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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]

Fluorescent analysis of bone provides valuable insights into bone structures. However, conventional dyes suffer from low specificity on bone tissue, small stokes shift, short fluorescent lifetime, and aggregation‐caused quenching effect, which result in low efficacy and artifacts. In this work, we design an aggregation‐induced emission (AIE)‐active iridium(III) complex (Ir‐BP2) as a highly selective, convenient, nondestructiveness, and dual‐mode staining agent for bone analysis. Ir‐BP2 containing phosphonate groups selectively binds to hydroxyapatites, the main component of bone matrix, and exhibits turn‐on AIE phosphorescence with prolonged lifetime. Ir‐BP2 exhibits promising biosafety and offers higher accuracy in staining calcium deposits than conventional Alizarin Red S staining assay when it is employed in real‐time monitoring of osteogenesis differentiation process. A ready‐to‐use staining spray of Ir‐BP2 is fabricated. By using fluorescent imaging and lifetime imaging, Ir‐BP2 staining provides valuable insights into bone microstructure analysis, microdamage diagnosis, and bone growth state identification. Further, Ir‐BP2 is successfully applied on a human spine vertebra for diagnosing bone invasiveness of eosinophilic granuloma, validating its clinical practice. This work presents a powerful tool in bone analysis and will lead to new approaches for the diagnosis and treatment of bone‐related diseases. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent cancerous tumor in women, characterized by different subtypes and varying responses to treatment. The continued evolution of breast cancer diagnosis and management has resulted in a transition from a one‐size‐fits‐all approach to a new era of personalized treatment plans. Therefore, it is essential to accurately identify the biological characteristics of breast tissue in order to minimize unnecessary biopsies of benign lesions and improve the overall clinical process, leading to reduced expenses and complications associated with invasive biopsy procedures. Challenges for future research include finding ways to predict the response of breast cancer patients to adjuvant systemic treatment. Dual‐energy CT (DECT) is a new imaging technology integrating functional imaging and molecular imaging. Over the past decade, DECT has gained relevancy, especially in oncological radiology. This article proposed a literature review of the application and research status of DECT in breast cancer treatment strategy determination and prognosis prediction. [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]

Although whole‐exome sequencing and whole‐genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA‐seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA‐seq data can be used to identify aberrantly spliced genes, detect allele‐specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA‐seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA‐seq has been implemented to aid in identifying the causal variants of Mendelian disorders. [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]

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]

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: 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 Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ ( t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.

ABSTRACT To determine the proportion of incident radiographic vertebral fractures (vfx) also diagnosed as incident clinical vfx in older men and vice-versa, we used data from 4398 community-dwelling men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study. Incident radiographic vfx were identified by comparing baseline and follow-up lateral thoracic and lumbar spine study films (average 4.6 years between films) using a semiquantitative (SQ) method and defined as a change in SQ reading of ≥1 at a given vertebral level from baseline to follow-up study radiograph. Participants were contacted triannually to ascertain incident clinical vfx; community spinal imaging studies were obtained and clinical vfx were confirmed when the study radiologist determined that the community imaging study showed a new deformity of higher grade than was present in the same vertebra on the baseline study radiograph. A total of 237 incident radiographic vfx were identified in 197 men, whereas 31 men experienced 37 confirmed incident clinical vfx. Of incident radiographic vfx, 13.5% were also clinically diagnosed as incident fractures, with clinical diagnoses made for 16.3% of the radiographic vfx with SQ grade change ≥2. Of incident clinical vfx, 86.5% were identified as incident radiographic vfx, most of them with SQ grade change ≥2. In summary, less than 15% of incident radiographic vfx were also clinically diagnosed, whereas the majority of incident clinical vfx were identified as severe radiographic vfx. These results in men supplement those previously published for women and suggest a complex relationship between clinical and radiographic vfx in older adults. Published 2016.† American Society for Bone and Mineral Research. [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]

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]

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]

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]

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]

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]

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]

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]

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]

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 define the bacteriological and histological correlates of the three predominant clinical forms of cutaneous tuberculosis and to evaluate the efficacy of a 9-month daily regimen containing rifampicin and isoniazid. Methods In the dermatological clinics of two major teaching hospitals in Chennai, 213 patients with suspected clinical manifestations of cutaneous tuberculosis underwent examination and a skin biopsy for bacteriological and histological tests. They were treated with a daily regimen of rifampicin and isoniazid for 9 months and follow-up for 3 years. Results Bacteriological and/or histological confirmation of tuberculosis was obtained in 88% of the cases. Lupus vulgaris lesions were seen mainly in the extremities and verrucosa cutis occurred predominantly on the sole and foot, while the cervical and axillary regions were the commonest sites for scrofuloderma. Ninety-two per cent of the patients showed resolution of the lesions within the first 6 months of chemotherapy; 1% failed to respond to this regimen. There was no relapse in any of the cases during the follow-up period of 3 years. Conclusions Clinical findings were adequate to identify major forms of cutaneous tuberculosis as evidenced by bacteriological and histopathological examination. A daily regimen of rifampicin and isoniazid for 9 months was effective in treating cutaneous tuberculosis. [ABSTRACT FROM AUTHOR]

Objectives To describe the characteristics of patients consulting commune primary healthcare posts for acute undifferentiated fever not being malaria (AUF), and to explore the diagnostic and therapeutic responses of the healthcare workers. Methods All patients presenting with AUF at 12 commune health posts and one clinic at the provincial malaria station, Binh Thuan, a dengue endemic province in southern Vietnam, were included. Record forms were used to fill in patient and diseases characteristics, pre-referral treatment, signs and symptoms, provisional diagnosis and installed treatment, referral and final outcome. Results Two thousand ninety-six patients were included from April 2001 to March 2002. The median delay to attend the health posts was, 0.87 day for >5, 1.15 days for children aged 5–15 years and 1.41 days for adults ( P < 0.001). Sixty-five per cent of patients took some measures before consulting the health post, of whom 82% applied self-medication and 69% took antibiotics. Pre-referral medication with antibiotics increased with age (RR 1.012 per year of age; 95% CI: 1.004–1.019). The diagnostic and therapeutic response of healthcare workers was very unspecific. The tourniquet test was inappropriately used as general discriminating test, not only for detecting dengue haemorrhagic fever. Empiric antibiotic therapy was installed in 77.2% of cases. Conclusions Management of uncomplicated fever, not being malaria, at the primary healthcare level in Vietnam is non-specific, dominated by searching signs of hemorrhagic dengue and empiric antibiotic treatment. This can probably be improved by better education. [ABSTRACT FROM AUTHOR]

We conducted a study of 1945 children and 2885 adults who presented with fever to a hospital outpatients clinic in an urban area of India order to develop and evaluate a clinical algorithm for the diagnosis of malaria. Only 139 (7%) children and 349 (12%) adults had microscopically confirmed malaria. None of the symptoms or signs elicited from the respondents were good predictors of clinical malaria. Simple scores were derived through combining clinical features which were associated with slide positivity or were judged by clinicians to be important. The best-performing algorithms were a score of 4 clinical features in children (sensitivity 60.0% and specificity 61.2%) and a score of 5 in adults (sensitivity 54.6% and specificity 57.5%). The clinical features differed and algorithm performances were poorer than in previous studies in highly endemic areas. The conclusion is that malaria diagnosis in areas of low endemicity requires microscopy to be accurate. [ABSTRACT FROM AUTHOR]

Key Clinical Message If no improvement is seen with ongoing treatment for current diagnosis, then diagnosis should be questioned. History taking and physical examination remain essential tools in care of the patient in addition to the current technological advancement. [ABSTRACT FROM AUTHOR]