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1.
Int Health ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962866

ABSTRACT

Respiratory viruses contribute to high morbidity and mortality in Africa. In 2020, the Ohio State University's Global One Health Initiative, in collaboration with the Ethiopian Public Health Institute and the US Centers for Disease Control and Prevention, took action to strengthen Ethiopia's existing respiratory virus surveillance system through decentralization of laboratory testing and scale-up of national and regional capacity for detecting respiratory viruses. In August 2022, four regional laboratories were established, thereby raising the number of reference laboratories conducting respiratory virus surveillance to five. This article highlights lessons learned during implementation and outlines processes undertaken for laboratory scale-up and decentralization.

2.
Pak J Med Sci ; 40(6): 1300-1302, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38952497

ABSTRACT

Approximately 3% to 4% of all newly diagnosed cancers are kidney tumours, which can develop from either the renal parenchymal tissue or the renal pelvis. Kidney cancer is one of the 13 most prevalent kinds of malignancy worldwide. 85% of all malignant kidney neoplasms are renal cell carcinomas (RCC). We present a rare instance of an RCC that had a thrombus in the ureter and had directly extended into the renal pelvicalyceal system. A thorough diagnostic workup was required because the patient had a number of symptoms, including flank pain, hematuria, and weight loss. Imaging tests identified a renal parenchymal-derived infiltrative tumour with remarkable pelvicalyceal penetration. Neovascularization was found within the tumour as a result of additional search. The discovery of ureteral extension, a peculiar characteristic, raised questions regarding both local and distant metastases. R.E.N.A.L nephrometry score was 11 with high complexity. Multidisciplinary management of the intricate clinical problem was employed. After removing the tumour mass, the ureteral involvement was treated with surgical resection, adjuvant therapy, and CT monitoring over the three-month high-risk follow-up period. With surgery, targeted treatment was employed to stop the cancer from growing. Conclusion: The importance of identifying unusual RCC presentations and employing a comprehensive diagnostic and treatment strategy is emphasised by this study. The complex interaction of ureteral extension, neovascularization, and pelvicalyceal penetration highlights the aggressiveness of advanced RCC. Since we are not aware of any literature documented instances including this combination, there are few studies explaining pelvicalyceal system invasion that defies commonly recognised diagnostic and treatment paradigms for renal cell carcinoma.

3.
Front Clin Diabetes Healthc ; 5: 1348104, 2024.
Article in English | MEDLINE | ID: mdl-38952998

ABSTRACT

Objectives: With diabetes self-management continuing to become more complex for older adults, self-management programs have been shown to support this population in meeting their multifaceted medical needs. Building on our previous systematic review and meta-analysis, we aimed to update the literature on the effectiveness of diabetes self-management programs and investigate the impact of specific self-management interventions on clinical and patient-reported outcomes. Methods: We updated our literature search in the following databases: Medline, EMBASE, PsychINFO, CINAHL and Cochrane Database of Randomized Controlled Trials from November 2013 to July 2023 for studies that may fit our inclusion criteria. Two independent reviewers screened and extracted data from the included group of studies. Results: A total of 17 studies with 21 comparison arms met the inclusion criteria, totalling 5976 older adults (3510 individuals randomized to self-management programming and 2466 to usual care). The pooled effectiveness of diabetes self-management programs in older adults on glycemic control (hemoglobin A1C) was a reduction of -0.32 (95% CI -0.44, -0.19). Specifically, the most effective approach on glycemic control (A1C) was the use of feedback (-0.52%; 95% CI -0.68, -0.36). Overall, self-management programs improved behaviour change outcomes, with feedback interventions being most effective (standardized mean difference [SMD] 0.91; 95% CI 0.39, 1.43). The effect of self-management programs on body mass index, weight and lipids were statistically and clinically significant. Conclusions: The evidence for diabetes self-management programs for older adults demonstrates a small but clinically meaningful reduction in A1C, improvement in patient-reported outcomes (behaviour, self-efficacy, knowledge), and other clinical outcomes (BMI, weight and lipids). The specific strategy used in diabetes self-management programs for older adults should be considered to achieve optimal results on outcomes.

4.
Environ Geochem Health ; 46(8): 267, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954229

ABSTRACT

This study examines the levels of heavy metals in polyculture fish (Labeo rohita, Cyprinus carpio, and Catla catla), water, and sediment in Tanda Dam, Kohat, Pakistan, aiming to understand environmental and health risks. Samples of fish, water, and sediment were collected from 3 fish farms, and heavy metal concentrations were measured using a Flame Atomic Absorption Spectrophotometer (AAS). Results reveal that C. catla exhibited significantly higher (p < 0.05) levels of Zn than other fish species. Conversely, C. carpio showed significantly higher (p < 0.05) concentrations of Pb, Cd, Cr, Mn, Cu, As, and Ni than other species. The heavy metal hierarchy in C. carpio was found to be Zn > Cu > Pb > Cr > Cd > Mn > As > Ni. While heavy metal levels in L. rohita and C. catla generally fell within reference ranges, exceptions were noted for Zn, Pb, and Cd. Conversely, in C. carpio, all metals exceeded reference ranges except for Cu and Ni. Principal Component Analysis (PCA) indicated a close relationship between water and sediment. Additionally, cluster analysis suggested that C. catla formed a distinct cluster from L. rohita and C. carpio, implying different responses to the environment. Despite concerns raised by the Geoaccumulation Index (Igeo) and Contamination Factor (CF), particularly for Cd, which exhibited a high CF. Furthermore, Hazard Index (HI) values for all three fish species were below 1, suggesting low health risks. However, elevated Igeo and CF values for Cd suggest significant pollution originating from anthropogenic sources. This study underscores the importance of monitoring heavy metals in water for both environmental preservation and human health protection. Future research efforts should prioritize pollution control measures to ensure ecosystem and public health safety.


Subject(s)
Environmental Monitoring , Geologic Sediments , Metals, Heavy , Water Pollutants, Chemical , Metals, Heavy/analysis , Animals , Water Pollutants, Chemical/analysis , Humans , Risk Assessment , Geologic Sediments/chemistry , Environmental Monitoring/methods , Pakistan , Ecosystem , Carps/metabolism , Fishes/metabolism , Principal Component Analysis , Aquaculture
5.
J Pak Med Assoc ; 74(6): 1156-1159, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948989

ABSTRACT

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.


Subject(s)
Community-Acquired Infections , Hospital Mortality , Pneumonia , Humans , Community-Acquired Infections/mortality , Male , Female , Middle Aged , Pneumonia/mortality , Cross-Sectional Studies , Pakistan/epidemiology , Adult , Severity of Illness Index , Early Warning Score , Aged
6.
Cureus ; 16(6): e61884, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975542

ABSTRACT

Background Among all the modalities of diagnostic radiology, ultrasonography is considered the least invasive one. However, this benefit usually comes at the cost of its subjective evaluation since it is purely a dynamic diagnostic modality. Thus, instead of ultrasonography, most clinicians usually rely on the report written by the radiologist. Objective The objective of this study is to evaluate the clinical practices of ultrasound reporting of superficial soft tissue masses. Materials and methods A closed-loop retrospective and prospective study was conducted at the Department of Radiology and Medical Imaging, Jinnah Hospital, Lahore between December 2023 and March 2024. In the pre-intervention phase, a randomly collected sample of 100 ultrasound reports documenting superficial soft tissue masses were included in the study and judged against standard criteria set by the Royal College of Radiologists (RCR). The intervention phase included regular presentations, identification of problems, and designing of preformed reporting forms. Post-intervention assessments were based on the judgment of 100 ultrasound reports in each cycle twice. Intervention and post-intervention assessments were done twice to correct the ongoing practices. Results During the pre-intervention phase, the ultrasound reports issued by the department of study showed only 41.5% compliance with the RCR structured reporting guidelines. However, after the first and second post-intervention phases, this percentage increased up to 98.3%. Overall, we observed a compliance difference of 56.5% between the pre-intervention and second post-intervention phases. Conclusion Integration of methods, such as briefing the residents on RCR guidelines, displaying parameters, and making structured report templates available, can greatly increase adherence to RCR guidelines for structured ultrasonography reporting. It also greatly enhances the comprehensiveness and reliability of ultrasonography reports for clinicians. Clinical audits should be routinely practiced in the settings of radiology.

7.
Int J Speech Lang Pathol ; : 1-12, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978267

ABSTRACT

PURPOSE: Urdu is the lingua franca and national language of Pakistan, and is the 10th most-spoken language worldwide with over 230 million speakers. The Urdu phonological system has been examined over the past decades. However, the system has been evolving. This paper aimed to review the available studies investigating various aspects of the Urdu phonological system and to reveal the variations noted among these studies. METHOD: Twenty-one studies examining the phonological system of Urdu were located. The studies were reviewed in terms of consonants, geminates, consonant clusters, vowels, diphthongs, syllable structure, phonotactic constraints, and stress. RESULT: The findings indicated that 38 consonants, 23 vowels, and 15 diphthongs are used in contemporary Urdu. Most consonants exist as geminates word medially. There are six syllable structures. The consonant clusters are constrained to the coda position only, and short vowels cannot exist in the word-final position. Like other syllable-timed languages, stress is not prominent in Urdu. CONCLUSION: Based on this review, a contemporary Urdu phonemic and syllable structure inventory has been proposed. This will serve as a reference for use in further acquisition research and clinical practice.

8.
PLoS One ; 19(7): e0306712, 2024.
Article in English | MEDLINE | ID: mdl-38976658

ABSTRACT

In oral pathology, virtual clinical scenario illustrating dentist-patient interactions can be utilized by both students and health professionals to deliver/gain knowledge and make clinical diagnosis of oral lesions. Role play is also an educational technique which is designed to engage and motivate students in classrooms. This study aimed to compare usefulness of virtual clinical scenario and role play in learning oral pathology among second-year dental students. The students were randomly divided to one of the two groups: virtual clinical scenario group (n = 50) and role play group (n = 50). Virtual clinical scenario group was provided with virtual clinical cases of oral lesions through Google Forms whereas role play group was exposed to virtual clinical cases of oral lesions through role playing activity. Both groups underwent assessments before and after the intervention. Students' perceptions on usefulness of both techniques in terms of diagnosis, visual parameters and impact on learning were evaluated by feedback questionnaire. Data were analyzed using Statistical Package for the Social Sciences version 27.0. Wilcoxon signed-rank test was used to compare pre-test and post-test scores. Additionally, the scores and students' responses from both groups were compared using the Mann-Whitney U test. A P-value of < 0.05 was set as statistically significant. Students in both groups showed significantly higher post-test scores compared to their pre-test scores (P < 0.001). However, the role play group outperformed the virtual clinical scenario group, with a significantly higher post-test score (P = 0.04). Furthermore, feedback concerning role play was significantly higher than that for the virtual clinical scenario across multiple aspects (P < 0.05). Our findings suggest that role play emerges as the preferred method, significantly enhancing dental students' learning experiences in oral pathology.


Subject(s)
Education, Dental , Students, Dental , Humans , Students, Dental/psychology , Education, Dental/methods , Female , Male , Pathology, Oral/education , Learning , Role Playing , Surveys and Questionnaires , Young Adult , Educational Measurement , Adult
9.
Int J Biol Macromol ; 275(Pt 1): 133571, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960243

ABSTRACT

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC50 value of 16.47 ± 0.54 µM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug development.

10.
Drugs Context ; 132024.
Article in English | MEDLINE | ID: mdl-38989131

ABSTRACT

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy. Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form. Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals. Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.

11.
Ann Diagn Pathol ; 73: 152358, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38944911

ABSTRACT

The routine histomorphological assessment of follicular thyroid neoplasms has been subject to interobserver or intraobserver variability among histopathologists. Anti-thyroid peroxidase (anti-TPO) has emerged as a useful immunohistochemical (IHC) marker, with its expression lost in papillary thyroid carcinoma (PTC). Our study aims to determine the diagnostic accuracy of anti-TPO IHC expression in the identifying PTC and its variants, particularly the Follicular variant of papillary thyroid carcinoma (FVPTC), with H&E assessment as the gold standard. Anti-TPO IHC (DAKO-MoAb47) was performed on 110 cases, including 76 malignant tumors (classic PTC, FVPTC, follicular carcinoma (FC), and oncocytic carcinoma (OC)) and 34 benign tumors (non-invasive follicular tumor with papillary-like nuclear features (NIFTP) and follicular adenoma (FA)). The loss of expression in more than or equal to 51 % of thyrocytes was considered suggestive of a PTC profile. The sensitivity of the loss of anti-TPO expression for identifying PTC among all carcinomas was 61.7 %, specificity was 75 %, positive predictive value was 90.2 %, negative predictive value was 34.2 %, and accuracy was 64.4 %. The loss of anti-TPO IHC expression combined with routine H&E assessment, supports the identification of PTC and its variants.

12.
JAMA Ophthalmol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935350

ABSTRACT

Importance: Anti-vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration. Objective: To quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices. Design, Setting, and Participants: Prospective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US. Main Outcomes and Measures: Overall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures. Results: In total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes. Conclusions and Relevance: In this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

14.
J Manag Care Spec Pharm ; 30(6): 517-527, 2024 06.
Article in English | MEDLINE | ID: mdl-38824625

ABSTRACT

BACKGROUND: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. OBJECTIVE: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. METHODS: A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. RESULTS: Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. CONCLUSIONS: Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.


Subject(s)
Antibodies, Monoclonal, Humanized , Cost-Benefit Analysis , Markov Chains , Myasthenia Gravis , Quality-Adjusted Life Years , Receptors, Cholinergic , Humans , Myasthenia Gravis/drug therapy , Myasthenia Gravis/economics , Myasthenia Gravis/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/economics , Receptors, Cholinergic/immunology , Female , Male , Middle Aged , Drug Costs , Adult , Autoantibodies
15.
Dalton Trans ; 53(27): 11295-11309, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38898716

ABSTRACT

A thiophene-derived Schiff base ligand (E)-2-morpholino-N-(thiophen-2-ylmethylene)ethanamine was used for the synthesis of M(II) complexes, [TEM(M)X2] (M = Co, Cu, Zn; X = Cl; M = Cd, X = Br). Structural characterization of the synthesized complexes revealed distorted tetrahedral geometry around the M(II) center. In vitro investigation of the synthesized ligand and its M(II) complexes showed considerable anti-urease and leishmanicidal potential. The synthesized complexes also exhibited a significant inhibitory effect on urease, with IC50 values in the range of 3.50-8.05 µM. In addition, the docking results were consistent with the experimental results. A preliminary study of human colorectal cancer (HCT), hepatic cancer (HepG2), and breast cancer (MCF-7) cell lines showed marked anticancer activities of these complexes.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Molecular Docking Simulation , Schiff Bases , Thiophenes , Urease , Humans , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Urease/antagonists & inhibitors , Urease/metabolism , Thiophenes/chemistry , Thiophenes/pharmacology , Thiophenes/chemical synthesis , Schiff Bases/chemistry , Schiff Bases/pharmacology , Schiff Bases/chemical synthesis , Morpholines/chemistry , Morpholines/pharmacology , Morpholines/chemical synthesis , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Molecular Structure , Leishmania/drug effects , Structure-Activity Relationship , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/chemical synthesis , Drug Screening Assays, Antitumor
16.
JMIR Form Res ; 8: e56241, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38917454

ABSTRACT

BACKGROUND: Accelerated digitalization in the health sector requires the development of appropriate evaluation methods to ensure that digital health technologies (DHTs) are safe and effective. Software as a medical device (SaMD) is a commonly used DHT by clinicians to provide care to patients. Traditional research methods for evaluating health care products, such as randomized clinical trials, may not be suitable for DHTs, such as SaMD. However, evidence to show their safety and efficacy is needed by regulators before they can be used in practice. Clinical simulation can be used by researchers to test SaMD in an agile and low-cost way; yet, there is limited research on criteria to assess the robustness of simulations and, subsequently, their relevance for a regulatory decision. OBJECTIVE: The objective of this study was to gain consensus on the criteria that should be used to assess clinical simulation from a regulatory perspective when it is used to generate evidence for SaMD. METHODS: An eDelphi study approach was chosen to develop a set of criteria to assess clinical simulation when used to evaluate SaMD. Participants were recruited through purposive and snowball sampling based on their experience and knowledge in relevant sectors. They were guided through an initial scoping questionnaire with key themes identified from the literature to obtain a comprehensive list of criteria. Participants voted upon these criteria in 2 Delphi rounds, with criteria being excluded if consensus was not met. Participants were invited to add qualitative comments during rounds and qualitative analysis was performed on the comments gathered during the first round. Consensus was predefined by 2 criteria: if <10% of the panelists deemed the criteria as "not important" or "not important at all" and >60% "important" or "very important." RESULTS: In total, 33 international experts in the digital health field, including academics, regulators, policy makers, and industry representatives, completed both Delphi rounds, and 43 criteria gained consensus from the participants. The research team grouped these criteria into 7 domains-background and context, overall study design, study population, delivery of the simulation, fidelity, software and artificial intelligence, and study analysis. These 7 domains were formulated into the simulation for regulation of SaMD framework. There were key areas of concern identified by participants regarding the framework criteria, such as the importance of how simulation fidelity is achieved and reported and the avoidance of bias throughout all stages. CONCLUSIONS: This study proposes the simulation for regulation of SaMD framework, developed through an eDelphi consensus process, to evaluate clinical simulation when used to assess SaMD. Future research should prioritize the development of safe and effective SaMD, while implementing and refining the framework criteria to adapt to new challenges.

17.
Hepatology ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38899967

ABSTRACT

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis. APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and HES V2.0 scores within 6, 12, and 24 months of HCC diagnosis. We calculated the AUROC curve and estimated TPR based on an optimal threshold at a fixed false-positive rate of 10%. We analyzed 2331 patients, of whom 125 developed HCC (71% in the early stages). For any HCC, HES V2.0 had higher TPR than GALAD overall (+7.2%), at 6 months (+3.6%), at 12 months (+7.2%), and 24 months (+13.0%) before HCC diagnosis. HES V2.0 had higher TPR than ASAP for all time points (+5.9% to +12.0%). For early HCC, HES V2.0 had higher sensitivity/TPR than GALAD overall (+6.7%), at 12 months (+6.3%), and 24 months (+14.6%) but not at 6 months (+0.0%) and higher than ASAP for all time points (+13.4% to +18.0%). CONCLUSIONS: In a prospective cohort study, HES V2.0 had a significantly higher performance for identifying new HCC, including early stage, than GALAD or ASAP.

18.
Environ Res ; 257: 119328, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851369

ABSTRACT

The growing effects of climate change on Malaysia's coastal ecology heighten worries about air pollution, specifically caused by urbanization and industrial activity in the maritime sector. Trucks and vessels are particularly noteworthy for their substantial contribution to gas emissions, including nitrogen dioxide (NO2), which is the primary gas released in port areas. The application of advanced analysis techniques was spurred by the air pollution resulting from the combustion of fossil fuels such as fuel oil, natural gas and gasoline in vessels. The study utilized satellite photos captured by the Tropospheric Monitoring Instrument (TROPOMI) on the Sentinel-5P satellite to evaluate the levels of NO2 gas pollution in Malaysia's port areas and exclusive economic zone. Before the COVID-19 pandemic, unrestricted gas emissions led to persistently high levels of NO2 in the analyzed areas. The temporary cessation of marine industry operations caused by the pandemic, along with the halting of vessels to prevent the spread of COVID-19, resulted in a noticeable decrease in NO2 gas pollution. In light of these favourable advancements, it is imperative to emphasize the need for continuous investigation and collaborative endeavours to further alleviate air contamination in Malaysian port regions, while simultaneously acknowledging the wider consequences of climate change on the coastal ecology. The study underscores the interdependence of air pollution, maritime activities and climate change. It emphasizes the need for comprehensive strategies that tackle both immediate environmental issues and the long-term sustainability and resilience of coastal ecosystems in the context of global climate challenges.

19.
PLoS One ; 19(6): e0303134, 2024.
Article in English | MEDLINE | ID: mdl-38837975

ABSTRACT

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 µg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells.


Subject(s)
Molecular Docking Simulation , Plant Extracts , Tumor Suppressor Protein p53 , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , MCF-7 Cells , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Female , HEK293 Cells , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism
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