Diagnostic performance of a computer-aided system for tuberculosis screening in two Philippine cities

Background and Objectives@#The Philippines faces challenges in the screening of tuberculosis (TB), one of them being the shortage in the health workforce who are skilled and allowed to screen TB. Deep learning neural networks (DLNNs) have shown potential in the TB screening process utilizing chest radiographs (CXRs). However, local studies on AIbased TB screening are limited. This study evaluated qXR3.0 technology's diagnostic performance for TB screening in Filipino adults aged 15 and older. Specifically, we evaluated the specificity and sensitivity of qXR3.0 compared to radiologists' impressions and determined whether it meets the World Health Organization (WHO) standards.@*Methods@#A prospective cohort design was used to perform a study on comparing screening and diagnostic accuracies of qXR3.0 and two radiologist gradings in accordance with the Standards for Reporting Diagnostic Accuracy (STARD). Subjects from two clinics in Metro Manila which had qXR 3.0 seeking consultation at the time of study were invited to participate to have CXRs and sputum collected. Radiologists' and qXR3.0 readings and impressions were compared with respect to the reference standard Xpert MTB/RiF assay. Diagnostic accuracy measures were calculated. @*Results@#With 82 participants, qXR3.0 demonstrated 100% sensitivity and 72.7% specificity with respect to the reference standard. There was a strong agreement between qXR3.0 and radiologists' readings as exhibited by the 0.7895 (between qXR 3.0 and CXRs read by at least one radiologist), 0.9362 (qXR 3.0 and CXRs read by both radiologists), and 0.9403 (qXR 3.0 and CXRs read as not suggestive of TB by at least one radiologist) concordance indices. @*Conclusions@#qXR3.0 demonstrated high sensitivity to identify presence of TB among patients, and meets the WHO standard of at least 70% specificity for detecting true TB infection. This shows an immense potential for the tool to supplement the shortage of radiologists for TB screening in the country. Future research directions may consider larger sample sizes to confirm these findings and explore the economic value of mainstream adoption of qXR 3.0 for TB screening.

Gastroscopy for dyspepsia: Understanding primary care and gastroenterologist mental models of practice: A cognitive task analysis approach.

Background: Gastroscopy to investigate dyspepsia without alarm symptoms rarely results in clinically actionable findings or sustained health-related quality-of-life improvements among patients aged 18-60 years and is, therefore, not recommended. Despite this, referrals for and performance of gastroscopy among this patient population remain high. The purpose of this study was to understand family physicians' and gastroenterologists' mental models of dyspepsia and the drivers behind referring or performing gastroscopy. Methods: Cognitive task analysis routine critical decision method interviews with family physicians (n = 8) and gastroenterologists (n = 4). Results: Family physicians and gastroenterologists hold rich mental models of dyspepsia that rely on sensemaking; however, gaps in information continuity affect their ability to plan and coordinate patient care. Drivers behind decisions to refer or perform gastroscopy were: eliminating risk for serious pathology, providing reassurance, perceived preference by patients to receive information and reassurance from gastroenterologists, maintaining relationships with patients, and saving costs to the health system. Conclusions: Family physicians refer for dyspepsia when they are seeking support from gastroenterologists, they believe that alternative factors may be impacting the patient's health or view it as a cost-saving measure. Likewise, gastroenterologists perform gastroscopy for dyspepsia when they perceive it as a cost-saving measure, they want to support their primary care colleagues and provide their colleagues and patients with reassurance. An improved degree of communication between speciality and primary care could allow for continuity in the transfer of information about patients and reduce referrals for dyspepsia.

Patterns and predictors of elevated blood pressure and hypertension among primary school children in urban Kenya.

OBJECTIVE: We examined the prevalence of elevated blood pressure (BP) and hypertension among 390 primary school children of different socioeconomic status (SES) in two urban settings in Kenya and explored the association between children's BP status and their sociodemographic characteristics, dietary behaviours and overweight/obesity status. METHODS: Children's BP and anthropometric measurements were taken and parents, with the help of their children, completed questionnaires on the children's dietary behaviours. An average of three BP readings was used to calculate BP percentiles by age, sex and height. BMI-for-age z-scores, waist-circumference-to-height ratio and the sum of skinfold measures were calculated. We utilized prevalence ratio analysis to examine the association between BP and sociodemographic characteristics, dietary behaviours and overweight/obesity. RESULTS: About 9% of the school children had elevated BP and 33% had stage 1 hypertension. Among overweight children, the proportion of children with elevated BP was 1.85-fold greater and the proportion of children with hypertension was 1.83-fold greater compared with children with healthy body weight. Similar patterns of significant associations were seen among obese children, children with central obesity and children with high total skinfold values. The proportion of children with hypertension was 1.42-fold greater among children with high frequency of consumption of chips/crisps compared with children with lower frequency of consumption. CONCLUSION: These results increase our understanding BP patterns and determinants among school children in Kenya and can help inform noncommunicable disease prevention efforts.

Perinatal COVID-19 outcomes: evaluating the strength of current evidence.

Purpose of the Study: Viral respiratory diseases, like those caused by novel strains of influenza and Coronaviridae, have historically disproportionately affected pregnant women and conferred increased risk of adverse perinatal outcomes. Initial reports published from Wuhan, China identified only limited symptoms in pregnant women and no cases of mortality, but more recent reports from other regions of the world have reported contrasting information. The purpose of the study was to evaluate initially published cases of SARS-CoV-2 infection in pregnant women in China and compare them to subsequently published studies from the remainder of the world.Materials and Methods: This review curates 199 maternal published cases of SARS-CoV-2 infection and COVID-19 initially reported in the literature from China and contrasts them to more recent literature reporting clinical findings and outcomes of 729 selected cases from the rest of the world, including the United States.Results: Overall, initial case reports and series from China reported no cases of maternal mortality, which contrasts with subsequent reports from other regions of the world demonstrating significant morbidity and mortality can and does occur in pregnant women infected with SARS-CoV-2.Conclusion: While initial reports suggest limited risks of infection in pregnancy with SARS-CoV-2, subsequent findings have demonstrated pregnant women are at risk for severe morbidity and mortality. Case studies and series that are imperative in the early stages of a pandemic to provide data on a novel pathogen cannot be used to provide generalizable information predicting group risks.

Vaccination rates in cochlear implant patients: a review of paediatric recipients.

OBJECTIVE: This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines and to report the incidence of meningitis in this population after intervention. METHOD: A retrospective review of the vaccination coverage of paediatric patients receiving cochlear implants between 2005 and 2019 was performed. RESULTS: Data were collected on 203 children. Evidence of immunisation against Haemophilus influenza B was documented in 94.1 per cent of this cohort and 21.2 per cent received the seasonal influenza vaccine. The pneumococcal conjugate vaccine was fully administered in 81.8 per cent of children; however, only 16.9 per cent of eligible children had received the pneumococcal polysaccharide vaccine. There was marked improvement in compliance to the pneumococcal conjugate vaccine once it became fully funded for cochlear implant patients. CONCLUSION: Despite established guidelines, the paediatric vaccination rates were less than expected. Work is in progress to address this.

Advanced heart failure and heart transplantation in adult congenital heart disease in the current era.

BACKGROUND: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center. METHODS: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery. RESULTS: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21). CONCLUSION: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.

Estimation of the timing of BAP1 mutation in uveal melanoma progression.

Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 µm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.

Validation of the Newly Proposed World Health Organization Classification System for Conjunctival Melanocytic Intraepithelial Lesions: A Comparison with the C-MIN and PAM Classification Schemes.

PURPOSE: We sought to compare the sensitivity, specificity, accuracy, and interobserver agreement of the two most commonly used classification systems for conjunctival melanocytic intraepithelial lesions with the new World Health Organization (WHO) classification. DESIGN: Retrospective case series and evaluation of classification systems. METHODS: We reviewed the pathology and medical records of all patients who underwent a primary biopsy procedure for conjunctival primary acquired melanosis (PAM) at Wills Eye Hospital between 1974 and 2002 who had ≥36 months of follow-up. Data collected included age, sex, clinical findings, recurrence, and progression to melanoma. Twelve ophthalmic pathologists analyzed scanned hematoxylin and eosin-stained virtual microscopic slides using 3 classification systems: PAM, conjunctival melanocytic intraepithelial neoplasia, and the WHO 4th edition classification of conjunctival melanocytic intraepithelial lesions. Observer agreement, sensitivity, specificity, and diagnostic accuracy of each classification system were assessed. RESULTS: There were 64 patients who underwent 83 primary excisions with cryotherapy for conjunctival PAM who had adequate tissue for histopathologic evaluation. The interobserver agreement in distinction between the low- and high-grade lesions was 76% for PAM, 67% for conjunctival melanocytic intraepithelial neoplasia, and 81% for WHO classification system. Low-grade lesions provided the greatest interpretative challenge with all 3 classification systems. The 3 classification systems had comparable accuracy of 81%-83% in their ability to identify lesions with potential for recurrence. CONCLUSIONS: This study highlights the comparable strengths and limitations of the 3 classification systems for conjunctival melanocytic intraepithelial lesions and suggests that the simplified WHO classification scheme is appropriate for evaluation of these lesions.

Participation of Ghanaian pregnant women in an antimalarial drug trial: willingness, experiences and perceptions.

BACKGROUND: With increasing orientation towards including pregnant women in clinical trials, investigators must conduct culturally acceptable research to aid recruitment and retention. There is limited information on experiences and meanings that pregnant women make of trial participation in Africa. This study reports experiences and perceptions of Ghanaian pregnant women regarding their participation in a clinical trial. METHODS: From October to December 2012, 45 in-depth interviews were conducted among pregnant women and their male partners regarding their experiences and perceptions of clinical trial processes as part of an antimalarial drug safety and efficacy trial in pregnant women in the Ashanti region of Ghana. Analysis was by predetermined themes and inductive analysis. RESULTS: Familiarity with the disease studied in the trial and trust in health workers favoured participation with the latter underlying acceptance of study drugs in the absence of symptoms. Adverse drug events were perceived as intrinsic sickness exhibited on the path to wellness. There were no cultural barriers to blood sampling during home visits but hospital-based sampling was preferred. Home visits were linked to participants having HIV infection. CONCLUSION: This study contributes knowledge on sociocultural matters underpinning pregnant women's decisions regarding trial participation in an era of increasing drug trials involving pregnant women.

Digital morphometry of tumor nuclei correlates to BAP-1 status, monosomy 3, gene expression class and survival in uveal melanoma.

Cytologic features such as the shape and size of tumor cells can predict metastatic death in uveal melanoma and other cancers but suffer from poor reproducibility. In this study, we investigate the interobserver concordance of digital morphometry, and correlate the results with BRCA associated protein-1 (BAP-1) expression and BAP-1 gene mutation status, monosomy 3, gene expression classifications and patient survival in uveal melanoma. The average number of cells analyzed in each of 107 tumors, was 1957 (SD 349). Mean time consumption was less than 2.5 min per tumor. Identical morphometric classification was obtained for ≥85% of tumors in all twelve evaluated morphometric variables (κ 0.70-0.93). The mean nucleus area, nucleus perimeter, nucleus max caliper and nucleus to cell area ratio were significantly greater in tumors with low BAP-1 expression and gene expression class 2. Patients had significantly shorter survival if their tumors had low BAP-1 (Log-Rank p = 0.002), gene expression class 2 (p = 0.004), long nucleus perimeters (p = 0.031), long nucleus max calipers (p = 0.029) and high mean nucleus to cell area ratios (p = 0.041) as defined in a training cohort and then tested in a validation cohort. Long nucleus perimeters and long nucleus max calipers correlated with monosomy 3 (Pearson Chi-Square p = 0.006 and p = 0.009, respectively). Long nucleus perimeters also correlated with BAP-1 mutation (p = 0.017). We conclude that digital morphometry can be fast and highly reproducible, that for the first time, morphometry parameters can be objectively quantitated in thousands of cells at a time in sub-µm resolutions, and that variables describing the shape and size tumor nuclei correlate to BAP-1 status, monosomy 3, gene expression class as well as patient survival.

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Primary ductal adenocarcinoma of the lacrimal gland: A review and report of five cases.

Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and review 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 was positive in 2 of the 4 cases. Four of the five patients were alive at the last follow-up visit. One died with bone metastases, which were diagnosed 25 months after exenteration and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Although rare, awareness and recognition of this malignancy are important to help determine prognosis and treatment options.

Should IgM/IgG rapid test kit be used in the diagnosis of COVID-19?

Key Findings@# Current evidence does NOT support use of IgM/IgG rapid test kits for the definitive diagnosis of COVID-19 in currently symptomatic patients. • The present standard for diagnosis of COVID-19 is through qualitative detection of COVID-19 virus nucleic acid via reverse transcription polymerase chain reaction (RT-PCR). • Due to long turnaround times and complicated logistical operations, a rapid and simple field test alternative is needed to diagnose and screen patients. • An alternative to the direct detection and measurement of viral load (RT-PCR) is the qualitative detection of specific antibodies to COVID-19. ELISA (discussed in a separate rapid review) and lateral flow immunoassay (LFIA) IgM/IgG rapid test kits are two currently available, qualitative, antibody tests for COVID-19. • Two low quality clinical trials showed that there is insufficient evidence to support the use of IgM/IgG rapid test kits for the definitive diagnosis of COVID-19. Diagnostic accuracy varies greatly depending on the timing of the test. The test performed very poorly during the early phase of the disease (i.e., less than eight days from onset of symptoms). • Existing guidelines do not recommend serologic antibody tests for the diagnosis of COVID-19 in currently symptomatic patients.

Density of PAS positive patterns in uveal melanoma: Correlation with vasculogenic mimicry, gene expression class, BAP-1 expression, macrophage infiltration, and risk for metastasis.

Purpose: Periodic acid-Schiff (PAS) positive patterns of vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma (UM). We examined these patterns with digital image analysis and transmission electron microscopy, and correlated them with BAP-1 expression, gene expression class, macrophage infiltration, and metastatic disease in full tumor cross-sections and intratumor regions. Methods: Thirty-two enucleated eyes with UM were stained immunohistochemically (BAP-1, laminin, CD31, and CD68) and with PAS without hematoxylin counterstain. Retrospective data on gene expression class and patient survival were retrieved. Tumor sections were digitally scanned and analyzed with the QuPath Bioimage analysis software, and imaged with transmission electron microscopy. Results: The mean area proportion covered by CD31, laminin, and PAS positive patterns in tumor cross-sections was 0.9% (SD 0.6), 3.0% (SD 1.9), and 8.4% (SD 5.9), respectively. PAS density was statistically significantly greater in tumors with gene expression class 2 (p=0.02). The cumulative 5-year metastasis-free survival decreased for each quartile of increased PAS density (1.0, 0.75, 0.40, and 0.17, p=0.004). Forty percent of the tumors had heterogeneous BAP-1 expression. Intratumor regions with low BAP-1 expression were more likely to harbor VM (p<0.0001), and had statistically significantly greater PAS density (p<0.0001) and number of CD68 positive cells (p=0.01). Conclusions: PAS positive patterns in UM are composed of a mixture of blood vessels and extracellular matrix (ECM), including VM. Increased density of PAS positive patterns correlated with gene expression class and metastasis, and colocated to tumor regions with macrophage infiltration and low BAP-1 expression.