lâesperienza della Clinica Dermatologica conferma i dati riportati in letteratura sullâefficacia e i vantaggi di que-sto tipo di terapia: i risultati ottenuti sono piuÌ che soddisfacenti con una remissione clinica delle lesioni trattate maggiore del 90% del totale delle lesioni. Gli eventi collaterali sono stati scarsi e caratterizzati da dolore o bru-ciore localizzato allâarea trattata e da aumento della pressione arteriosa durante la procedura.
In conclusione, la PDT si eÌ rivelata una terapia efficace, noncheÌ una valida alternativa nel trattamento dei NMSC
Studies to inform the methods for Cochrane systematic reviews of diagnostic accuracy in stroke medicine
Background
A variety of tests are used in clinical practice to help the diagnostic process and so
improve patient care. Many aspects of stroke management depend on accurate and
rapid diagnosis. Brain imaging, including CT or MRI, is necessary to identify the
location and extent of the cerebral lesion, and to determine the pathological type of
stroke and its likely cause. Current treatments - such as thrombolysis - for ischaemic
stroke have increased the need for clear evidence on which imaging test is optimal
for diagnosis in the acute phase of stroke.
Systematic reviews of diagnostic test accuracy may provide evidence on the best use
of a diagnostic test in clinical practice and help clinicians to decide among alternative
tests. The Cochrane Collaboration has recently included systematic reviews of
diagnostic test accuracy within its remit. However, to prepare Cochrane systematic
reviews of diagnostic test accuracy is challenging because the methods for such
reviews are still in a state of flux.
Materials and methods
The research work undertaken for this thesis addresses four relevant methodological
aspects of such reviews and, I hope, will contribute to informing the development of
the methods for Cochrane systematic reviews of test accuracy:
i) I assessed the quality of reporting of imaging studies in stroke medicine
published between 1995 and 2008 with the current STAndards for the
Reporting of Diagnostic accuracy studies (STARD) criteria;
ii) I assessed the magnitude of publication bias in diagnostic accuracy
studies in stroke medicine, by reviewing all diagnostic abstracts presented
at two international stroke meetings between 1995 and 2004 and so
evaluating the characteristics and findings of the identified abstracts;
iii) I have evaluated the methods for preparing reviews of test accuracy by
undertaking a pilot review according to the draft recommendations of the
Cochrane Diagnostic Test Accuracy Working Group;
iv) I conducted a survey to assess a) how well clinicians and health
professionals interpret findings of Cochrane systematic reviews of
diagnostic accuracy presented in summary documents; and b) what is the
best format for summarising findings of Cochrane reviews of diagnostic
accuracy.
Conclusions
In conclusion, methodological issues concerning the validity and reliability of
findings of studies included in systematic reviews of diagnostic accuracy remain of
fundamental importance. More empirical evidence is needed to address potential
biases such as reporting bias and publication bias. To allow dissemination of
diagnostic reviews findings in clinical practice better ways of communicating main
characteristics and key results of systematic reviews of diagnostic accuracy should be
considered. In the current literature, the quality of reporting and methodological quality of
imaging studies for the diagnosis of stroke is less than satisfactory and leaves room
for improvement. This is worrying, especially if current health imaging policies are
in fact based on poor quality evidence and hence scarce health resources may not
being deployed as effectively as they could be
Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications
Background: âResidual skin surface componentsâ (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of ânormalâ RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatographyâatmospheric pressure chemical ionisationâmass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio
Ciclosporina-A e week-end therapy nella psoriasi a placche: la nostra esperienza
Lâefficacia della Ciclosporina-A (CsA) nel trattamento della psoriasi eÌ nota da 30 anni. La sua maggiore limitazione eÌ peroÌ correlata al rischio di eventi avversi quali lâipertensione arteriosa e lâalterazione della funzionalitaÌ renale che sembrerebbero non solo dose-dipendenti ma anche proporzionali alla durata della terapia. Pertanto, la possibilitaÌ di formulare uno schema di trattamento in grado di controllare efficacemente le manifestazioni cliniche nel lungo termine con un profilo di sicurezza accettabile risulta sempre piuÌ importante al fine di migliorare la qualitaÌ della vita dei pazienti affetti da psoriasi.
Scopo del nostro studio eÌ la valutazione di una terapia con CsA somministrata solo due giorni alla settimana da protrarre su lunghi periodi per il controllo delle recidive di psoriasi.
Il nostro studio prende spunto dalla week-end therapy che si eÌ dimostrata efficace nel mantenimento della remissione a lungo termine ed eÌ stata ben tollerata da tutti i pazienti considerati
Improving diaper design to address incontinence associated dermatitis
<p>Abstract</p> <p>Background</p> <p>Incontinence associated dermatitis (IAD) is an inflammatory skin disease mainly triggered by prolonged skin contact with urine, feces but also liberal detergent use when cleansing the skin. To minimize the epidermal barrier challenge we optimized the design of adult incontinence briefs. In the fluid absorption area we interposed a special type of acidic, curled-type of cellulose between the top sheet in contact with the skin and the absorption core beneath containing the polyacrylate superabsorber. The intention was to minimize disturbance of the already weak acid mantle of aged skin. We also employed air-permeable side panels to minimize skin occlusion and swelling of the stratum corneum.</p> <p>Methods</p> <p>The surface pH of diapers was measured after repeated wetting with a urine substitute fluid at the level of the top sheet. Occlusive effects and hydration of the stratum corneum were measured after a 4 hour application of different side panel materials by corneometry on human volunteers. Finally, we evaluated skin symptoms in 12 patients with preexisting IAD for 21 days following the institutional switch to the optimized diaper design. Local skin care protocols remained in place unchanged.</p> <p>Results</p> <p>The improved design created a surface pH of 4.6 which was stable even after repeated wetting throughout a 5 hour period. The "standard design" briefs had values of 7.1, which is alkaline compared to the acidic surface of normal skin. Side panels made from non-woven material with an air-permeability of more than 1200 l/m<sup>2</sup>/s avoided excessive hydration of the stratum corneum when compared to the commonly employed air-impermeable plastic films. Resolution of pre-existing IAD skin lesions was noted in 8 out of 12 patients after the switch to the optimized brief design.</p> <p>Conclusions</p> <p>An improved design of adult-type briefs can create an acidic pH on the surface and breathable side panels avoid over-hydration of the stratum corneum and occlusion. This may support the epidermal barrier function and may help to reduce the occurrence of IAD.</p
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