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Effect Of Eight Hours Per Day Of Intermittent Self Prone Positioning For Seven Days On The Severity Of Covid-19 Pneumonia/ Acute Respiratory Distress Syndrome

J Ayub Med Coll Abbottabad. 2023 Feb-Mar;35(1):68-75. doi: 10.55519/JAMC-01-11069.

ABSTRACT

BACKGROUND: Prone positioning improves ventilation-perfusion mismatch, distribution of gravitational gradient in pleural pressure, and oxygen saturation significantly in patients with Covid pneumonia. We aimed to find out the efficacy of eight hours per day of intermittent selfprone positioning for seven days in patients affected with COVID-19 pneumonia/ ARDS.

METHODS: This Randomized Clinical Trial was conducted in the Covid isolation wards of Ayub Teaching Hospital, Abbottabad. Patients suffering from COVID-19 pneumonia/ ARDS were enrolled with permuted block randomization into a control and an experimental group each consisting of 36 patients. Parameters of Pneumonia Severity Index (PSI) score along with other sociodemographic data was noted on a preformed structured questionnaire. Death was confirmed by requesting the death certificate of patients on the 90th day of enrolment. Data Analysis was done with SPSS Version 25. Tests of significance were applied to calculate the difference in the patients of the two groups with respect to respiratory physiology and survival.

RESULTS: The mean age of the patients was 63.79±15.26 years. A total of 25 (32.9%) male and 47 (61.8%) female patients were enrolled. Statistically significant improvement was found in the respiratory physiology of the patients at 7th and 14th DOA between the groups. Pearson Chi-Square test of significance showed a difference in mortality between the two groups at 14th DOA (pvalue=0.011) but not at 90th DOA (p-value=0.478). Log Rank (Mantel-Cox) test of significance, applied on the Kaplan Meier curve and showed no statistically significant difference among the groups based on the survival of the patients. (p-value=0.349).

CONCLUSIONS: Early transient improvement in respiratory physiology and mortality does occur with 8 hours of self-prone positioning for seven days but there is no effect on the 90-day survival of the patients. Thus, the impact of the manoeuvre on improving survival needs to be explored with studies having an application of the manoeuvre for a longer duration and period.

PMID:36849380 | DOI:10.55519/JAMC-01-11069

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Frequency Of Stone Clearance After Transurethral Fragmentation Of Large Urinary Bladder Calculi Using Pneumatic Swiss Lithoclast

J Ayub Med Coll Abbottabad. 2023 Feb-Mar;35(1):50-53.

ABSTRACT

BACKGROUND: Vesical calculi refer to stones in the urinary bladder. The causes of bladder stones include bladder outlet obstruction, neurogenic voiding dysfunction, infection, or foreign bodies. Very rarely, these vesical calculi may reach very large sizes and the largest dimension can sometimes reach 13 centimetres.

METHODS: This descriptive cross-sectional study was conducted from 1ST May 2019 to 31st October, 2019 at Institute of Kidney Diseases, Urology Department, Hayatabad Peshawar. 164 patients with vesical stone were included in study. Ultrasound-KUB was used for diagnosis of vesical stone and after informed consent, and they underwent transurethral nephroscopic lithotripsy via the pneumatic Swiss Lithoclast.

RESULTS: Frequency of stone clearance was 96.34%. No statistically significant association of stone clearance was observed with age, gender, number of stones or max dimension of largest stone in the bladder (p>0.05).

CONCLUSIONS: Transurethral nephroscopic pneumatic lithotripsy via pneumatic Swiss Lithoclast is safe and effective procedure for treatment of large vesical stones. However, this being the first such study in adults, more data is needed to confirm these findings.

PMID:36849376

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Outcome Of The Distal Radius Fractures Managed With Across Wrist External Fixator Vs Buttress Plates

J Ayub Med Coll Abbottabad. 2023 Feb-Mar;35(1):32-36. doi: 10.55519/JAMC-01-10605.

ABSTRACT

BACKGROUND: Distal radius fracture is one of the most common injuries presented to emergency department and can be presented in any age group. In young patients the most common cause is Road Traffic Accident (RTA), while old patient history of fall is the most common cause. Different surgical options are available to treat this injury. This study aims to compare the outcome of volar buttress plate vs across wrist external fixator for Arbeitsgemeinschaft für Osteosynthesefragen (AO) type C2/C3 fracture of the distal radius.

METHODS: A retrospective comparative study between July 2020 to June 2021 at Ghurki Trust Teaching Hospital was done and a total of 50 patients who underwent surgical intervention for AO C2/C3 fracture of the distal Radius, were included. The follow-up period was 12 weeks. QuickDASH score was used to find out patient’s functional outcomes. Functional outcome was analyzed between the two groups using Mann-Whitney U test, using SPSS version 21.

RESULTS: There was no significant statistical difference between the functional outcome of patients with distal radius fracture treated with across wrist external fixator vs volar buttress plate, in term of QuickDASH score. Furthermore, age and gender also were having no effect on functional outcome in our population.

CONCLUSIONS: Across wrist external fixator is a reasonable option for AO C2/C3 type fractures of the distal radius with comparable results with volar buttress plate. It is the procedure of choice in high volume tertiary care hospitals like Gurki Trust Teaching hospital as it saves time, have similar functional outcome score, no need to re-open for removal of implant, less chances of tendon rupture as compared to volar buttress plate for distal radius fracture.

PMID:36849373 | DOI:10.55519/JAMC-01-10605

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Efficacy Of Sub-Tenon’s Block In Paediatric Strabismus Surgery In Terms Of Reduction In Oculocardiac Reflex

J Ayub Med Coll Abbottabad. 2023 Feb-Mar;35(1):3-6. doi: 10.55519/JAMC-01-11512.

ABSTRACT

BACKGROUND: Strabismus is a common disease entity in paediatric age group usually requiring surgical intervention under general anaesthesia and Oculocardiac reflex is the most dangerous complications intraoperatively. Various anaesthetic options have been evaluated to mitigate this complication. The objective of this study was to assess the efficacy of sub-tenon’s block in paediatric strabismus surgery in terms of reduction in oculocardiac reflex.

METHODS: This prospective Randomized control trial was conducted at Department of ophthalmology, MTI, Hayatabad Medical complex, Peshawar over a period of six months from 1st July to 31st December 2021. A total of 124, were equally divided in subtenon’s group (Group A) and placebo group (Group B). Intraoperatively, patients were assessed for Bradycardia and development of OCR. Data including demographics, intraoperative BP, HR and OCR development were noted and analysed with SPSS version 22.

RESULTS: The total number of patients were 124, 62 in each group with a mean age of 9.45±1.61. Sixty-six (53.22%) patients were males and 58 (46.87%) patients were females. At 10-, 20- and 30-minutes interval, the SBP and DBP has no significant difference. At 10, 20, 30 minutes interval, the HR differed significantly (79.33±7.36 vs 66.65±6.83 (p˂0.05), 79.78±7.63 vs 66.57±7.06 (p˂0.05), 79.80±7.78 vs 66.52±7.01 (p˂0.05), respectively. Intraoperative OCR was recorded in 13 (21%) patients in sub-tenon’s (Group A) versus 56 (90.30%) patients in placebo (Group B) with statistically significant difference between the two (p<0.05).

CONCLUSION: Sub-tenon’s injection of bupivacaine reduces the incidence of Bradycardia and OCR in squint surgery patients after general anaesthesia induction and usage is recommended in routine.

PMID:36849367 | DOI:10.55519/JAMC-01-11512

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Phase-sensitive detection of anomalous diffusion dynamics in the neuronal membrane induced by ion channel gating

Phys Med Biol. 2023 Feb 27. doi: 10.1088/1361-6560/acbf9c. Online ahead of print.

ABSTRACT

Non-ergodicity of neuronal dynamics from rapid ion channel gating through the membrane induces membrane displacement statistics that deviate from Brownian motion. The membrane dynamics from ion channel gating were imaged by phase-sensitive optical coherence microscopy. The distribution of optical displacements of the neuronal membrane showed a Lévy-like distribution and the memory effect of the membrane dynamics by the ionic gating was estimated. The alternation of the correlation time was observed when neurons were exposed to channel-blocking molecules. Non-invasive optophysiology by detecting the anomalous diffusion characteristics of dynamic images is demonstrated.

PMID:36848681 | DOI:10.1088/1361-6560/acbf9c

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A feasibility study of enhanced prompt gamma imaging for range verification in proton therapy using deep learning

Phys Med Biol. 2023 Feb 27. doi: 10.1088/1361-6560/acbf9a. Online ahead of print.

ABSTRACT

Range uncertainty is a major concern affecting delivery precision in proton therapy. The Compton camera (CC)-based prompt-gamma (PG) imaging is a promising technique to provide 3D in-vivo range verification. However, conventional back-projected PG images suffer from severe distortions due to the limited view of CC, significantly limiting its clinical utility. Deep learning has demonstrated effectiveness in enhancing medical images from limited-view measurements. But different from other medical images with abundant anatomical structures, PGs emitted from a proton pencil beam take up an extremely low portion of the 3D image space, presenting both the attention and the imbalance challenge for deep learning. To solve these issues, we proposed a two-tier deep learning-based method with a novel weighted axis-projection loss to generate precise 3D PG images for proton range verification. This method consists of two models: first, a localization model is trained to define a region-of-interest (ROI) in the distorted back-projected PG image that contains the proton pencil beam; second, an enhancement model is trained to restore the true PG emissions with ROI attention. In this study, we simulated proton pencil beams delivered at clinical dose rates and levels in a tissue-equivalent phantom using Monte-Carlo (MC). PG detection with a CC was simulated using the MC-Plus-Detector-Effects model. Images were reconstructed using kernel-weighted-back-projection algorithm, and were then enhanced by the proposed method. Results demonstrated that the method effectively restored the 3D shape of PGs with proton pencil beam range clearly visible in all testing cases. Range errors were within 2 pixels (4 mm) in all directions in most cases at a dose level of 10^9 protons/beam. The method is fully automatic and nearly real-time. Overall, the preliminary study demonstrated the feasibility of the proposed method to generate accurate 3D PG images, providing a powerful tool for high-precision in-vivo range verification of proton therapy.

PMID:36848674 | DOI:10.1088/1361-6560/acbf9a

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Old Meets New: Mass Spectrometry-Based Untargeted Metabolomics Reveals Unusual Larvicidal Nitropropanoyl Glycosides from the Leaves of Heteropterys umbellata

J Nat Prod. 2023 Feb 27. doi: 10.1021/acs.jnatprod.2c00788. Online ahead of print.

ABSTRACT

The Aedes aegypti (Diptera: Culicidae) mosquito is the vector of several arboviruses in tropical and subtropical areas of the globe, and synthetic pesticides remain the most widely used combat strategy. This study describes the investigation of secondary metabolites with larvicidal activity from the Malpighiaceae taxon using a metabolomic and bioactivity-based approach. The workflow initially consisted of a larvicidal screening of 394 extracts from the leaves of 197 Malpighiaceae samples, which were extracted using solvents of different polarity, leading to the selection of Heteropterys umbellata for the identification of active compounds. By employing untargeted mass spectrometry-based metabolomics and multivariate analyses (PCA and PLS-DA), it was possible to determine that the metabolic profiles of different plant organs and collection sites differed significantly. A bioguided approach led to the isolation of isochlorogenic acid A (1) and the nitropropanoyl glucosides karakin (2) and 1,2,3,6-tetrakis-O-[3-nitropropanoyl]-beta-glucopyranose (3). These nitro compounds exhibited larvicidal activity, possibly potentialized by synergistic effects of their isomers in chromatographic fractions. Additionally, targeted quantification of the isolated compounds in different extracts corroborated the untargeted results from the statistical analyses. These results support a metabolomic-guided approach in combination with classical phytochemical techniques to search for natural larvicidal compounds for arboviral vector control.

PMID:36848642 | DOI:10.1021/acs.jnatprod.2c00788

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Validation of Predictive Analyses for Interim Decisions in Clinical Trials

JCO Precis Oncol. 2023 Feb;7:e2200606. doi: 10.1200/PO.22.00606.

ABSTRACT

PURPOSE: Adaptive clinical trials use algorithms to predict, during the study, patient outcomes and final study results. These predictions trigger interim decisions, such as early discontinuation of the trial, and can change the course of the study. Poor selection of the Prediction Analyses and Interim Decisions (PAID) plan in an adaptive clinical trial can have negative consequences, including the risk of exposing patients to ineffective or toxic treatments.

METHODS: We present an approach that leverages data sets from completed trials to evaluate and compare candidate PAIDs using interpretable validation metrics. The goal is to determine whether and how to incorporate predictions into major interim decisions in a clinical trial. Candidate PAIDs can differ in several aspects, such as the prediction models used, timing of interim analyses, and potential use of external data sets. To illustrate our approach, we considered a randomized clinical trial in glioblastoma. The study design includes interim futility analyses on the basis of the predictive probability that the final analysis, at the completion of the study, will provide significant evidence of treatment effects. We examined various PAIDs with different levels of complexity to investigate if the use of biomarkers, external data, or novel algorithms improved interim decisions in the glioblastoma clinical trial.

RESULTS: Validation analyses on the basis of completed trials and electronic health records support the selection of algorithms, predictive models, and other aspects of PAIDs for use in adaptive clinical trials. By contrast, PAID evaluations on the basis of arbitrarily defined ad hoc simulation scenarios, which are not tailored to previous clinical data and experience, tend to overvalue complex prediction procedures and produce poor estimates of trial operating characteristics such as power and the number of enrolled patients.

CONCLUSION: Validation analyses on the basis of completed trials and real world data support the selection of predictive models, interim analysis rules, and other aspects of PAIDs in future clinical trials.

PMID:36848613 | DOI:10.1200/PO.22.00606

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Prognostic Significance of Tumor-Infiltrating Lymphocytes Determined Using LinkNet on Colorectal Cancer Pathology Images

JCO Precis Oncol. 2023 Feb;7:e2200522. doi: 10.1200/PO.22.00522.

ABSTRACT

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have a significant prognostic value in cancers. However, very few automated, deep learning-based TIL scoring algorithms have been developed for colorectal cancer (CRC).

MATERIALS AND METHODS: We developed an automated, multiscale LinkNet workflow for quantifying TILs at the cellular level in CRC tumors using H&E-stained images from the Lizard data set with annotations of lymphocytes. The predictive performance of the automatic TIL scores (TILsLink) for disease progression and overall survival (OS) was evaluated using two international data sets, including 554 patients with CRC from The Cancer Genome Atlas (TCGA) and 1,130 patients with CRC from Molecular and Cellular Oncology (MCO).

RESULTS: The LinkNet model provided outstanding precision (0.9508), recall (0.9185), and overall F1 score (0.9347). Clear continuous TIL-hazard relationships were observed between TILsLink and the risk of disease progression or death in both TCGA and MCO cohorts. Both univariate and multivariate Cox regression analyses for the TCGA data demonstrated that patients with high TIL abundance had a significant (approximately 75%) reduction in risk for disease progression. In both the MCO and TCGA cohorts, the TIL-high group was significantly associated with improved OS in univariate analysis (30% and 54% reduction in risk, respectively). The favorable effects of high TIL levels were consistently observed in different subgroups (classified according to known risk factors).

CONCLUSION: The proposed deep-learning workflow for automatic TIL quantification on the basis of LinkNet can be a useful tool for CRC. TILsLink is likely an independent risk factor for disease progression and carries predictive information of disease progression beyond the current clinical risk factors and biomarkers. The prognostic significance of TILsLink for OS is also evident.

PMID:36848612 | DOI:10.1200/PO.22.00522

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Advancing interdisciplinary science for disrupting wildlife trafficking networks

Proc Natl Acad Sci U S A. 2023 Mar 7;120(10):e2208268120. doi: 10.1073/pnas.2208268120. Epub 2023 Feb 27.

ABSTRACT

Wildlife trafficking, whether local or transnational in scope, undermines sustainable development efforts, degrades cultural resources, endangers species, erodes the local and global economy, and facilitates the spread of zoonotic diseases. Wildlife trafficking networks (WTNs) occupy a unique gray space in supply chains-straddling licit and illicit networks, supporting legitimate and criminal workforces, and often demonstrating high resilience in their sourcing flexibility and adaptability. Authorities in different sectors desire, but frequently lack knowledge about how to allocate resources to disrupt illicit wildlife supply networks and prevent negative collateral impacts. Novel conceptualizations and a deeper scientific understanding of WTN structures are needed to help unravel the dynamics of interaction between disruption and resilience while accommodating socioenvironmental context. We use the case of ploughshare tortoise trafficking to help illustrate the potential of key advancements in interdisciplinary thinking. Insights herein suggest a significant need and opportunity for scientists to generate new science-based recommendations for WTN-related data collection and analysis for supply chain visibility, shifts in illicit supply chain dominance, network resilience, or limits of the supplier base.

PMID:36848572 | DOI:10.1073/pnas.2208268120