Evaluation of Patient Experiences with PocDoc, a Web-Based Eye Screening Tool.

INTRODUCTION: The efficacy of diagnostic and monitoring tools in ophthalmology is significantly influenced by patient engagement levels. This presents a notable challenge, especially in the context of developing tools designed for telemedicine applications. Ensuring consistent patient engagement is therefore crucial for the accurate and reliable utilization of these technologies. This study assesses patient perceptions and experiences after using a purpose-built web application, called PocDoc. METHODS: A cross-sectional questionnaire-based survey was conducted among 440 patients recruited from general and specialist eye clinics between March 2022 and October 2023, both before and after using the PocDoc app. RESULTS: Pre-test findings revealed that 86.8% of patients thought that a remote eye monitoring application would have use, while 70.9% anticipated frequent usage. Only 16.4% found it overly complex, and 55.2% perceived it as easy to use. Additionally, 34.5% foresaw the need for technical support, while 72.5% believed they would quickly grasp its use. In the post-test questionnaire, 63.3% of patients still expressed intent for frequent PocDoc usage. The perception of complexity decreased to 20.4%, with 79.3% finding it easy to use. The belief in the need for technical support decreased to 36.5%, while 89.9% felt confident in mastering the application quickly. Moreover, 77.3% found the application's functions well-integrated, and 64.6% were very confident using PocDoc. CONCLUSIONS: Results suggest patient receptivity to web-based applications, confirming their viability for specific patient groups. Overall, our study contributes to the growing body of evidence indicating that greater exposure to digital health tools can significantly influence patient acceptance and perceived ease of use, an insight that has important implications for the implementation and design of these technologies in clinical settings.

Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells.

Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.

Focal Hepatocellular Carcinoma in Pancreas.

A 67-year-old man was found to have a pancreatic head mass on abdominal ultrasound. He had compensated liver cirrhosis due to hepatitis C. The fine-needle aspiration (FNA) biopsy of the mass reported an adenocarcinoma of the pancreas, while the subsequent histopathology report of the supraclavicular lymph node showed features of hepatocellular carcinoma (HCC). A second read and additional stains on the FNA specimen confirmed a hepatoid (hepatocellular) carcinoma of the pancreas. He received atezolizumab and bevacizumab and had a good response. Tumors with features of HCC outside of the liver rarely occur and even more rarely in pancreas, with less than 50 cases reported so far. Pure HCC-like morphology is the most common histological form among four subtypes and has a relatively better prognosis. Surgical resection is considered the treatment of choice if amenable and variable outcomes are reported with different chemotherapies. Challenges exist in the diagnosis and the management of this rare and intriguing entity, and the potential misdiagnosis can have grave consequences as the management is completely different for a pancreatic adenocarcinoma and hepatoid carcinoma. We report a case with a challenging diagnosis of metastatic pancreatic hepatoid carcinoma which was treated as unresectable HCC with immunotherapy and the patient had a good response.

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Due to the important role that the Human Leukocyte Antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising a total of 5,159 cases and 27,459 controls, including the prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Effects of Different Parameter Settings for 3D Data Smoothing and Mesh Simplification on Near Real-Time 3D Reconstruction of High Resolution Bioceramic Bone Void Filling Medical Images.

Three-dimensional reconstruction plays a vital role in assisting doctors and surgeons in diagnosing the healing progress of bone defects. Common three-dimensional reconstruction methods include surface and volume rendering. As the focus is on the shape of the bone, this study omits the volume rendering methods. Many improvements have been made to surface rendering methods like Marching Cubes and Marching Tetrahedra, but not many on working towards real-time or near real-time surface rendering for large medical images and studying the effects of different parameter settings for the improvements. Hence, this study attempts near real-time surface rendering for large medical images. Different parameter values are experimented on to study their effect on reconstruction accuracy, reconstruction and rendering time, and the number of vertices and faces. The proposed improvement involving three-dimensional data smoothing with convolution kernel Gaussian size 5 and mesh simplification reduction factor of 0.1 is the best parameter value combination for achieving a good balance between high reconstruction accuracy, low total execution time, and a low number of vertices and faces. It has successfully increased reconstruction accuracy by 0.0235%, decreased the total execution time by 69.81%, and decreased the number of vertices and faces by 86.57% and 86.61%, respectively.

Racial Differences in Prevalence and Treatment for Psoriatic Arthritis and Ankylosing Spondylitis by Insurance Coverage in the USA.

INTRODUCTION: Patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) may receive suboptimal care, and differences in care by race/ethnicity, sex, and insurance coverage are not well studied. METHODS: This was a descriptive, retrospective cross-sectional US claims database analysis utilizing the Medicaid multi-state segment of the IBM® MarketScan® Commercial Claims and Encounters Supplemental Database and Optum Insight Clinformatics® Data Mart database for 2019. Patients aged ≥ 18 years with PsA or AS and continuous medical and pharmacy coverage were included. Outcomes evaluated were prevalence and percentage of patients receiving biologic disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) or visiting a rheumatologist. Outcomes were stratified by race/ethnicity, sex, and insurance coverage, with outcomes determined for commercial insurance, Medicare, and Medicaid enrollees. Differences observed in outcomes were numerical in nature. RESULTS: Prevalences of PsA and AS were highest for Medicare enrollees (320 and 156 per 100,000 persons [0.32 and 0.16%], respectively) and lowest for Medicaid enrollees (132 and 71 per 100,000 persons [0.13 and 0.07%], respectively). White patients had the greatest prevalence versus patients of other races/ethnicities. Females had a higher prevalence of PsA than males, while AS prevalence was generally lower for females versus males for each insurance category. The percentage of patients prescribed bDMARDs/tsDMARDs was highest for commercial insurance enrollees (PsA 63%, AS 43%) and lowest for Medicare enrollees (PsA 21%, AS 11%). The proportion of patients who saw a rheumatologist was lower for Medicaid enrollees (PsA 12%, AS 10%) than for commercial insurance or Medicare enrollees (PsA 68%, 55%; AS 67%, 42%). For commercial insurance and Medicare enrollees, the percentage of patients visiting a rheumatologist was similar by race/ethnicity but higher for females versus males. CONCLUSIONS: The prevalence and treatment of PsA and AS differs by race/ethnicity, insurance coverage, and sex in the USA. Efforts for improving access to care are needed to improve outcomes among all patients.

Severe retinal vasculitis in systemic lupus erythematosus leading to vision threatening paracentral acute middle maculopathy.

Systemic lupus erythematosus can affect any organ system at presentation and throughout its course. Lupus retinal vasculitis is responsible for the visual loss of variable severity and typically ascribed to the involvement of pre-capillary superficial arterial vasculature. Using multimodal imaging techniques and electrophysiology, we demonstrate the first-ever case of severe lupus retinal vasculitis resulting in the rare association of paracentral acute middle maculopathy. The findings showcase the involvement of both superficial and deep retinal capillary vasculature and the localisation of retinal dysfunction. This precise evaluation facilitated the timely use of combination immunomodulatory therapy with localised pan-retinal laser photocoagulation, resulting in the preservation of vision.

The reproduction of human pathology specimens using three-dimensional (3D) printing technology for teaching purposes.

The teaching of medical pathology has undergone significant change in the last 30-40 years, especially in the context of employing bottled specimens or 'pots' in classroom settings. The reduction in post-mortem based teaching in medical training programs has resulted in less focus being placed on the ability of students to describe the gross anatomical pathology of specimens. Financial considerations involved in employing staff to maintain bottled specimens, space constraints and concerns with health and safety of staff and student laboratories have meant that many institutions have decommissioned their pathology collections. This report details how full-colour surface scanning coupled with CT scanning and 3 D printing allows the digital archiving of gross pathological specimens and the production of reproductions or replicas of preserved human anatomical pathology specimens that obviates many of the above issues. With modern UV curable resin printing technology, it is possible to achieve photographic quality accurate replicas comparable to the original specimens in many aspects except haptic quality. Accurate 3 D reproductions of human pathology specimens offer many advantages over traditional bottled specimens including the capacity to generate multiple copies and their use in any educational setting giving access to a broader range of potential learners and users.

Clinical characteristics and predictors of 5-year survival among colorectal cancer patients in a tertiary hospital in Malaysia.

BACKGROUND: Colorectal cancer is the second most common cancer in Malaysia. Its disease burden is likely to increase over time owing to its current trends in this region. This study was undertaken to determine the 5-year survival rate and prognostic factors for survival in colorectal cancer patients treated in a tertiary hospital, in Malaysia. METHODS: We reviewed the records of colorectal cancer patients treated in Hospital Tuanku Ja'afar Seremban, Malaysia from 2008 to 2012. Survival analysis at five years was performed using the Kaplan-Meier method. Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival. RESULTS: Of the 275 patients, 43.3% were colon cancers, 51.8% were rectal cancers. Only 2.2% were diagnosed in Stage I. 28.7%, 33.1%, and 16.7% were in Stage II, III and IV respectively; 62/79 (78%) of Stage II patients were in Stage IIb; 15.7% of patients were below the age of 50 and fewer of them presented early (P=0.002). The overall 5-year survival was 46.5%. It was 67.9%, 50.5% and 12.8% for Stage I&II, III and IV patients respectively. Early stage of cancer (P<0.001) and age below the mean (P=0.01) were the most significant factor in predicting better survival. Gender and ethnic group were not associated with late presentation nor survival. Neither was there a difference between colon and rectum cancers nor patients who received elective surgical treatment compared to patients receiving other treatment first (P=0.085). CONCLUSIONS: Late presentation is the most important predictor for poor outcome for colorectal cancer in Seremban. Patients under the age of 50 years present late more often, but do not have poorer survival.

The potential deployment of a pan-tuberculosis drug regimen in India: A modelling analysis.

There is increasing interest in future, highly-potent 'pan-TB' regimens against tuberculosis (TB), that may be equally effective in both drug-susceptible and rifampicin-resistant (RR) forms of TB. Taking the example of India, the country with the world's largest burden of TB, we show that adoption of these regimens could be: (i) epidemiologically impactful, and (ii) cost-saving to the national TB programme, even if the regimen itself is more costly than current TB treatment. Mathematical modelling suggests that deployment of a pan-TB regimen in 2022 would reduce the annual incidence of TB in 2030 by 23.9% [95% Bayesian credible intervals [CrI] 17.6-30.8%] if used to treat all TB cases, and by 2.30% [95% CrI 1.57-3.48%] if used to treat only RR-TB. Notably, with a regimen costing less than USD 359 (95% CrI 287-441), treating all diagnosed TB cases with the pan-TB regimen yielded greater cost-savings than treating just those diagnosed with RR-TB. One limitation of our approach is that it does not capture the risk of resistance to the new regimen. We discuss ways in which this risk could be mitigated using modern adherence support mechanisms, as well as drug sensitivity testing at the point of TB diagnosis, to prevent new resistant forms from becoming established. A combination of such approaches would be important for maximising the useful lifetime of any future regimen.

The impact of the COVID-19 epidemic on tuberculosis control in China.

BACKGROUND: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country. METHODS: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline. FINDINGS: The notified number of TB patients decreased sharply in the 1st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19. INTERPRETATION: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established. FUNDING: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).

Temporal Factors and Missed Doses of Tuberculosis Treatment. A Causal Associations Approach to Analyses of Digital Adherence Data.

Rationale: Tuberculosis treatment lasts for 6 months or more. Treatment adherence is critical; regimen length, among other factors, makes this challenging. Globally, analyses mapping common types of nonadherence are lacking. For example, is there a greater challenge resulting from early treatment cessation (discontinuation) or intermittent missed doses (suboptimal dosing implementation)? This is essential knowledge for the development of effective interventions and more "forgiving" regimens, as well as to direct national tuberculosis programs.Objectives: To granularly describe how patients take their tuberculosis medication and the temporal factors associated with missed doses.Methods: The present study included patients with pulmonary tuberculosis enrolled in the control arm of a pragmatic, cluster-randomized trial in China of electronic reminders to improve treatment adherence. Treatment was the standard 6-month course (180 d), dosed every other day (90 doses). Medication monitor boxes recorded adherence (box opening) without prompting reminders. Patterns of adherence were visualized and described. Mixed-effects logistic regression models examined the temporal factors associated with per-dose suboptimal dosing implementation, adjusting for clustering within a participant. Cox regression models were used to examine the association between early suboptimal dosing implementation and permanent discontinuation.Results: Across 780 patients, 16,794 (23.9%) of 70,200 doses were missed, 9,487 of which were from suboptimal dosing implementation (56.5%). By 60 days, 5.1% of participants had discontinued, and 14.4% had discontinued by 120 days. Most participants (95.9%) missed at least one dose. The majority of gaps were of a single dose (71.4%), although 22.6% of participants had at least one gap of 2 weeks or more. In adjusted models, the initiation-continuation phase transition (odds ratio, 3.07 [95% confidence interval, 2.68-3.51]) and national holidays (1.52 [1.39-1.65]) were associated with increased odds of suboptimal dosing implementation. Early-stage suboptimal dosing implementation was associated with increased discontinuation rates.Conclusions: Digital tools provide an unprecedented step change in describing and addressing nonadherence. In our setting, nonadherence was common; patients displayed a complex range of patterns. Dividing nonadherence into suboptimal dosing implementation and discontinuation, we found that both increased over time. Discontinuation was associated with early suboptimal dosing implementation. These apparent causal associations between temporal factors and nonadherence present opportunities for targeted interventions.Clinical trial registered with the ISRCTN Registry (ISRCTN46846388).

Added Value of Comprehensive Program to Provide Universal Access to Care for Sputum Smear-Negative Drug-Resistant Tuberculosis, China.

The increase in drug-resistant tuberculosis in China calls for scaling up rapid diagnosis. We evaluated introduction of rapid resistance testing by line-probe assay for all patients with a diagnosis of pulmonary tuberculosis in 2 prefectures in middle and eastern China. We analyzed sputum samples for smear-positive patients and cultures for smear-negative patients. We used a before-after comparison of baseline and intervention periods (12 months each) and analyzed data for 5,222 baseline period patients and 4,364 intervention period patients. The number of patients with rifampin resistance increased from 30 in the baseline period to 97 in the intervention period for smear-positive patients and from 0 to 13 for smear-negative patients, reflecting a low proportion of positive cultures (410/2,844, 14.4%). Expanding rapid testing for drug resistance for smear-positive patients resulted in a 3-fold increase in patients with diagnoses of rifampin-resistant tuberculosis. However, testing smear-negative patients had limited added value because of a low culture-positive rate.

Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein.

Viruses utilize a number of host factors in order to carry out their replication cycles. Influenza A virus (IAV) and human respiratory syncytial virus (RSV) both infect the tissues of the respiratory tract, and as such we hypothesize that they might require similar host factors. Several published genome-wide screens have identified putative IAV host factors; however, there is significant discordance between their hits. In order to build on this work, we integrated a variety of "OMICS" data sources using two complementary network analyses, yielding 51 genes enriched for both IAV and RSV replication. We designed a targeted small interfering RNA (siRNA)-based assay to screen these genes against IAV under robust conditions and identified 13 genes supported by two IAV subtypes in both primary and transformed human lung cells. One of these hits, RNA binding motif 14 (RBM14), was validated as a required host factor and furthermore was shown to relocalize to the nucleolus upon IAV infection but not with other viruses. Additionally, the IAV NS1 protein is both necessary and sufficient for RBM14 relocalization, and relocalization also requires the double-stranded RNA (dsRNA) binding capacity of NS1. This work reports the discovery of a new host requirement for IAV replication and exposes a novel example of interplay between IAV NS1 and the host protein, RBM14.IMPORTANCE Influenza A virus (IAV) and respiratory syncytial virus (RSV) present major global disease burdens. There are high economic costs associated with morbidity as well as significant mortality rates, especially in developing countries, in children, and in the elderly. There are currently limited therapeutic options for these viruses, which underscores the need for novel research into virus biology that may lead to the discovery of new therapeutic approaches. This work extends existing research into host factors involved in virus replication and explores the interaction between IAV and one such host factor, RBM14. Further study to fully characterize this interaction may elucidate novel mechanisms used by the virus during its replication cycle and open new avenues for understanding virus biology.

Diagnostic Laboratories in India: Investigating Quality Characteristics, Productivity and Time of Reporting.

This is the result of a Survey of diagnostics laboratories in the Asia Pacific (APAC) region with perspectives on India, investigating the three key aspects that are central to the success of a laboratory: quality, cost and speed. This Survey provides a comparison in selected performance indicators in a large number of diagnostic laboratories in a broad range of countries in the APAC region. The Survey provides data on some key performance characteristics such as quality improvement activities, staff productivity and Turnaround Time (TAT). This Survey also demonstrates in India the common issues facing all the laboratories surveyed but also common solutions using a Quality Systems approach which involves Accreditation, customer responsiveness, greater use of IT, automation and Lean principles. Indian laboratories reported less automation and fewer laboratories have Laboratory Information Systems. The productivity by various measures in Indian laboratories was less than in other APAC laboratories. TAT was more commonly monitored in the Indian specimens though there were fewer laboratories compared with the APAC specimens where there were separate TATs for Short Turnaround Time and Routine specimens.

Application of 21-gene recurrence score results and ASTRO suitability criteria in breast cancer patients treated with intraoperative radiation therapy (IORT).

BACKGROUND: American Society for Radiation Oncology (ASTRO) suitability criteria for accelerated partial breast irradiation (APBI) and the 21-gene recurrence score (RS) were evaluated for prognostic and predictive benefit in IORT patients. METHODS: Outcomes of 184 patients completing IRB approved IORT protocol were retrospectively reviewed. Data included demographics, histopathology, RS, adjuvant therapy, locoregional (LRR) and distant recurrences (DR), and breast cancer-specific survival. RESULTS: There were 10 (5.4%) breast cancer recurrences, including one breast cancer-specific death. All 184 patients were classified by ASTRO suitability criteria (suitable: 64% (5 LRR), cautionary: 30% (3 LRR), unsuitable: 6.0% (1 LRR, 1 DR leading to death). RS were available in 114 estrogen receptor positive patients (<11: 22% (1 LRR), 11-25: 63% (1 LRR), 26-30: 9%, >30: 6%). Mean follow-up was 55 months. CONCLUSIONS: ASTRO suitability criteria for APBI and RS were useful in making prognostic and therapeutic recommendations for patients considering IORT.