Prevent Disease Progression Research Articles

Using Artificial Intelligence for Rheumatic Heart Disease Detection by Echocardiography: Focus on Mitral Regurgitation.

Identification of children with latent rheumatic heart disease (RHD) by echocardiography, before onset of symptoms, provides an opportunity to initiate secondary prophylaxis and prevent disease progression. There have been limited artificial intelligence studies published assessing the potential of machine learning to detect and analyze mitral regurgitation or to detect the presence of RHD on standard portable echocardiograms. We used 511 echocardiograms in children, focusing on color Doppler images of the mitral valve. Echocardiograms were independently reviewed by an expert adjudication panel. Among 511 cases, 229 were normal, and 282 had RHD. Our automated method included harmonization of echocardiograms to localize the left atrium during systole using convolutional neural networks and RHD detection using mitral regurgitation jet analysis and deep learning models with an attention mechanism. We identified the correct view with an average accuracy of 0.99 and the correct systolic frame with an average accuracy of 0.94 (apical) and 0.93 (parasternal long axis). It localized the left atrium with an average Dice coefficient of 0.88 (apical) and 0.9 (parasternal long axis). Maximum mitral regurgitation jet measurements were similar to expert manual measurements (P value=0.83) and a 9-feature mitral regurgitation analysis showed an area under the receiver operating characteristics curve of 0.93, precision of 0.83, recall of 0.92, and F1 score of 0.87. Our deep learning model showed an area under the receiver operating characteristics curve of 0.84, precision of 0.78, recall of 0.98, and F1 score of 0.87. Artificial intelligence has the potential to detect RHD as accurately as expert cardiologists and to improve with more data. These innovative approaches hold promise to scale echocardiography screening for RHD.

Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study

Purposeto determine whether primary trabeculectomy or medical treatment produces better outcomes in term of quality of life (QoL), clinical effectiveness and safety in patients presenting with advanced glaucoma. Designmulticentre randomised controlled trial Participantsbetween June 3, 2014 and May 31, 2017, 453 adults presenting with newly diagnosed advanced open angle glaucoma in at least one eye (Hodapp Classification) were recruited from 27 secondary care glaucoma departments in the UK, 227 were allocated to trabeculectomy and 226 to medical management. Methodsparticipants were randomised on a 1:1 basis to have either mitomycin C augmented trabeculectomy or escalating medical management with intraocular pressure reducing drops as their primary intervention and followed up for 5 years. ISRCTN registry: ISRCTN56878850. Main Outcome MeasuresThe primary outcome was vision-specific quality of life measured with Visual Function Questionnaire-25 (VFQ-25) at 5-years. Secondary outcomes: general health status, glaucoma related QoL, clinical effectiveness [intraocular pressure (IOP), visual field (VF), visual acuity (VA)] and safety. ResultsAt 5 years the mean VFQ-25 in the trabeculectomy and medication arms were 83.3 (SD 15.5) and 81.3 (SD 17.5) respectively, mean difference 1.01, (95% CI -1.99 to 4.00); p=0.51. Mean IOPs were 12.07 ( 5.18) mmHg and 14.76 (4.14) mmHg respectively, mean difference -2.56 (95% CI -3.80 to -1.32); p<0.001. Glaucoma severity measured with visual field mean deviation were -14.30 (7.14) and -16.74 (6.78) dB respectively, mean difference 1.87 (95% CI 0.87 to 2.87) dB, p<0.001. Safety events occurred in 115 (52.2%) in the trabeculectomy arm and 124 (57.9%) in the medication arm, relative risk 0.92 (95% CI 0.72 to 1.19); p=0.54. Serious adverse events were rare. ConclusionAt 5 years TAGS has demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients presenting with advanced disease and has a similar safety profile Trial registrationHealth Technology Assessment (NIHR-HTA) Programme (Project number: 12/35/38). ISRCTN registry: ISRCTN56878850.

Improving medication adherence in cardiovascular disease.

Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.

Estimation of Microalbuminuria in Children with Beta Thalassaemia Major: A Cross-sectional Study

Introduction: Improvement in the standard of care of Thalassaemia by regular blood transfusion increases life expectancy. Multiple transfusions with concurrent iron overload and chronic anaemia, leading to tissue-level hypoxemia, cause significant renal dysfunction. Microalbuminuria is a sensitive marker of glomerular damage, and studies in thalassemic children have demonstrated variable prevalence rates of microalbuminuria. Aim: To study the prevalence of microalbuminuria and its association with clinical and laboratory parameters in children with Beta Thalassaemia Major (BTM). Materials and Methods: A cross-sectional study was conducted from January 2018 to June 2019 at Indira Gandhi Institute of Child Health, Bangaluru, Karnataka,India. A total of 155 children with Beta Thalassaemia Major (BTM) aged 2-18 years, attending the Thalassaemia Day Care Centre, were included in the study. Their demographic details such as age, gender, clinical parameters like frequency of transfusions, type of chelation therapy, height, weight, Body Mass Index (BMI), organomegaly, and laboratory parameters like serum creatinine, ferritin, pretransfusion Hb%, and Urinary Microalbumin Creatinine Ratio (UMCR) were studied as per a predesigned proforma. The association between microalbuminuria with clinical and laboratory parameters was evaluated using the independent sample T-test or Mann-Whitney U test and Chi-square/Fischer’s-exact test. Results: A total of 155 children with BTM were studied. In the present study, out of a total of 155 patients, microalbuminuria was found in 66 (42.6%). A significant increase in the prevalence of microalbuminuria was observed as the age advanced, as the frequency of blood transfusions increased, with low pretranfusion haemoglobin (g%), and with elevated serum ferritin. Conclusion: In the present study, the prevalence of microalbuminuria was found to be 42.6%. Screening for microalbuminuria is recommended in all children with beta thalassaemia major for the early detection of renal dysfunction, prevention of disease progression, and improvement in the quality of their lives.

The use of antibacterial drugs for the treatment of inflammatory periodontal diseases (review)

The high prevalence of inflammatory periodontal diseases worldwide is a pressing issue in dentistry. One of the etiologic factors in the development of periodontitis is periodontopathogenic bacteria, which provoke the development of inflammation accompanied by destructive processes in the bone and connective tissue of the periodontium. The main goal of periodontal treatment is to restore the microbiological balance of periodontal tissues, eliminate periodontopathogens, prevent disease progression and restore the level of clinical attachment. The systematic review presents the results of modern studies on the use of drugs based on chlorhexidine, metronidazole and tetracycline antibiotics for the treatment of periodontitis. In view of the short-term effect of the active substance on periodontopathogenic microflora, it is necessary for domestic manufacturers to develop drugs with antibacterial activity that have a prolonged effect in periodontal tissues for the effective treatment of periodontitis.

Keratoconus: imaging modalities and management.

Keratoconus (KCN) is characterized by gradual thinning and steepening of the cornea, which can lead to significant vision problems owing to high astigmatism, corneal scarring, or even corneal perforation. The detection of KCN in its early stages is crucial for effective treatment. In this review, we describe current advances in the diagnosis and treatment of KCN. This narrative review focuses on recent advancements in the diagnosis and treatment of KCN, especially evolving approaches and strategies. To ensure the inclusion of the most recent literature, relevant publications discussing advanced imaging techniques and treatment options for KCN were extensively gathered from the PubMed/MEDLINE and Google Scholar databases. The following index terms and keywords were used for the online search: keratoconus, diagnosis of keratoconus, advances in the diagnosis of keratoconus, topography or tomography, anterior segment optical coherence tomography, treatment of keratoconus, advances in the treatment of keratoconus, collagen crosslinking, intrastromal ring, keratoplasty, and new techniques in keratoconus. Various screening methods such as corneal topography, tomography, anterior segment optical coherence tomography, and assessment of corneal biomechanics have been developed to identify KCN in its early stages. After diagnosis, KCN management focuses on preventing disease progression. Corneal collagen crosslinking is a minimally invasive treatment that can slow or stop the progression of the condition. Recent research has also explored the use of copper sulfate eye drops (IVMED-80) as a noninvasive treatment to prevent the progression of KCN. Current treatment options for visual improvement include scleral lenses, intracorneal ring segments, corneal allogeneic intrastromal ring segments, and deep anterior lamellar keratoplasty. Recently, novel alternative procedures, such as isolated Bowman layer transplantation, either as a corneal stromal inlay or onlay, have demonstrated encouraging outcomes. Artificial intelligence has gained acceptance for providing best practices for the diagnosis and management of KCN, and the science of its application is contentiously debated; however, it may not have been sufficiently developed. Early detection and advancements in screening methods using current imaging modalities have improved diagnosis of KCN. Improvement in the accuracy of current screening or diagnostic tests and comparison of their validities are achievable by well-designed, large-scale, prospective studies. The safety and effectiveness of emerging treatments for KCN are currently being investigated. There is an ongoing need for studies to track progress and evaluate clinicians' knowledge and practices in treating patients with KCN. Artificial intelligence capabilities in management approach considering the currently available imaging modalities and treatment options would best benefit the patient.

Searching for a “Window of Opportunity” in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment

Introduction: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a “window of opportunity” exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. Methods: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016–2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. Results: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. Conclusion: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a “window of opportunity” in VLS treatment.

Novel perspective of therapeutic modules to overcome motor and nonmotor symptoms in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons, which leads to motor and non-motor symptoms that have a significant impact. The pathophysiology of PD is complex and involves environmental and genetic factors that contribute to alpha-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. The current treatments of PD primarily focus on symptom management and have limitations in addressing disease progression and non-motor symptoms. Epidemiological data indicates a rise in PD cases worldwide, which highlights the need for effective treatments. Pathophysiological insights point out the involvement of various factors in PD progression, such as dopamine dysregulation, genetic mutations, oxidative stress, mitochondrial damage, alpha-synuclein aggregation, and neuroinflammation. Although current treatments, which include dopamine precursors, monoamine oxidase (MAO) inhibitors, and non-dopaminergic drugs, can alleviate motor symptoms, they are not effective in preventing disease progression or managing non-motor symptoms. Additionally, they can lead to adverse effects and become less effective over time. Novel therapeutic approaches, including cell-based therapies, gene therapies, targeted drug delivery therapies, and magnetic field therapies, are promising in improving symptom management and providing personalized treatment. Additionally, emerging therapies that target alpha-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation may have potential disease-modifying effects. To sum up, for dealing with the multiple aspects of PD, there is a great need to come up with new and creative therapeutic approaches that not only relieve symptoms, but also prevent the progression of disease and non-motor symptoms. The progress made in comprehending the underlying mechanisms of PD provides optimism for developing successful treatments that can enhance the outcomes and quality of life.

Are you giving men with heart failure the best care?

Heart failure is a leading cause of morbidity and mortality worldwide. Management involves a comprehensive multidisciplinary approach focusing on symptom control, preventing disease progression and improving patients’ quality of life. Significant advances in recent years, including the introduction of combination angiotensin receptor‐neprilysin inhibitors and sodium‐glucose co‐transporter 2 inhibitors, have led to an improvement in long‐term prognosis.

Innovative approaches to cardiovascular disease prevention based on biological research, including gene therapy and stem cells

This article discusses innovative biologic-based approaches to cardiovascular disease prevention, including gene therapy and stem cell therapy. Gene therapy offers promise for targeting genetic factors that contribute to cardiovascular disease, while stem cell therapy holds promise for tissue regeneration and repair. The article highlights the role of these advanced approaches in promoting cardiovascular health and preventing disease progression. The importance of ongoing biological research in developing effective measures to prevent cardiovascular disease is also discussed.

Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

Relationship of intraocular pressure with age, blood pressure, and central corneal thickness in subjects with open-angle glaucoma

Background: Glaucoma, a chronic optic neuropathy, is the leading cause of irreversible blindness globally. The difficulties in the identification and treatment of open-angle glaucoma lie in the multifactorial nature of the disease, including individual variations, various risk factors, and the need for personalized treatment plans. Lowering intraocular pressure (IOP) is the only proven treatment for glaucoma, and controlling its fluctuations is crucial in preventing disease progression. Aims and Objectives: This study aimed to evaluate the association between IOP and various factors in primary open-angle glaucoma (POAG) subjects and compare it to control subjects. Materials and Methods: The study utilized a case–control design that included a total of 144 participants, divided into two groups: 72 individuals recently diagnosed with POAG and 72 apparently healthy subjects without glaucoma. The age range of the participants was between 40 and 75 years old, and both sexes were represented in the study. The factors examined were age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and central corneal thickness (CCT). Results: The results of the study showed that individuals with POAG had significantly higher IOP, older age, higher SBP, and higher DBP compared to the control group. In addition, CCT was significantly lower in the POAG group. There were significant positive correlations between IOP and SBP, DBP, and CCT in both the POAG and control groups. There was also a significant negative correlation between age and IOP in both the groups. Conclusion: Determination of a target IOP and achieving the set target IOP does not give complete assurance that glaucoma progression will be prevented, as many other factors also play a part in it. The findings of this study highlight the importance of considering these factors when determining the target IOP for glaucoma treatment.

Impact of Wearable Technology on Heart Failure Management.

Heart failure (HF) is a chronic and progressive condition that its management presents significant challenges in both clinical settings and patient self-care. Recent advances in wearable technology offer promising solutions to these challenges by enabling continuous monitoring, early detection of clinical deterioration, and personalized care. This review aims to critically evaluate the impact of wearable technology on HF management Materials and Methods: This narrative systematic review was conducted across multiple databases, including PubMed, Web of Science, and the Cochrane Library, to identify relevant studies published between 2010 and 2024. Studies on wearable devices for HF management and monitoring were included if they reported on clinical trials and provided data on integration into clinical workflows. Studies on other conditions or without original research data or Non-English papers were excluded. Nine studies were evaluated in this study that were focusing on a variety of technologies ranging from consumer-grade fitness trackers to specialized bioimpedance sensors and wearable cardioverter-defibrillators. These studies demonstrate the potential of wearables to continuously monitor important health metrics, which can lead to early intervention and personalized care. However, there are still challenges to be addressed, including concerns about data accuracy, patient adherence, small sample sizes, and the incorporation of wearable data into clinical practice. While consumer devices are more accessible, their accuracy in a clinical setting is uncertain, while more advanced devices like the "Volum" monitor and BioZ sensors show promise but require further validation. This review highlights the growing importance of wearable technologies in HF management, actionable insights that can prevent disease progression. However, significant challenges remain, including the need for further validation, device optimization, and data standardization before routine clinical practice. Future advancements should focus on improving device accuracy, patient adherence, and data security, while ensuring equitable access to these technologies.

The safety and efficacy of imatinib a tyrosine kinase inhibitor for the treatment of SARS-COV-2 induced pneumonia: a pilot study

Introduction Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a wide spectrum of disease, approximately 15–20% of affected patients present with severe phenotype that require supplemental oxygen, including up to 5% who may develop critical illness. The main therapeutic strategies proposed for the management of COVID-19 pneumonia are direct antiviral and immunomodulatory treatments aiming to prevent disease progression. In this pilot study we are testing the hypothesis of using imatinib a tyrosine kinase inhibitor (TKI) as an immunomodulatory treatment to prevent disease progression, based on encouraging data from cellular, animal models and clinical trials, showing a beneficial role of TKI in the regulation of inflammation and endothelial barrier integrity, as well as their antiviral properties. Aim The primary end point is to assess the effect of the imatinib treatment, in terms of safety and efficacy, to prevent the progression of patients with moderate to severe COVID-19 pneumonia into critical illness and need for invasive mechanical ventilation. The secondary end point is a composite of change in clinical, laboratory and radiological parameters, including: clinical parameters − the percentage of patients reaching normal hypoxic index (HI) at time of hospital discharge, hospital length of stay and days on mechanical ventilation (MV) in patient intubated and mechanically ventilated, the changes in the levels of laboratory inflammatory markers: serum ferritin, serum C reactive protein (CRP), serum interleukin 6 (IL6), viral clearance presented by the delta time till negative SARS-CoV-2 PCR results, as well as the change in the chest radiological parameters (Computed tomography chest or radiography). Methods Thirty SARS-COV-2 positive patients with moderate to severe respiratory symptoms, were enrolled and randomized into three groups: group 1 Control, group 2 Low dose Imatinib (receiving 200 mg Imatinib/day) and group 3 Standard dose Imatinib (receiving 400 mg Imatinib/day). Results There was no significant difference between the three groups regarding the severity of the disease at baseline, as assessed by clinical, laboratory and radiological parameters. There was a nonstatistically significant difference in the primary end point of the study, regarding the number of patients in need for invasive mechanical ventilation, between the control group and the intervention groups receiving imatinib. Conclusion Despite the negative results regarding the efficacy of imatinib to flatten the curve of the illness and the prevention of more severe phenotype of the disease, our study showed positive findings regarding the medication’s safety and patients’ tolerability. These finding would pave the way for further studies to assess the concept of immunomodulation in the treatment of immunity derived disease, like sepsis and acute respiratory distress syndrome (ARDS).

Incorporation of Chest Computed Tomography Quantification to Predict Outcomes for Patients on Hemodialysis with COVID-19

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients. Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People’s Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models. Results: The median dialysis duration was 48 (interquartile range, 24–96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes. Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

Characteristics and antiviral treatment eligibility of patients diagnosed with hepatitis B at a teaching hospital in Ghana: Implications for prevention and management.

Hepatitis B virus (HBV) infection poses a considerable public health challenge in limited-resource settings especially in the sub-Saharan African region. Even though HBV infection is incurable, timely treatment is effective in preventing disease progression to liver cirrhosis or hepatocellular carcinoma. However, not all infected patients require treatment. The aim of the study was to determine the clinical, immunological, and virological profiles of treatment naïve patients with HBV infection, seen at the outpatient clinic of the Cape Coast Teaching Hospital. Additionally, the study sought to determine the antiviral treatment eligibility rate based on the 2015 guidelines of the World Health Organization (WHO) compared with the new 2024 guidelines. A hospital-based cross-sectional study involving total sampling of 220 treatment naïve HBV surface antigen positive clients was carried out. A structured questionnaire was used to collect data that were analyzed with STATA version 16. The median age at diagnosis was 34 years (IQR 26.0-41.5) with a male to female ratio of 1:1.5. A total of 138 participants (62.7%) were diagnosed with HBV infection following voluntary testing. There was a median delay of 8.5 months (IQR 3.0-22.5) between initial diagnosis and patients' presentation for medical care. In all, 24 patients (10.9%) had abnormal clinical examination findings, 172 patients (78.2%) had HBV DNA levels ≤ 2000 IU/ml whereas 8 (3.6%) were seropositive for the HBV envelope antigen. A few patients had concomitant human immunodeficiency virus (2.7%) and hepatitis C virus (1.4%) infections. Treatment eligibility rate based on the WHO 2015 guidelines was 6.4% (n = 14), however, with the updated 2024 guidelines, treatment eligibility was 42.3% (n = 93). Increasing the screening rate among the general population, early linkage to clinical care of screen positives and vaccination of screen negatives will help reduce HBV-related clinical conditions in resource-limited settings.

The Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study.

To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC. From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed. Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration. Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression.

Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

Applications of artificial intelligence in emergency and critical care diagnostics: a systematic review and meta-analysis.

Artificial intelligence has come to be the highlight in almost all fields of science. It uses various models and algorithms to detect patterns and specific findings to diagnose a disease with utmost accuracy. With the increasing need for accurate and precise diagnosis of disease, employing artificial intelligence models and concepts in healthcare setup can be beneficial. The search engines and databases employed in this study are PubMed, ScienceDirect and Medline. Studies published between 1st January 2013 to 1st February 2023 were included in this analysis. The selected articles were screened preliminarily using the Rayyan web tool, after which investigators screened the selected articles individually. The risk of bias for the selected studies was assessed using QUADAS-2 tool specially designed to test bias among studies related to diagnostic test reviews. In this review, 17 studies were included from a total of 12,173 studies. These studies were analysed for their sensitivity, accuracy, positive predictive value, specificity and negative predictive value in diagnosing barrette's neoplasia, cardiac arrest, esophageal adenocarcinoma, sepsis and gastrointestinal stromal tumors. All the studies reported heterogeneity with p-value <0.05 at confidence interval 95%. The existing evidential data suggests that artificial intelligence can be highly helpful in the field of diagnosis providing maximum precision and early detection. This helps to prevent disease progression and also helps to provide treatment at the earliest. Employing artificial intelligence in diagnosis will define the advancement of health care environment and also be beneficial in every aspect concerned with treatment to illnesses.

Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

Abstract Background Diagnosing latent tuberculosis (TB) infection (LTBI) and active TB (ATB) is crucial for preventing disease progression and transmission. However, current diagnostic tests have limitations in terms of accuracy and sensitivity, making it challenging to diagnose these different infection states. Therefore, this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests. Methods We developed a novel multiepitope-based diagnostic biomarker (MEBDB) from LTBI region of differentiation antigens using bioinformatics and immunoinformatics. Immune responses induced by MEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays. This study was conducted from April 2022 to December 2022 in the Senior Department of Tuberculosis at the 8th Medical Center of PLA General Hospital, China. Blood samples were collected from participants with ATB, individuals with LTBI, and healthy controls (HCs). The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves. Results A novel MEBDB, designated as CP19128P, was generated. CP19128P comprises 19 helper T lymphocyte epitopes, 12 cytotoxic T lymphocyte epitopes, and 8 B-cell epitopes. In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses. CP19128P generated significantly higher levels of tumor necrosis factor (TNF-α), interleukin 4 (IL-4), and IL-10 in ATB patients (n = 7) and LTBI (n = 8) individuals compared with HCs (n = 62) (P &lt; 0.001). Moreover, CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity. Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs (the area under the receiver operating characteristic curve [AUC], 0.976 [95% confidence interval [CI], 0.934–1.000] or 0.986 [0.956–1.000]), whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs (AUC, 0.887 [0.782–0.993] or 0.984 [0.958–1.000]). Conclusions Our study revealed that CP19128P is a potential MEBDB for the diagnosis of LTBI and ATB. Our findings suggest a promising strategy for developing novel, accurate, and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.