Search

Microfluidic Paper‐based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost‐effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on‐site detection, providing results comparable to expensive and sophisticated large‐scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on‐site real‐time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects. [ABSTRACT FROM AUTHOR]

Background: The intersection of artificial intelligence (AI) with cancer research is increasing, and many of the advances have focused on the analysis of cancer images. Objectives: To describe and synthesize the literature on the diagnostic accuracy of AI in early imaging diagnosis of cervical cancer following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for Scoping Reviews (PRISMA‐ScR). Search Strategy: Arksey and O'Malley methodology was used and PubMed, Scopus, and Google Scholar databases were searched using a combination of English and Spanish keywords. Selection Criteria: Identified titles and abstracts were screened to select original reports and cross‐checked for overlap of cases. Data Collection and Analysis: A descriptive summary was organized by the AI algorithm used, total of images analyzed, data source, clinical comparison criteria, and diagnosis performance. Main Results: We identified 32 studies published between 2009 and 2022. The primary sources of images were digital colposcopy, cervicography, and mobile devices. The machine learning/deep learning (DL) algorithms applied in the articles included support vector machine (SVM), random forest classifier, k‐nearest neighbors, multilayer perceptron, C4.5, Naïve Bayes, AdaBoost, XGboots, conditional random fields, Bayes classifier, convolutional neural network (CNN; and variations), ResNet (several versions), YOLO+EfficientNetB0, and visual geometry group (VGG; several versions). SVM and DL methods (CNN, ResNet, VGG) showed the best diagnostic performances, with an accuracy of over 97%. Conclusion: We concluded that the use of AI for cervical cancer screening has increased over the years, and some results (mainly from DL) are very promising. However, further research is necessary to validate these findings. Synopsis: The role of artificial intelligence in cervical cancer screening has grown, showing promising results, particularly in deep learning. However, further research is required to validate these findings. [ABSTRACT FROM AUTHOR]

Early clinical diagnosis, effective intraoperative guidance, and an accurate prognosis can lead to timely and effective medical treatment. The current conventional clinical methods have several limitations. Therefore, there is a need to develop faster and more reliable clinical detection, treatment, and monitoring methods to enhance their clinical applications. Raman spectroscopy is noninvasive and provides highly specific information about the molecular structure and biochemical composition of analytes in a rapid and accurate manner. It has a wide range of applications in biomedicine, materials, and clinical settings. This review primarily focuses on the application of Raman spectroscopy in clinical medicine. The advantages and limitations of Raman spectroscopy over traditional clinical methods are discussed. In addition, the advantages of combining Raman spectroscopy with machine learning, nanoparticles, and probes are demonstrated, thereby extending its applicability to different clinical phases. Examples of the clinical applications of Raman spectroscopy over the last 3 years are also integrated. Finally, various prospective approaches based on Raman spectroscopy in clinical studies are surveyed, and current challenges are discussed. [ABSTRACT FROM AUTHOR]

We report a case of drug‐induced lung injury treated with prior atezolizumab and subsequent sotorasib. The patient was a 62‐year‐old woman with lung adenocarcinoma harbouring a KRAS G12C mutation that was resistant to chemotherapy, including immune checkpoint inhibitors. Cough and dyspnea appeared on day 80 after sotorasib was administered as second‐line therapy, and chest computed tomography revealed ground glass opacities in all lung lobes. Bronchoalveolar lavage fluid showed an increased total cell count with lymphocyte predominance. The patient was considered to have lung injury caused by prior atezolizumab or sotorasib administration. Withdrawal of sotorasib did not improve symptoms and shadows in both lungs. We administered moderate‐dose prednisolone and the lung disorder quickly resolved. Prednisolone tapering was completed in 2 months, followed by several months without relapse. Definitive identification of the responsible drug for the drug‐induced lung injury proved challenging in the setting of exposure to multiple potential inciting agents. There is a need for high levels of clinical suspicion for timely evaluation and management.We report a case of drug‐induced lung injury treated with prior atezolizumab and subsequent sotorasib. Definitive identification of the responsible drug for the drug‐induced lung injury proved challenging in the setting of exposure to multiple potential inciting agents. There is a need for high levels of clinical suspicion for timely evaluation and management. [ABSTRACT FROM AUTHOR]

Aim: Whether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis. Methods: The presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated. Results: We found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high‐pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139‐1G > C homozygous mutation. Conclusion: These results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2024; 24: 161–167. [ABSTRACT FROM AUTHOR]

Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10–15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single‐cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y‐chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies that is usually detected late in the clinic. The currently available diagnostic tools for CRC are either invasive or insensitive to early lesions due to the dearth of reliable biomarkers. In this study, we discovered that the extracellular vesicles (EVs) in the faeces of CRC patients can act as a potent biomarker for the non‐invasive diagnosis and prognosis of CRC. This finding is based on the identification of two transmembrane proteins—CD147 and A33—on faeces‐derived EVs (fEVs) that are intrinsically associated with CRC. The detection results show that the levels of CD147 and A33 on fEVs were upregulated in the CRC patients (n = 48), dramatically distinguishing them from the healthy donors (n = 16). The CD147/A33‐enriched EVs offer a clinical sensitivity of 89%, much higher than that (40%) of carcinoembryonic antigen (CEA), a clinically‐established serum biomarker for CRC diagnosis. In addition, the analysis of longitudinal faeces samples (n = 29) demonstrated that the CD147/A33‐enriched fEVs can be utilized to track the prognosis of CRC. Due to the high compliance of faeces‐based detection, the CD147/A33‐enriched fEVs could serve as new‐generation CRC biomarkers for large‐scale, non‐invasive CRC screening as well as real‐time monitoring of patient outcomes during clinical interventions. [ABSTRACT FROM AUTHOR]

Background: There is no translation for bloating in Spanish, and distension is very technical. Aims: To evaluate pictograms for assessing bloating/distension in patients with general gastroenterology (Study 1, n = 88) and in those with irritable bowel syndrome [IBS] (Study 2: n = 144), and to correlate them with verbal descriptors (VDs) and physician's diagnosis (PDx). Methods: Patients answered the Rome III Questionnaire with VDs and pictograms, and were consulted by two gastroenterology fellows (PDx). Correlations were conducted with Cohen's kappa, and ROC curves were used to contrast pictograms and VDs with PDx. Results: "Inflammation" was the most frequent VDs, while distension was commonly interpreted as a sensation ("inflammation") and/or increased abdominal girth. In patients not reporting bloating/distension with VDs, pictograms detected these symptoms in (Study 1 and Study 2) 82.2 and 89.6% of patients. In addition, pictograms showed a positive agreement with PDx, kappa: 0.63 (p < 0.0001) and 0.8 (p < 0.0001); and a negative agreement with VD, kappa: −0.45 (p = 0.05) and −0.1 (p = 0.2), respectively, in studies 1 and 2. Pictograms were more sensitive and specific than VDs (Study 1: ROC = 0.90 (95% CI: 0.80–0.96), p < 0.0001 versus 0.74 (0.62–0.88), p < 0.0001; Study 2: 0.99 (0.98–1.00), p = 0.004 versus 0.32 (0.10‐0.54), p = 0.294). Conclusions: Pictograms are more effective than Spanish VDs for bloating/distension in patients consulting for gastroenterology problems and those with IBS, supporting their usefulness in the clinic and research studies. There are no expressions for bloating in languages such as Spanish, and distension is very technical for patients to understand. Generic pictograms detected bloating/distension in more than 82% of patients who did not report them with verbal descriptors, and they were more sensitive and specific than verbal descriptors. [ABSTRACT FROM AUTHOR]

Within the past two decades, the escalation of research output in nanotechnology fields has boosted the development of novel nanoparticles and nanostructured substrates for use as matrices in surface assisted laser desorption/ionization mass spectrometry (SALDI‐MS). The application of nanomaterials as matrices, rather than organic matrices, offers remarkable characteristics that allow the analysis of small molecules with fewer matrix interfering peaks, and share higher detection sensitivity, specificity, and reproducibility. The technological advancement of SALDI‐MS has in turn, propelled the application of the analytical technique in the field of biomedical analysis. In this review, the properties and fabrication methods of nanostructured substrates in SALDI‐MS such as metallic‐, carbon‐, and silicon‐based nanostructures, quantum dots, metal‐organic frameworks, and covalent‐organic frameworks are described. Additionally, the latest progress (most within 5 years) of biomedical applications in small molecule, large biomolecule, and MS imaging analysis including metabolite profiling, drug monitoring, bacteria identification, disease diagnosis, and therapeutic evaluation are demonstrated. Key parameters that govern nanomaterial's SALDI efficiency in biomolecule analysis are also discussed. Finally, perspectives of the future development are given to provide a better advancement and promote practical application in clinical MS. [ABSTRACT FROM AUTHOR]

Background: Female pattern hair loss (FPHL) is a non‐scarring hair disease characterized by progressive hair diminishment and decrease of its density. Although typical cases of FPHL are usually straightforward to diagnose, its initial forms can be unrecognized and often need the use of other diagnostic methods. Objective: To describe the accuracy of a diagnosis of FPHL based on clinical grounds and videodermoscopy compared with scalp biopsy. Methods: An observational diagnostic test study was performed. Scalp biopsies were read by the same dermatopathologist and processed horizontally to allow follicle's number and size evaluation. Digital videodermoscopy was also performed. Results: A total of 202 patients were enrolled, but only 35 women were assessed with digital videodermoscopy. When clinical diagnosis was compared to scalp biopsy, a sensitivity, specificity, positive predictive value (PPV), and a negative predictive value (NPV), of 77% %, 72.4%, 82.2%; and 65.5%, were respectively obtained. Videodermoscopy showed a sensitivity, specificity, PPV and NPV of 88.9%, 100%, 100%, and 72.7%, respectively. Conclusions: This study provided valuable information on the accuracy of clinical examination of FPHL, showed the usefulness of videodermoscopy as a method that in the future may replace scalp biopsy for its diagnosis, or also could aid patient´s follow‐up. [ABSTRACT FROM AUTHOR]

Purpose: To provides the clinical and genetic characteristics of a series of Chinese patients with X‐linked juvenile retinoschisis (XLRS) through multimodal imaging and next‐generation sequencing. Methods: Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed. Results: Twenty‐five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best‐corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X‐linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype–phenotype association was observed. Conclusion: This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype–phenotype correlations were found. [ABSTRACT FROM AUTHOR]

Diagnostic medical imaging plays an imperative role in clinical assessment and treatment of medical abnormalities. The fusion of multimodal medical images merges complementary information present in the multi‐source images and provides a better interpretation with improved diagnostic accuracy. This paper presents a CT–MR neurological image fusion method using an optimised biologically inspired neural network in nonsubsampled shearlet (NSST) domain. NSST decomposed coefficients are utilised to activate the optimised neural model using particle swarm optimisation method and to generate the firing maps. Low and high‐frequency NSST subbands get fused using max‐rule based on firing maps. In the optimisation process, a fitness function is evaluated based on spatial frequency and edge index of the resultant fused image. To analyse the fusion performance, extensive experiments are conducted on the different CT–MR neurological image dataset. Objective performance is evaluated based on different metrics to highlight the clarity, contrast, correlation, visual quality, complementary information, salient information, and edge information present in the fused images. Experimental results show that the proposed method is able to provide better‐fused images and outperforms other existing methods in both visual and quantitative assessments. [ABSTRACT FROM AUTHOR]

Diagnostic medical imaging plays an imperative role in clinical assessment and treatment of medical abnormalities. The fusion of multimodal medical images merges complementary information present in the multi-source images and provides a better interpretation with improved diagnostic accuracy. This paper presents a CT–MR neurological image fusion method using an optimised biologically inspired neural network in nonsubsampled shearlet (NSST) domain. NSST decomposed coefficients are utilised to activate the optimised neural model using particle swarm optimisation method and to generate the firing maps. Low and high-frequency NSST subbands get fused using max-rule based on firing maps. In the optimisation process, a fitness function is evaluated based on spatial frequency and edge index of the resultant fused image. To analyse the fusion performance, extensive experiments are conducted on the different CT–MR neurological image dataset. Objective performance is evaluated based on different metrics to highlight the clarity, contrast, correlation, visual quality, complementary information, salient information, and edge information present in the fused images. Experimental results show that the proposed method is able to provide better-fused images and outperforms other existing methods in both visual and quantitative assessments. [ABSTRACT FROM AUTHOR]

A variety of causative factors of infertility in male dogs has been reported. In this study, the results of clinical examination and semen evaluation of 61 infertile stud dogs are described. Infertility was defined as conception failure of at least three matings with different bitches. The dogs, belonged to various breeds, were 4–8 years old and had a history of prior normal fertility. The dogs were subjected to clinical examination including ultrasonography of the prostate and testes. The semen was evaluated using CASA and microscopically morphology and live‐dead spermatozoa. In all dogs, the semen parameters were outside the reference range, and mostly oligoastheno‐teratozoospermia was found. There were also three cases of azoospermia. Thirty dogs showed no clinical abnormalities of the genital organ and no signs of systemic diseases, and testicular degeneration was assumed as the possible cause of infertility. In 20 dogs, BPH was diagnosed. In three dogs, infertility was associated with hypothyroidism. Three dogs had a history of babesiosis, and one dog prolonged ketoconazole treatment. One case each of chronic prostatitis, prostatic adenocarcinoma, epididymitis and retrograde ejaculation was diagnosed. The cause of acquired infertility could not be identified in almost half of the dogs. In other, infertility was often associated with prostate diseases. [ABSTRACT FROM AUTHOR]

Objective: COVID‐19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS‐CoV‐2 infection in suspected patients reported to the Brazilian surveillance system. Methods: We analysed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who travelled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation. Results: We described 1468 COVID‐19 cases (confirmed by RT‐PCR) and 4271 patients with other illnesses. With a data subset including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41–96.67%) for the diagnosis of COVID‐19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51–97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%). Conclusion: We obtained a model suitable for the clinical diagnosis of COVID‐19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modelling epidemiological trends. [ABSTRACT FROM AUTHOR]

Fitz‐Hugh‐Curtis syndrome should be suspected in sexually active young women presenting with acute right upper quadrant pain even in the absence of lower abdominal pain. The risk of radiation exposure associated with computed tomography should also be considered while making a diagnosis of abdominal pain in young patients. [ABSTRACT FROM AUTHOR]

With the wide applications of biomedical images in the medical field, the segmentation of biomedical images plays an important role in clinical diagnosis, pathological analysis, and medical intervention. Full convolutional neural networks, especially U‐net, have improved the performance of segmentation greatly in recent years. However, due to their regular geometric structure, the standard convolutions that they use are inherently limited in dealing with geometric transformations while biomedical objects have huge variations in shape and size. In this study, the authors propose the DRU‐net, which is a novel U‐net with deformable encoder and reshaping upsampling convolution decoder, for biomedical image segmentation. First, deformable convolutional networks are applied and improved to enhance the learning ability of the encoder for geometric transformations. Second, a novel upsampling method named reshape upsampling convolution is proposed for better‐restoring resolution and fusion features. Furthermore, focal loss is used to address class imbalance and model overwhelmed problems in biomedical image segmentation tasks. Theoretic analysis and experimental results have shown that the proposed algorithm not only reduces the number of parameters of U‐Net, but also achieves produces competitive results compared with the state‐of‐the‐art algorithms in terms of various quantitative measures on Drosophila electron microscopy dataset and Warwick‐QU dataset. [ABSTRACT FROM AUTHOR]

Medical image quality requirements have been increasingly stringent with the recent developments of medical technology. To meet clinical diagnosis needs, an effective medical image enhancement method based on convolutional neural networks (CNNs) and frequency band broadening (FBB) is proposed. Curvelet transform is used to deal with medical data by obtaining the curvelet coefficient in each scale and direction, and the generalised cross‐validation is implemented to select the optimal threshold for performing denoising processing. Meanwhile, the cycle spinning scheme is used to wipe off the visible ringing effects along the edges of medical images. Then, FBB and a new CNN model based on the retinex model are used to improve the processed image resolution. Eventually, pixel‐level fusion is made between two enhanced medical images from CNN and FBB. In the authors' study, 50 groups of medical magnetic resonance imaging, X‐ray, and computed tomography images in total have been studied. The experimental results indicate that the final enhanced image using the proposed method outperforms other methods. The resolution and the edge details of the processed image are significantly enhanced, providing a more effective and accurate basis for medical workers to diagnose diseases. [ABSTRACT FROM AUTHOR]

Background: Appropriate depression care is a cancer‐care priority. However, many cancer survivors live with undiagnosed and untreated depression. Prostate cancer survivors may be particularly vulnerable, but little is known about their access to depression care. The goal of this study was to describe patterns and predictors of clinical diagnosis and treatment of depression in prostate cancer survivors. Methods: Generalized estimating equations were used to evaluate indicators of self‐reported clinical diagnosis and treatment depression as a function of individual‐level characteristics within a longitudinal dataset. The data were from a population‐based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 on the North Carolina‐Louisiana Prostate Cancer Project (N = 1,031), and prospectively followed annually from 2008 to 2011 on the Health Care Access and Prostate Cancer Treatment in North Carolina (N = 805). Results: The average rate of self‐reported clinical diagnosis of depression was 44% (95% CI: 39%‐49%), which declined from 60% to 40% between prostate cancer diagnosis and 5‐7 years later. Factors associated with lower odds of self‐reported clinical diagnosis of depression include African‐American race, employment, age at enrollment, low education, infrequent primary care visits, and living with a prostate cancer diagnosis for more than 2 years. The average rate of self‐reported depression treatment was 62% (95% CI: 55%‐69%). Factors associated with lower odds of self‐reported depression treatment included employment and living with a prostate cancer diagnosis for 2 or more years. Conclusion: Prostate cancer survivors experience barriers when in need of depression care. [ABSTRACT FROM AUTHOR]

Objectives: To examine how misidentification of dementia affects estimation of Medicare costs in a largely minority cohort of participants for whom accurate in‐person diagnoses are available. Design: Prospective cohort study. Setting: Washington Heights‐Inwood Columbia Aging Project, a multiethnic, population‐based, prospective study of cognitive aging of Medicare beneficiaries aged 65 and older. Participants: Individuals clinically diagnosed with dementia (n=495) and individuals clinically diagnosed without dementia (n=1,701). Measurements: Medicare claims‐identified dementia was defined according to the presence of any International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for Alzheimer's disease and related dementias in all available claims during the study period. Participant characteristics associated with claims misidentification of dementia were estimated using logistic regression. Effects of dementia misidentification on Medicare expenditures were estimated using generalized linear models. Results: Medicare claims correctly identified 250 of the 495 (51%) dementia cases and 1,565 of the 1,701 (92%) nondementia cases. Sensitivity of claims‐identified dementia was 0.51, and specificity was 0.92. Average annual Medicare expenditures were $14,721 for a beneficiary with a clinical diagnosis of dementia, and $18,208 for a beneficiary with claim‐identified dementia, suggesting an overestimation of $3,487 per person per year when Medicare claims were used to identify dementia. Total annual expenditures for all beneficiaries with claims‐identified dementia were $258,707 lower than that for all those who were clinically diagnosed, suggesting an overall underestimation of total Medicare expenditures if Medicare claims were used to identify dementia. Different types of misidentification have different effects on dementia‐related cost estimates. Average annual expenditures per person were highest for false positives. Conclusion: Misidentification of dementia in Medicare claims is common. Using claims to identify dementia may result in significantly biased estimates of the cost of dementia. J Am Geriatr Soc 67:269–276, 2019. [ABSTRACT FROM AUTHOR]

Herein, a DNAzyme‐powered nanomachine responsive to multiple hepatocellular carcinoma (HCC)‐related miRNAs derived from clinical samples was designed. Initially, three types of nanomachines were constructed with dye molecule [(fluorescein (FAM), tetramethylrhodamin (TMR), and Cyanine 5 (Cy5)]‐labeled DNA–RNA chimeric substrates and a specific recognized probe for the corresponding miRNAs target. Once the target miRNAs were captured by two recognizing probes, the DNA nanomachine was initiated, leading to the hybridization between the DNAzyme and the substrates. With the help of a cofactor, the automatic operation of the nanomachine was driven by cyclic cleavage of the DNAzyme. Meanwhile, we also explored the recognition behavior between the recognizing probe and the target miRNA. Subsequently, these DNAzyme‐powered nanomachines were developed for the homogeneous and simultaneous detection of three target miRNAs at the femtomloar level. Furthermore, the potential in clinical diagnosis was proven by the successful determination of target miRNA in real clinical samples. Thus, this nanomachine‐based strategy possesses significant potential to be an innovation in miRNA analysis methodology. Come together: The design of a DNAzyme‐driven nanomachine able to respond to a specific microRNA is presented. The potential of this strategy is proven by the successful application on real clinical samples (see figure). [ABSTRACT FROM AUTHOR]

Aiming at the lack of signal preprocessing in current rectal signal research, a new 15th‐order Newton iterative fast independent component analysis (FastICA) algorithm is proposed to separate the signal. To solve the incomplete problem of the single channel rectal pressure signal, C‐C phase space reconstruction technology is used for multi‐dimensional signal reconstruction. In order to achieve the diagnosis of rectal dynamic after artificial anal sphincter implantation, the preprocessed rectal signal component is subjected to short‐time Fourier transforms for time–frequency analysis. This constitutes a complete rectal dynamic function diagnosis process. The non‐stationary simulation signal is constructed to verify the preprocessing method. A complete diagnostic experiment is performed on two rectal signals of different gut dynamic. Simulation results show that the proposed method can realise the preprocessing of non‐stationary signals. Through the rectal dynamic function experiment based FastICA‐STFT, two different rectal signals are distinguished, and the results are consistent with the clinical diagnosis, which has achieved the diagnosis of rectal motility. This study will provide support for the recovery of rectal dynamic function in patients with artificial anal sphincter implants. [ABSTRACT FROM AUTHOR]

Abstract: Rationale, aims, and objectives: In this study, we have attempted to replicate the findings of altered emotional processing in depressed patients compared with healthy controls by means of functional magnetic resonance imaging during passive viewing of positive, negative, and neutral pictures from the International Affective Pictures System. Methods: Nineteen medicated depressed patients and 19 sex and age‐matched healthy controls underwent functional magnetic resonance imaging during presentation of affective pictures in a block design. The differences between the blood oxygen level dependent signal elicited in the tree conditions were compared. Within‐group and between‐group analyses were performed with stringent criteria for statistical inference (P < .05 with family‐wise error correction). Results: In medicated depressed patients, positive pictures compared with neutral pictures activated predominantly the posterior cingulate cortex and precuneus, as well as occipital and middle temporal areas mainly on the left side, while in healthy controls, only the occipito‐temporal areas demonstrated significant activation. The negative pictures elicited stronger activation of occipital and temporal regions in both groups and of inferior frontal gyrus only in control subjects. The difference between the groups did not reach statistical significance. Positive correlation was demonstrated between activation levels of clusters located in left precuneus/posterior cingulate cortex and left inferior/middle occipital gyrus and Montgomery‐Asberg Depression Rating Scale scores in patients while viewing positive compared with neutral pictures. Conclusions: Although the within‐group analysis demonstrated significant activations in both groups with apparent discrepancies, the between‐group analysis did not reach statistical significance under the stringent criteria for statistical inference. These results are further contextualized in the critical debate on the methodological issues of clinical evaluation in psychiatry, more specifically the validity and consistency of the applied methods and the limitations existing in the attempts to provide sound cross‐disciplinary validation of the diagnostic tools by means of neuroscience. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to assess through a questionnaire the features of vertiginous episodes, accompanying symptoms, familial history, and migraine precursors in a sample of 252 subjects with a diagnosis of definite vestibular migraine. Background: Migraine is a common neurological disorder characterized by episodic headaches with specific features. About two‐thirds of cases run in families, and patients may refer symptoms occurring in infancy and childhood, defined as episodic syndromes that may be associated with migraine. Migraine is associated with episodic vertigo, called vestibular migraine, whose diagnosis mainly relies on clinical history showing a temporary association of symptoms. Methods: In this cross‐sectional multicentric study, 252 subjects were recruited in different centers; a senior specialist through a structured questionnaire assessed features of vestibular symptoms and accompanying symptoms. Results: The age of onset of migraine was 23 years, while onset of vertigo was at 38 years. One hundred and eighty‐four subjects reported internal vertigo (73%), while 63 subjects (25%) reported external vertigo. The duration of vertigo attacks was less than 5 minutes in 58 subjects (23%), between 6 and 60 minutes in 55 (21.8%), between 1 and 4 hours in 29 (11.5%), 5 and 24 hours in 44 (17.5%), up to 3 days in 14 (5.5%), and more than 3 days in seven (2.8%); 14 subjects (5.5%) referred attacks lasting from less than 5 minutes and up to 1 hour, nine (3.6%) referred attacks lasting from less than 5 minutes and up to 1 to 4 hours, six (2.4%) referred attacks lasting from less than 5 minutes and up to 5 to 24 hours, and five (2%) cases referred attacks lasting from less than 5 minutes and up to days. Among accompanying symptoms, patients referred the following usually occurring, in order of frequency: nausea (59.9%), photophobia (44.4%), phonophobia (38.9%), vomiting (17.8%), palpitations (11.5%), tinnitus (10.7%), fullness of the ear (8.7%), and hearing loss (4%). In total, 177 subjects referred a positive family history of migraine (70.2%), while 167 (66.3%) reported a positive family history of vertigo. In the sample, 69% of patients referred at least one of the pediatric precursors, in particular, 42.8% of subjects referred motion sickness. The age of onset of the first headache was lower in the subsample with a familial history of migraine than in the total sample. Among the pediatric precursors, benign paroxysmal vertigo – BPV, benign paroxysmal torticollis, and motion sickness were predictive of a lower age of onset of vertigo in adulthood; cyclic vomiting was predictive for vomiting during vertigo attacks in adults. Conclusions: Our results may indicate that vestibular symptoms in pediatric patients may act as a predisposing factor to develop vestibular migraine at an earlier age in adulthood. [ABSTRACT FROM AUTHOR]

Abstract: Doctors occasionally make diagnoses in strangers outside of formal medical settings by using the medical skill of visual inspection, such as noticing signs of melanoma or the symptoms of hyperthyroidism. This may cause considerable moral unease and doubts on the side of the diagnosing physician. Such encounters force physicians to consider whether or not to intervene by introducing themselves to the stranger and offering an unsolicited medical opinion despite the absence of a formal doctor‐patient relationship. A small body of literature has addressed the topic of the unsolicited medical opinion, often with a primary focus on practical advice. This article seeks to establish an ethical‐theoretical basis for physicians' ethical obligation to offer an unsolicited medical opinion when they make a diagnosis by visual inspection in a stranger outside of the formal medical context. Using a utilitarian approach, it is argued that, if it is in the physicians' power to prevent a possible loss of well‐being, without thereby sacrificing anything of equal value, physicians have an ethical obligation to intervene. [ABSTRACT FROM AUTHOR]

Background: Intra-oral photographs have been aided diagnosis of several pathologies in teledentistry. Mobile phone cameras may produce high-quality photographs, presenting itself as a viable tool for remote diagnosis of traumatic dental injuries. Aim: To evaluate the levels of interexaminer agreement in cases of traumatic dental injuries when comparing diagnoses conducted in person and remotely. Material and Methods: The sample included 40 patients with 73 traumatized teeth, and a total of 90 diagnoses, who had presented to two dental clinics, one private, and the other public, in Brazil's Federal District. The dental history and clinical examination data were registered in electronic forms, and digital photographs were captured with a mobile phone camera and uploaded to a cloud drive. Six remote examiners formulated their diagnoses based solely on photographic analysis. Thereafter, they were provided with additional clinical data and asked to provide a second round of diagnoses. These diagnoses were compared to those conducted in person, which were considered the gold standard. The data were analyzed with Gwet's AC1 interexaminers' measure to evaluate the agreement between the in-surgery and remote diagnoses. Results: The levels of interexaminer agreement between the in-surgery and remote diagnoses formulated exclusively with images were 0.83 or higher (95% confidence interval: 0.73-0.91), and 0.93 or higher (95% confidence interval: 0.88-0.97), when clinical information was available. Conclusion: The precision of the remote diagnoses was comparable to the diagnoses conducted in person. The levels of interexaminer agreement were higher when clinical data were included with the images. Mobile phones may be an effective tool for capturing images that assist in the remote diagnosis of traumatic dental injuries. [ABSTRACT FROM AUTHOR]

Aim: Screening children with type 1 diabetes for coeliac disease is controversial, because they often appear asymptomatic. Our aim was to establish whether active screening should be recommended.Methods: This study focused on 22 children whose coeliac disease was detected by serological screening during diabetes surveillance and 498 children diagnosed because of a clinical suspicion. We compared the clinical and histological data at diagnosis and the children's adherence and responses to a gluten-free diet.Results: The serological screening group suffered less from decreased growth (p = 0.016) and clinical symptoms (p < 0.001) at diagnosis than the clinical group. The groups did not differ in terms of age at diagnosis (p = 0.903), gender (p = 0.353), anaemia (p = 0.886), endomysial antibody titres (p = 0.789) and the severity of small-bowel mucosal atrophy (p = 0.104). They also showed equal adherence (p = 0.086) and clinical responses (p = 0.542) to a gluten-free diet after a median follow-up of 13 months.Conclusion: Coeliac patients detected during diabetes surveillance had signs of malabsorption and advanced mucosal damage that was similar to those diagnosed on a clinical basis. They often suffered from unrecognised gluten-dependent symptoms and showed excellent adherence and responses to a gluten-free diet. Our findings support active screening for coeliac disease in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose We aimed to identify a combined prognostic factor for predicting better performance in risk stratification. Materials and Methods We reviewed the clinical and pathological variables of 316 patients with oral squamous cell carcinoma ( OSCC) who underwent surgery. To identify a combined predictor, principal component analysis ( PCA) was performed. Results Univariate analysis showed that the independent prognostic variables for overall survival ( OS) were pathologic T stage (T1 vs T4, HR = 1.99, 95% CI: = 1.083-3.675, P = 0.026) and pathologic N stage (N0 vs N2, HR=1.90, 95% CI: = 1.17-3.08, P = 0.008). In the multivariate analysis, only pathologic T stage was significant ( P = 0.006 and P = 0.007); however, the multivariate model was not significant ( P = 0.191). The multivariate model became significant by including lymph node ratio ( LNR) instead of pathologic N stage ( P = 0.0025 in numeric LNR, P = 0.0007 in categorized LNR). Also, the performance of prediction model was improved by a combined prognostic factor ( P = 0.0002). Conclusions The newly identified combined prognostic factor included resection margin, differentiation, and LNR, and they were insignificant factors independently except for LNR. This combined prognostic factor showed a good performance although it did not include molecular markers; therefore, it may be used conveniently for risk stratification of patients with OSCC by combining only clinical information. [ABSTRACT FROM AUTHOR]

Capillary polymer electrophoresis is identified as a promising technology for the analysis of DNA from bacteria, virus and cell samples. In this paper, we propose an innovative capillary polymer electrophoresis protocol for the quantification of polymerase chain reaction products. The internal standard method was modified and applied to capillary polymer electrophoresis. The precision of our modified internal standard protocol was evaluated by measuring the relative standard deviation of intermediate capillary polymer electrophoresis experiments. Results showed that the relative standard deviation was reduced from 12.4-15.1 to 0.6-2.3%. Linear regression tests were also implemented to validate our protocol. The modified internal standard method showed good linearity and robust properties. Finally, the ease of our method was illustrated by analyzing a real clinical oral sample using a one-run capillary polymer electrophoresis experiment. [ABSTRACT FROM AUTHOR]

Lipidomics is an important branch of metabolomics, which aims at the detailed analysis of lipid species and their multiple roles in the living system. In recent years, the development of various analytical methods for effective identification and characterization of lipids has greatly promoted the process of lipidomics. Meanwhile, as many diseases demonstrate a remarkable alteration in lipid profiles compared with that of healthy people, lipidomics has been extensively introduced to disease research. The comprehensive lipid profiling provides a chance to discover novel biomarkers for specific disease. In addition, it plays a crucial role in the study of lipid metabolism, which could illuminate the pathogenesis of diseases. In this review, after brief discussion of analytical methods for lipidomics in clinical research, we focus on the recent advances of lipidomics related to four types of diseases, including cancer, atherosclerosis, diabetes mellitus, and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism (CHI) has been mostly associated with mutations in seven major genes. We retrospectively reviewed a cohort of 32 patients with CHI. Extensive mutational analysis (ABCC8, KCNJ11, GCK, GLUD1, HADH, HNF4A, and UCP2) was performed on Ion torrent platform, which could analyze hundreds of genes simultaneously with ultrahigh-multiplex PCR using up to 6144 primer pairs in a single primer pool and address time-sensitive samples with single-day assays, from samples to annotated variants, to identify the genetic etiology of this disease. Thirty-seven sequence changes were identified, including in ABCC8/KCNJ11 (n = 25, 65.7%), GCK (n = 2), HNF4A (n = 3), GLUD1 (n = 2), HADH (n = 4), and UCP2 (n = 1); these mutations included 14 disease-causing mutations, eight rare SNPs, 14 common SNPs, and one novel mutation. Mutations were identified in 21 of 32 patients (65.6%). Among the patients with an identified mutation, 14 had mutations in ABCC8, one of which was combined with a GLUD1 mutation. Four patients had mutations in KCNJ11, 1 had a GCK mutation, 1 had a mutation in HADH, and two had a mutation in HNF4A. Among the 32 patients, the age at the onset of hyperinsulinemia ranged from the neonatal period to 1 year of age; five patients underwent a pancreatectomy due to intractable hyperinsulinemia. This study describes novel and previously identified mutations in patients with CHI. The spectrum of mutations in CHI patients represents an important tool for the diagnosis and prognosis of CHI patients in the Chinese population as well as for the genetic counseling of CHI families. [ABSTRACT FROM AUTHOR]

The most widely used clinical technique for estimating bone movements in knee joints with acceptable accuracy utilises implantation of heavy metallic beads into the bones. These small metallic objects become visible as highly contrasting features in captured radiographs, thus facilitating post kinematic assessment of bones in human joints with pinpoint accuracy. Although, this approach provides necessary precision for clinical diagnosis, pre‐ and post‐surgery planning for restoring joint function and locomotion, however, this approach also incurs high degree of invasiveness. In this study, a novel optical sensor is proposed for use in non‐invasive motion measurement of knee joints in three‐dimensional (3D) space. The approach is based on 3D angle‐of‐arrival (AoA) estimation using image processing procedures on the two‐dimensional images of sensor's aperture shadows. The novelty of the sensor in terms of design, operation and its potential applications for a wide range of possibilities including precise AoA estimation for unconstrained 3D motion analysis of knee joints is described. Finally, error analysis of the sensor's AoA measurement uncertainty is provided for different incident angles of optical beams, which demonstrates the potential of the sensor not only for high‐precision motion analysis of human joints; however, for other motion and position‐aware systems. [ABSTRACT FROM AUTHOR]

Background Several risk factors already have been determined for dogs with degenerative mitral valve disease ( DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination ( PE). Hypothesis/Objectives Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification. Animals Client-owned dogs (n = 244) with DMVD recruited from first opinion practice. Methods Prospective longitudinal follow-up of dogs with DMVD. History and PE data were obtained at 6-month intervals and analyzed with time-dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score ( CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken. Results History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes. Conclusions and Clinical Importance Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings. [ABSTRACT FROM AUTHOR]

The high prevalence of non-alcoholic fatty liver disease ( NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver ( NAFL) and non-alcoholic steatohepatitis ( NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/ NASH rests on clinicopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining 'non-alcoholic'; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol. [ABSTRACT FROM AUTHOR]

Tissue classification using computer aided diagnosis can help automated decision making to aid clinical diagnosis. Classification of breast tissue based on spectral features of impedance loci has frequently been done to classify malignant tissue with further requirement of more complex classification methodologies needed to improve the characterisation. In current study, tissue classification is done using in vivo electrical impedance data of 18 human subjects, from four quadrants of breast, palm, nail, arm, bicep and classified using algorithms involving machine learning methodologies, specifically support vector machines (SVMs) that are supervised learning models. They consist of learning algorithms based on the principal of structural risk minimisation. Two methodologies of SVM have been used in this study: with data binning and data pruning and without data binning and data pruning. Data binning and data pruning have improved the sensitivity of the SVM from 76.76 to 89.23%, but the specificity has decreased from 76.23 to 74.15%. This is a pilot study towards testing the reliability of the developed electrical impedance measuring system and developing a data mining‐based decision making system into an electrical impedance spectroscopy system, to help users (physicians) with tissue classification leading to reliable objective decision making. [ABSTRACT FROM AUTHOR]

Introduction: Dysferlin deficiency causes dysferlinopathies. Among peripheral blood mononuclear cells (PBMCs), the dysferlin protein is expressed specifically in CD14+ monocytes. Methods: We quantified dysferlin protein levels in PBMC lysates of 77 individuals suspected clinically of having a dysferlinopathy to screen for true positives. Subsequent molecular confirmation was done by Sanger sequencing and comparative genomic hybridization arrays to establish diagnosis. Results: Of the 44 individuals who had significantly reduced dysferlin levels (⩽10%), 41 underwent molecular testing. We identified at least 1 mutation in 85% (35 of 41), and 2 mutations, establishing a dysferlinopathy diagnosis, in 61% (25 of 41) of these individuals. Among those with dysferlin protein levels of >10% (33 of 77), only 1 individual (of 14 who underwent molecular testing) had a detectable mutation. Conclusions: Our results suggest that dysferlin protein levels of ⩽10% in PBMCs, are highly indicative of primary dysferlinopathies. However, this assay may not distinguish carriers from those with secondary dysferlin reduction. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Dysferlin deficiency causes dysferlinopathies. Among peripheral blood mononuclear cells (PBMCs), the dysferlin protein is expressed specifically in CD14+ monocytes. Methods: We quantified dysferlin protein levels in PBMC lysates of 77 individuals suspected clinically of having a dysferlinopathy to screen for true positives. Subsequent molecular confirmation was done by Sanger sequencing and comparative genomic hybridization arrays to establish diagnosis. Results: Of the 44 individuals who had significantly reduced dysferlin levels (≤10%), 41 underwent molecular testing. We identified at least 1 mutation in 85% (35 of 41), and 2 mutations, establishing a dysferlinopathy diagnosis, in 61% (25 of 41) of these individuals. Among those with dysferlin protein levels of >10% (33 of 77), only 1 individual (of 14 who underwent molecular testing) had a detectable mutation. Conclusions: Our results suggest that dysferlin protein levels of ≤10% in PBMCs, are highly indicative of primary dysferlinopathies. However, this assay may not distinguish carriers from those with secondary dysferlin reduction. Muscle Nerve 50: 333-339, 2014 [ABSTRACT FROM AUTHOR]

Objective Epilepsy care in developing countries is challenged by the paucity of trained specialists, diagnostic tools, and antiepileptic drugs ( AEDs). We retrospectively evaluated how epilepsy was managed in a Nigerian tertiary referral center, with the goals of determining diagnostic accuracy by comparing clinical and electroencephalography ( EEG) diagnoses, the appropriateness of prescribed therapy by clinician specialization, and the association between therapy and patient outcomes. Methods We examined the medical records of 372 patients diagnosed with epilepsy in the center over a 6-month period from 2011 to 2012. Data were obtained on methods of diagnosis, clinician specialization, therapeutic care, and patient self- or caregiver-reported outcome on follow-up visits. Interrater agreement was assessed using Cohen's κ coefficient, and the diagnoses made by nonspecialist and specialist clinicians compared using the chi-square test. Results Of 372 patients diagnosed with epilepsy, only one had a brain computerized tomography ( CT) scan. Seventy-six were differentially diagnosed for generalized or partial epilepsy by both clinical presentation and EEG. Low interrater agreement (κ = 0.05) was found between these methods of diagnosis. Of the 76 patients, 53 (69.7%) received therapies judged as appropriate, with no significant difference in prescription rates for appropriate therapy between nonspecialists and specialists (p = 0.536). Specific syndromic diagnoses were made only in 4% of patients, and only in patients who underwent EEG. Only three first-generation AEDs were prescribed, with 97.6% of patients receiving carbamazepine. Significance The discrepancy between diagnoses made on clinical features alone versus EEG diagnosis suggests that in many patients without concomitant EEG, the epileptic syndrome might have been erroneously classified, with increased risk of inappropriate treatment. Resources should be more properly directed toward increasing access to diagnostic facilities and newer generation AEDs. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a serious chronic condition strongly affecting quality of life, which can be relieved but cannot be cured. Apart from symptomatic management, treatment should focus on the underlying disorder. The estimated prevalence is at least 1% to 5% of the general population. Neuropathic pain is characterized both by spontaneous and evoked pain. A diagnosis of neuropathic pain can usually be established based solely on history and neurological examination. Ancillary investigations may include EMG and computerized tomography/magnetic resonance imaging scans, depending on the localization of the suspected lesion. A limited number of agents, primarily directed at symptom control, are currently approved for use in neuropathic pain. A mechanism-based approach to pharmacological intervention supports the use of polypharmacy in neuropathic pain. [ABSTRACT FROM AUTHOR]

Problem-based learning can be an effective tool to develop clinical reasoning skills. However, it traditionally takes place in tutorial groups, giving students little flexibility in how and when they learn. This pilot study compared the effectiveness of generic reflective feedback ( GRF) with tutorial-based reflective feedback on the development of students' clinical reasoning skills. Case studies were placed in an interactive software package, with GRF for the nine patient cases (36 GRF forms in total). The GRF contained information about common mistakes and omissions made by students in previous years. By design, the GRF left some clinical questions unanswered in order to prompt student reflection, enhance the development of their clinical reasoning skills and give the 2010 students ( n = 53) greater control over the way in which they engaged with the unit. Clinical reasoning skills development, assessed by responses to the 36 parts across the 9 cases and in the relevant section of the final exam, was compared with the 2009 tutorial cohort ( n = 47 students). GRF enabled student progression through each of the nine online cases with minimal tutor intervention. The cohort receiving GRF performed as well as those students engaging in tutorials with individualized feedback. GRF was associated with a significant increase in student satisfaction and flexibility in how and when they learned. We conclude that GRF enabled online enhancement of a case-based clinical reasoning unit. Further research on how GRF can optimize learning in different online settings is warranted. [ABSTRACT FROM AUTHOR]

Diagnosis during the initial stages of first-episode psychosis is particularly challenging but crucial in deciding on treatment. This is compounded by important differences in the two major classification systems, International Classification of Diseases, 10th revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). We aimed to compare the concordance between an operationalized diagnosis using Operational Criteria Checklist (OPCRIT) and treating clinician-generated diagnosis in first-episode psychosis diagnosis and its correlation with treatment prescribed. Operationalized polydiagnostic assessments were conducted on 150 first-episode psychosis patients using OPCRIT. OPCRIT-generated ICD-10, DSM-IV and treating clinician diagnoses were compared. The association between these diagnoses and choice of treatment was evaluated. General agreement between the three classification systems was moderate to good, with kappa values between 0.460 and 0.674. There was a higher frequency of schizophrenia diagnosis in ICD-10 ( n = 85) comparing to DSM-IV ( n = 45) and similar in clinical diagnosis ( n = 76), with moderate to good agreement between classifications (kappa between 0.602 and 0.731). No significant differences were found for ratings of psychotic depressive and manic/bipolar disorders with psychosis, with affective disorders having the higher agreement. Heterogeneous group of 'other disorders' achieved a kappa value from 0.250 (DSM-IV/ICD-10) to 0.566 (DSM-IV/clinical diagnosis). Despite the challenges in first-episode psychosis diagnosis, it is possible to have a good agreement between OPCRIT-generated (DSM-IV and ICD-10) diagnoses and clinician-based diagnoses, although some differences exist. The choice of psychopharmacological treatment prescribed matches well with these operationalized diagnoses. [ABSTRACT FROM AUTHOR]

Objectives In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances. Methods Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure. Results Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/μl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi’s sarcoma were the most common conditions causing misclassification of virological ART failure. Conclusion Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens. [ABSTRACT FROM AUTHOR]

Background and purpose: Overlooking a potential diagnosis of cauda equina syndrome (CES) can result in severe long-term neurologic deficits. There is a growing trend to order urgent magnetic resonance imaging (MRI) scans of the lumbar spine in any patient presenting with signs suspicious for CES. A substantial number of these MRI scans do not show cauda compression. The purpose of this study is to assess whether clinical characteristics can predict MRI-confirmed cauda compression. Methods: We retrospectively studied 58 consecutive cases of suspected CES who presented at our hospital’s emergency room. Results: Eight of 58 patients had cauda compression on MRI. When measured, MRI + CES patients (6) had more than 500 ml urinary retention. Moreover, when these patients had at least two of the following characteristics: bilateral sciatica, subjective urinary retention or rectal incontinence symptoms, MRI was more probable to demonstrate cauda compression with an OR of 48.00, 95% (CI 3.30–697.21), which was also significant ( P of 0.04). The presence of other symptoms or signs alone was not significantly different between both groups. Conclusion: In our series, urinary retention of more than 500 ml alone or in combination with two or more specific clinical characteristics were the most important predictors of MRI confirmed cauda compressions. [ABSTRACT FROM AUTHOR]

We describe three cases in whom identification of a disease-causing mutation in the TSC1 or TSC2 gene preceded the appearance or detection of symptoms sufficient for a clinical diagnosis of tuberous sclerosis complex (TSC). We suggest that genetic testing be given a more prominent role in the evaluation of individuals with a family history of TSC or symptoms suggestive of TSC and propose that diagnostic criteria be revised to include genetic testing. [ABSTRACT FROM AUTHOR]

Background and objective: A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV1 and FVC. Methods: A retrospective study was conducted of 681 patients with normal FEV1/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy. Results: The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; P < 0.0001). Conclusions: The weak agreement between the clinical diagnosis and the PFT interpretation in patients showing concomitant decreases in FEV1 and FVC suggests that other clinical findings should be assessed in addition to PFT. [ABSTRACT FROM AUTHOR]

Objective To assess the quality of healthcare workers’ performance with regard to malaria diagnosis and treatment and to assess patients’ self-medication with chloroquine (CQ) before and after presentation at a health centre. Methods In the rainy season 2004, in five rural dispensaries in Burkina Faso, we observed 1101 general outpatient consultations and re-examined all these patients. CQ whole blood concentrations of confirmed malaria cases were measured before and after treatment. Results The clinical diagnosis based on fever and/or a history of fever had a sensitivity of 75% and a specificity of 41% when compared to confirmed malaria (defined as an axillary temperature of ≥37.5 °C and/or a history of fever and parasites of any density in the blood smear). Few febrile children under 5 years of age were assessed for other diseases than malaria such as pneumonia. No antimalarial was prescribed for 1.3% of patients with the clinical diagnosis malaria and for 24% of confirmed cases, while 2% received an antimalarial drug prescription without the corresponding clinical diagnosis. CQ was overdosed in 22% of the prescriptions. Before and 2 weeks after consultation, 25% and 46% respectively of the patients with confirmed malaria had potentially toxic CQ concentrations. Conclusion As long as artemisinin-based combination therapy remains unavailable or unaffordable for most people in rural areas of Burkina Faso, self-medication with and prescription of CQ are likely to continue despite increasing resistance. Apart from considering more pragmatic first-line regimens for malaria treatment such as the combination of sulfadoxine-pyrimethamine with amodiaquine, more and better training on careful clinical management of febrile children including an appropriate consideration of other illnesses than malaria should be made available in the frame of the IMCI initiative in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of Mycobacterium ulcerans infection is currently accepted as sufficient basis for treating the disease. Inadequate laboratory resources in the highly endemic areas of Africa often limit possibilities for in-country confirmation of clinical judgement. We analysed records of 99 Buruli ulcer (BU) patients diagnosed clinically and treated surgically at Amasaman Health Centre in Ghana, for whom post-treatment diagnostic laboratory tests were performed. Comparison of clinical diagnoses with test results obtained by an in-country laboratory on samples of excised tissue showed a high specificity of clinical judgement. Among lesions with three laboratory tests (microscopy for acid fast bacilli, culture and IS2404 polymerase chain reaction) done, 94% tested positive at least once and 83% twice. Thus correct clinical diagnosis of BU by well trained health workers is achievable, although the quality of clinical diagnosis should be monitored by intermittent testing in national reference laboratories. However, being retrospective, this study did not permit sensitivity and negative predictive value analysis. [ABSTRACT FROM AUTHOR]

Objective To test the accuracy of clinical symptoms and signs for anaemia in pregnant women, as assessed by nurse-midwives, in two locations in Northern Tanzania. Methods One location was at 1000 m above sea level, the other at 1800 m. Midwives performed examinations and conducted structured interviews to detect severe anaemia at the first antenatal care visit before haemoglobin (hb) results were revealed; 369 and 535 women of all parities were examined in consecutive order at the two locations. Severe anaemia was defined as hb <75 g/l in the first and <80 g/l in the second (higher) location, based on altitude effect on hb distributions. Results Hb distribution differed substantially between the two locations, with much higher hb levels among those living at 1800 m. Sensitivities for detection of severe anaemia based on individual signs (pallor, conjunctiva, etc.) were 0.85, but only 0.33 to 0.44 for those living at lower and for those at higher altitudes, respectively. Conversely, specificities were around 0.90 at higher and 0.55 at lower altitudes, respectively. Symptoms (headache, dizziness, palpitations, etc.) were too common among those without anaemia to be useful as distinguishing features. Changing the definition of severe anaemia to higher cut-off hb values did not materially alter the results. Conclusion Validity of non-invasive tests to detect severe anaemia in pregnant women varies by locality. In a high-altitude area detection rate was low (sensitivity around 40%). In lower-lying areas detection rate was high, at the cost of low specificity (around 45% false positive tests). Symptoms like headache, dizziness and fatigue were too common to discriminate those with severe anaemia. [ABSTRACT FROM AUTHOR]

While preterm contractions occur almost as often extremely preterm as they do closer to term, birth due to spontaneous preterm labour before 27 weeks of gestation is rare, accounting for 0.05–0.7% of all births in different populations. Although the likelihood that uterine contractions before 27 weeks of gestation represent true preterm labour is low, the risk of adverse outcome in such cases is high. A correct diagnosis is important, and a useful diagnostic test should have a high sensitivity. In most reports, only 30–40% of women hospitalised for spontaneous preterm labour experience a preterm birth, suggesting a low positive predictive value of clinical diagnosis based on uterine contractions and vaginal examination. Transvaginal ultrasonographic scanning (TVUSS) of cervical length has shown a high sensitivity for preterm birth, 90–100% for preterm birth before 33–35 weeks, using a liberal cutoff at 30 mm. Assessment of cervicovaginal fetal fibronectin (FFN) levels has shown a sensitivity of about 80%. Adding FFN assessment to TVUSS might contribute insignificantly to the prediction of preterm birth. In a retrospective study of 147 women with spontaneous preterm labour and intact membranes before 27 weeks in our department, 61% of hospitalised women and 77% of women receiving tocolytic infusion therapy delivered before 32 weeks. Among 66 singleton pregnancies delivered before 32 weeks, at admission, 94% either had an effaced cervix or cervix with ≥2 cm dilation (74%), vaginal bleeding (61%) or serum C-reactive protein level >20 mg/l (40%), whereas one of these findings only was present in 18% of women who delivered at later gestations. Among 132 women with symptoms of spontaneous preterm contractions before 27 weeks not admitted for hospital care, only 2 (1.5%) delivered before 32 weeks, not significantly higher than for all other women (0.6%). Although TVUSS may be useful when the diagnosis of spontaneous preterm labour is in doubt, the main predicament in early spontaneous preterm labour may not be to predict preterm birth but to prevent it, since many women appear in advanced labour or with manifest chorioamnionitis. [ABSTRACT FROM AUTHOR]