Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multicenter placebo-controlled randomized clinical trial.

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID-19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo-controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg-1 day-1 ) and Nigella sativa seeds (80 mg kg-1 day-1 ) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30-day mortality in the intention-to-treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46-6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76-8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62-7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02-0.92, p = 0.029). No HNS-related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID-19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.

Metal-Based Ionic Liquids in Oxidative Desulfurization: A Critical Review.

Ionic liquids (ILs) as novel functional desulfurization materials have attracted increasing attentions. Metal-based ionic liquids (MILs) are classified into three types of metal chloride ILs, metal oxide ILs, and metal complex ILs based on the definition and basic structure of MILs in this critical review. On the basis of the properties of ILs such as structure designability, super dissolution performance, good thermal and chemical stability, nonflammability, and wide electrochemical window, MILs exhibit unique advantages on hydrophobicity, oxidation performance, and Brönsted-Lewis acidity. Therefore, MILs possess both the absorption and oxidation centers for the intramolecular adsorption and oxidation to improve the oxidative desulfurization (ODS) process. During the novel nonaqueous wet oxidative desulfurization process (Nasil), H2S can be oxidized into elemental sulfur with hydrophobic MILs, which can be regenerated by oxygen for recycle, to solve the problems of low sulfur capacity, low sulfur quality, and severe secondary pollution in the aqueous Lo-Cat wet oxidative desulfurization process. Another outstanding feature of MILs in ODS is biomimetic catalysis, which has the function of activating molecular oxygen and improving the oxidation performance. Metal oxide ILs and metal complex ILs are used in combination with hydrogen peroxide or oxygen with the existing water to generate a Fenton-like reaction to convert hydrophobic organic sulfur or SO2 into hydrophilic sulfoxide/sulfone or sulfur acid, respectively. However, the corrosion of Cl- to the equipment and emulsification phenomenon in the extraction process of sulfoxide/sulfone separation still need further study. Furthermore, the promising strategies to construct highly efficient and green desulfurization processes for large-scale applications are provided.

Closed-Loop Elastic Demand Control under Dynamic Pricing Program in Smart Microgrid Using Super Twisting Sliding Mode Controller.

Electricity demand is rising due to industrialisation, population growth and economic development. To meet this rising electricity demand, towns are renovated by smart cities, where the internet of things enabled devices, communication technologies, dynamic pricing servers and renewable energy sources are integrated. Internet of things (IoT) refers to scenarios where network connectivity and computing capability is extended to objects, sensors and other items not normally considered computers. IoT allows these devices to generate, exchange and consume data without or with minimum human intervention. This integrated environment of smart cities maintains a balance between demand and supply. In this work, we proposed a closed-loop super twisting sliding mode controller (STSMC) to handle the uncertain and fluctuating load to maintain the balance between demand and supply persistently. Demand-side load management (DSLM) consists of agents-based demand response (DR) programs that are designed to control, change and shift the load usage pattern according to the price of the energy of a smart grid community. In smart grids, evolved DR programs are implemented which facilitate controlling of consumer demand by effective regulation services. The DSLM under price-based DR programs perform load shifting, peak clipping and valley filling to maintain the balance between demand and supply. We demonstrate a theoretical control approach for persistent demand control by dynamic price-based closed-loop STSMC. A renewable energy integrated microgrid scenario is discussed numerically to show that the demand of consumers can be controlled through STSMC, which regulates the electricity price to the DSLM agents of the smart grid community. The overall demand elasticity of the current study is represented by a first-order dynamic price generation model having a piece-wise linear price-based DR program. The simulation environment for this whole scenario is developed in MATLAB/Simulink. The simulations validate that the closed-loop price-based elastic demand control technique can trace down the generation of a renewable energy integrated microgrid.

Conservative management of type 1A endoleaks at completion angiogram in endovascular repair of infra-renal abdominal aortic aneurysms with current generation stent grafts.

PURPOSE: Proximal type 1A endoleaks on completion intra-operative angiography are not infrequently seen following endovascular abdominal aneurysm repair (EVAR). The natural course of these leaks is not well established. We sought to determine the rate of spontaneous resolution and a conservative treatment approach to these endoleaks. METHODS: All cases involving endovascular repairs of infra-renal abdominal aortic aneurysms resulting in proximal type 1A endoleak on final intra-operative completion angiography were retrospectively reviewed from 1 April 2010 and 30 March 2015. Demographic, pre and post-procedural imaging, and clinical outcomes were reviewed. Summarizing descriptive statistics are reported. RESULTS: Of the 337 patients who underwent an EVAR, 24 patients (7.1%) had a proximal type 1A endoleak on final intra-operative angiography. Twenty-two of 24 patients (92%) with proximal type 1A endoleaks had spontaneous resolution on follow-up imaging without any intervention, while two (8%) patients had a persistent endoleak. One of these patients required intervention. The median follow-up for patients with resolved endoleaks was 2.5 years vs. 4 and 6 years, respectively, for patients that did not resolve spontaneously. CONCLUSION: A conservative approach may be used in the management of patients with proximal type 1A endoleaks on completion angiography once maximum proximal seal was achieved intra-operatively as the vast majority of these leaks spontaneously seal.

An Efficient Routing Protocol Based on Stretched Holding Time Difference for Underwater Wireless Sensor Networks.

Underwater Wireless Sensors Networks (UWSNs) use acoustic waves as a communication medium because of the high attenuation to radio and optical waves underwater. However, acoustic signals lack propagation speed as compared to radio or optical waves. In addition, the UWSNs also pose various intrinsic challenges, i.e., frequent node mobility with water currents, high error rate, low bandwidth, long delays, and energy scarcity. Various UWSN routing protocols have been proposed to overcome the above-mentioned challenges. Vector-based routing protocols confine the communication within a virtual pipeline for the sake of directionality and define a fixed pipeline radius between the source node and the centerline station. Energy-Scaled and Expanded Vector-Based Forwarding (ESEVBF) protocol limits the number of duplicate packets by expanding the holding time according to the propagation delay, and thus reduces the energy consumption via the remaining energy of Potential Forwarding Nodes (PFNs) at the first hop. The holding time mechanism of ESEVBF is restricted only to the first-hop PFNs of the source node. The protocol fails when there is a void or energy hole at the second hop, affecting the reliability of the system. Our proposed protocol, Extended Energy-Scaled and Expanded Vector-Based Forwarding Protocol (EESEVBF), exploits the holding time mechanism to suppress duplicate packets. Moreover, the proposed protocol tackles the hidden terminal problem due to which a reasonable reduction in duplicate packets initiated by the reproducing nodes occurs. The holding time is calculated based on the following four parameters: (i) the distance from the boundary of the transmission area relative to the PFNs' inverse energy at the 1st and 2nd hop, (ii) distance from the virtual pipeline, (iii) distance from the source to the PFN at the second hop, and (iv) distance from the first-hop PFN to its destination. Therefore, the proposed protocol stretches the holding time difference based on two hops, resulting in lower energy consumption, decreased end-to-end delay, and increased packet delivery ratio. The simulation results demonstrate that compared to ESEVBF, our proposed protocol EESEVBF experiences 20.2 % lesser delay, approximately 6.66 % more energy efficiency, and a further 11.26 % reduction in generating redundant packets.

DOW-PR DOlphin and Whale Pods Routing Protocol for Underwater Wireless Sensor Networks (UWSNs).

Underwater Wireless Sensor Networks (UWSNs) have intrinsic challenges that include long propagation delays, high mobility of sensor nodes due to water currents, Doppler spread, delay variance, multipath, attenuation and geometric spreading. The existing Weighting Depth and Forwarding Area Division Depth Based Routing (WDFAD-DBR) protocol considers the weighting depth of the two hops in order to select the next Potential Forwarding Node (PFN). To improve the performance of WDFAD-DBR, we propose DOlphin and Whale Pod Routing protocol (DOW-PR). In this scheme, we divide the transmission range into a number of transmission power levels and at the same time select the next PFNs from forwarding and suppressed zones. In contrast to WDFAD-DBR, our scheme not only considers the packet upward advancement, but also takes into account the number of suppressed nodes and number of PFNs at the first and second hops. Consequently, reasonable energy reduction is observed while receiving and transmitting packets. Moreover, our scheme also considers the hops count of the PFNs from the sink. In the absence of PFNs, the proposed scheme will select the node from the suppressed region for broadcasting and thus ensures minimum loss of data. Besides this, we also propose another routing scheme (whale pod) in which multiple sinks are placed at water surface, but one sink is embedded inside the water and is physically connected with the surface sink through high bandwidth connection. Simulation results show that the proposed scheme has high Packet Delivery Ratio (PDR), low energy tax, reduced Accumulated Propagation Distance (APD) and increased the network lifetime.

Resolution (and Late Recurrence) of WATCHMAN Device-Related Thrombus Following Treatment with Dabigatran.

The WATCHMAN left atrial (LA) appendage closure system is an alternative therapy for stroke prevention in patients with atrial fibrillation who are intolerant to chronic oral anticoagulation with warfarin. Infrequently, LA device-related thrombus (DRT) has been suspected. Optimal treatment of DRT is not known, and the efficacy of novel oral anticoagulants (NOAC) in this setting has not been previously described. A 69-year-old woman with permanent atrial fibrillation underwent WATCHMAN device placement. A transesophageal echocardiogram (TEE) performed 45 days following implant revealed a well-seated device. A 1-year follow-up TEE revealed a 1.2 × 0.8 cm sized DRT on the LA aspect of the WATCHMAN device. She was prescribed dabigatran 150 mg po BID for 3 months and she remained on aspirin 325 mg per day. She returned approximately 4 months later (and several weeks after completing her 3-month course of dabigatran) for a repeat TEE, which revealed complete resolution of the DRT. A TEE was performed approximately 8 months later and revealed a new DRT measuring 1 cm in diameter on the LA aspect of the device. This is the first report of successful WATCHMAN DRT treatment with a NOAC, and the first report of late DRT recurrence following treatment to resolution with an anticoagulant. This case report demonstrates that (1) WATCHMAN DRT may form late following implantation, (2) DRT resolution is possible with NOACs, specifically dabigatran, and (3) late recurrence of DRT is possible, even after treatment to initial resolution with systemic anticoagulation.

Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of Observational Studies.

Recent evidence, though conflicting, suggests an association between azithromycin use and cardiovascular death. We conducted a systematic review and meta-analysis to evaluate the effect of azithromycin on risk of death. Multiple databases were searched. Authors independently screened and extracted the data from studies. Primary outcome of interest was risk of death (cardiovascular and/or noncardiovascular). Subgroup analyses were conducted to explore the source of a possible heterogeneity. Random effects model meta-analysis and hazards ratio (HR) were used to pool the data and calculate the overall effect estimate, respectively. Eight hundred twenty-eight citations, identified with 5 cohort studies that involved 2,246,178 episodes of azithromycin use, met our inclusion criteria. Azithromycin use was not associated with higher risk of death from any cause, HR = 0.99 [confidence interval (CI), 0.82-1.19], I = 54%, or cardiovascular cause, HR = 1.15 (CI, 0.66-2.00), I = 64%, but there was a moderate degree of heterogeneity. Subgroup analyses have shown no increased risk of death with azithromycin use in younger population with zero degree of heterogeneity, HR = 0.85 (CI, 0.66-1.09), I = 0%. However, current use of azithromycin (within 1-5 days of therapy) was associated with a higher risk of death among older population with mild degree of heterogeneity, HR = 1.64 (CI, 1.23-2.19), I = 4%. In summary, azithromycin use was not associated with higher risk of death particularly in younger population. Nevertheless, older population might be at higher risk of death with current use of azithromycin, and an alternative therapy should probably be considered.

Thrombus Characteristics Are Related to Collaterals and Angioarchitecture in Acute Stroke.

BACKGROUND: We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA). METHODS: Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA. RESULTS: A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006). CONCLUSIONS: Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.

Factors Responsible for Worse Outcomes in STEMI Patients With Early vs Delayed Treatment Presenting in a Tertiary Care Center in a Third World Country.

The aim of the study is to compare the outcomes among ST-segment elevation myocardial infarction (STEMI) cases with early treatment vs delayed treatment. It was a prospective comparative study on 186 patients with consecutive (nonprobability) sampling. Two groups of cases were made as per their time to get admitted to the hospital (ie, within 2 hours of symptom onset = Group A; after 2 hours of symptom onset = Group B). Patients were asked for factors causing a delay in treatment after the onset of symptoms and were monitored for STEMI outcomes. The mean age of all patients was 46.62 ± 9.76 years and there were 140 (75.27%) male and 46 (24.73%) female, and male to female ratio 3:1.Factors significant for delayed treatment vs nondelayed treatment were poor social economic status (65.6% vs 20.4%), history of chronic stable angina (33.3% vs 11.8%), delayed response in the emergency room (20.4% vs 8.6%), delayed ECG acquisition (26.9% vs 8.6%), delayed ECG interpretation (25.8% vs 4.3%), pain at night 12:00-6:00 AM (21.5% vs 9.7%) and belief that the chest pain is noncardiac (26.9% vs 3.2%). Acute heart failure was significantly greater in group B (9.7%) in comparison with group A (2.2%), re-infarction was 18.3% in group B in comparison with 7.5% group A. Similarly sustained ventricular tachycardia and ventricular fibrillation and in-hospital mortality were higher in group B (12.9%, 14%, and 12.9% respectively). Due to delayed treatment patients had higher hospital stays, and complications, like acute heart failure, re-infarction, ventricular fibrillation, and in-hospital mortality.

Perfusion MR predicts outcome in high-risk transient ischemic attack/minor stroke: a derivation-validation study.

BACKGROUND AND PURPOSE: Transient or minor ischemic stroke is associated with an early risk of deterioration. Baseline perfusion-diffusion mismatch may predict clinical deterioration and infarct growth in this population. METHODS: High-risk transient ischemic attack and minor stroke (National Institutes of Health Stroke Scale ≤3) subjects were prospectively enrolled and imaged with MRI within 24 hours of symptom onset as part of sequential derivation and validation cohorts. Baseline diffusion-weighted imaging, perfusion-weighted imaging (Tmax≥4 s), mismatch (Tmax≥4 s-diffusion-weighted imaging), and follow-up fluid-attenuated inversion recovery infarct volumes were measured. Primary outcome was infarct growth on fluid-attenuated inversion recovery, and secondary outcome was symptom progression. RESULTS: One hundred thirty-seven and 281 subjects were included in the derivation and validation cohorts, respectively. Infarct growth occurred in 18.5% of the derivation and 5.5% of the validation cohorts. Symptom progression occurred in 9.5% of the derivation and 4.5% of the validation cohorts. In the derivation cohort, subjects with baseline mismatch were significantly more likely to show infarct growth on fluid-attenuated inversion recovery (relative risk [RR], 13.5; 95% confidence interval [CI], 4.2-38.9) and symptom progression (RR, 7.0; 95% CI, 2.0-7.3). A baseline mismatch volume of 10 mL in the derivation cohort was the optimal threshold to predict infarct growth (area under the curve, 0.89; 95% CI, 0.80-0.98). This threshold was highly predictive of infarct growth in the validation cohort (P=0.001). Baseline mismatch was associated with clinical deterioration in the derivation (area under the curve, 0.81; 95% CI, 0.67-0.96) and validation cohorts (area under the curve, 0.66; 95% CI, 0.46-0.85). CONCLUSIONS: Among subjects with high-risk transient ischemic attack and minor stroke, diffusion-weighted imaging-perfusion-weighted imaging mismatch predicts infarct growth and clinical deterioration. These findings suggest that reperfusion strategies would be beneficial in this population.

Sustainability-oriented innovation system and economic stability of the innovative countries.

Novelcoronavirus-19 has created a challenging situation for developed as well as developing countries to sustain economic stability. There are a lot of controversies for policymakers to formulate an effective policy for reviving economic stability and minimizing the economic effects of this pandemic. The present study focuses on the internal mechanism of the Sustainability Oriented Innovation System and its subsequent effects on economic stability in most innovative economies. For empirical analysis of the most innovative countries (12 countries) high-income, middle-income, low-income, and lower-middle-income countries are selected. The Sustainability Oriented Innovation System is represented through the innovation input index and innovation output index. Economic stability is measured through the GDP growth rate of respective countries. A set of panel data was developed for the period of 11 years and Fixed Effect Methods were used to ascertain the empirical findings. The outcomes indicate that innovation is the main force of economic stability. The study's results are important to policymakers to promote, stimulate and support economic stability through their strategies. Future studies may focus on the effects of the Sustainability Oriented Innovation System on economic stability in regional blocks like the EU, ASEAN, and G-20 countries.

General perceptions and practices of smokers regarding tobacco-related issues and hazards.

OBJECTIVE: To assess the perceptions and practices related to tobacco consumption and its hazards among cigarette smokers seeking medical attention. METHODS: The cross-sectional study included 180 active smokers who were either hospitalised in medical or chest ward or attending pulmonary OPD at Shaikh Zayed Hospital, Lahore, between January and July 2010. Patients having altered sensorium were excluded from the study. A questionnaire was filled by the consulting participants. SPSS version 15 and chi-square tests were used for statistical analyses. RESULTS: A total of 180 questionnaires were distributed among 118 (65.6%) in-house and 62 (34.4%) active smokers in the out-patients department. These included 154 (85.6%) males and 26 (14.4%) females, with a mean age of 53.84 +/- 17.35 years, and with varying pack years (mean 26.44 +/- 19.89). Apart from cigarettes, 42 (74%) were also smoking other types of tobacco. Attempt to quit smoking was made by 92 (51.1%) and 151 (83.9%) were willing to give up. Majority of them 130 (72%) had at least two more smokers in the family. Most of the patients 169 (93.9%) presented with illnesses directly related to smoking. Besides, 127 (70.6%) patients had visited their general practitioners within the preceding year and a positive history of hospitalisation was found in 101 (56.1%). Regarding the knowledge of smoking hazards, only 5 (2.8%) could name three organs that may dysfunction due to smoking. While 162 (90%) had poor perception regarding the estimated number of chemicals in a cigarette, 120 (66.7%) knew the smoking's association with cancer. CONCLUSION: A high proportion of urban population consumes tobacco and most are poorly informed about the traumatic effects of its consumption. The continuing habits of patients with a history of seeking medical attention suggest that healthcare providers are missing opportunities for quit-smoking counselling.

Meta-Analysis Comparing Drug-Coated Balloons and Percutaneous Transluminal Angioplasty for Infrapopliteal Artery Disease.

Limited data is available regarding the safety and effectiveness of drug-coated balloon (DCB) versus conventional percutaneous transluminal balloon angioplasty (PTA) in the treatment of critical limb ischemia because of infrapopliteal peripheral arterial disease. We conducted an updated meta-analysis to assess the safety and efficacy of DCB in the treatment of infrapopliteal disease. A database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through November 15, 2021. Randomized trials that compared DCB with conventional PTA in treating infrapopliteal arterial disease were included. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. A total of 9 trials were included (1,501 participants) in the study. The mean age was 71.1 ± 10.2 years. Regarding the primary end points, treating infrapopliteal arterial disease with DCB had a lower incidence of re-stenosis (RR 0.48, 95% CI 0.33 to 0.70, p = 0.0001) with no significant difference in all-cause mortality (RR 1.11, 95% CI 0.73 to 1.69, p = 0.61), compared with conventional PTA. With regards to the secondary end points, DCB usage was associated with a significant reduction in clinically driven target lesion revascularization (RR 0.54, 95% CI 0.35 to 0.84, p = 0.006) with no significant difference with regards to major target limb amputation and major adverse cardiovascular events (p ≥0.05). In conclusion, among patients with critical limb ischemia secondary to infrapopliteal artery disease, DCB usage was associated with a significantly lower number of restenosis and clinically driven target lesion revascularization compared with conventional PTA. There was no increase in all-cause mortality or major target limb amputation with the use of DCB.

Development of a radiomic signature for predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) improves overall survival, but pathological response rates are low. Predictive biomarkers could select those patients most likely to benefit from NAC. Radiomics technology offers a novel, non-invasive method to identify predictive biomarkers. Our study aimed to develop a predictive radiomics signature for response to NAC in MIBC. METHODS: An institutional bladder cancer database was used to identify MIBC patients who were treated with NAC followed by radical cystectomy. Patients were classified into responders and non-responders based on pathological response. Bladder lesions on computed tomography images taken prior to NAC were contoured. Extracted radiomics features were used to train a radial basis function support vector machine classifier to learn a prediction rule to distinguish responders from non-responders. The discriminative accuracy of the classifier was then tested using a nested 10-fold cross-validation protocol. RESULTS: Nineteen patients who underwent NAC followed by radical cystectomy were found to be eligible for analysis. Of these, nine (47%) patients were classified as responders and 10 (53%) as non-responders. Nineteen bladder lesions were contoured. The sensitivity, specificity, and discriminative accuracy were 52.9±9.4%, 69.4±8.6%, and 62.1±6.1%, respectively. This corresponded to an area under the curve of 0.63±0.08 (p=0.20). CONCLUSIONS: Our developed radiomics signature demonstrated modest discriminative accuracy; however, these results may have been influenced by small sample size and heterogeneity in image acquisition. Future research using novel methods for computer-based image analysis on a larger cohort of patients is warranted.

Ankle- and Toe-Brachial Index for Peripheral Artery Disease Identification: Unlocking Clinical Data Through Novel Methods.

BACKGROUND: Despite its high prevalence and clinical impact, research on peripheral artery disease (PAD) remains limited due to poor accuracy of billing codes. Ankle-brachial index (ABI) and toe-brachial index can be used to identify PAD patients with high accuracy within electronic health records. METHODS: We developed a novel natural language processing (NLP) algorithm for extracting ABI and toe-brachial index values and laterality (right or left) from ABI reports. A random sample of 800 reports from 94 Veterans Affairs facilities during 2015 to 2017 was selected and annotated by clinical experts. We trained the NLP system using random forest models and optimized it through sequential iterations of 10-fold cross-validation and error analysis on 600 test reports and evaluated its final performance on a separate set of 200 reports. We also assessed the accuracy of NLP-extracted ABI and toe-brachial index values for identifying patients with PAD in a separate cohort undergoing ABI testing. RESULTS: The NLP system had an overall precision (positive predictive value) of 0.85, recall (sensitivity) of 0.93, and F1 measure (accuracy) of 0.89 to correctly identify ABI/toe-brachial index values and laterality. Among 261 patients with ABI testing (49% PAD), the NLP system achieved a positive predictive value of 92.3%, sensitivity of 83.1%, and specificity of 93.1% to identify PAD when compared with a structured chart review. The above findings were consistent in a range of sensitivity analysis. CONCLUSIONS: We successfully developed and validated an NLP system for identifying patients with PAD within the Veterans Affairs electronic health record. Our findings have broad implications for PAD research and quality improvement.

Clinical efficacy of iodine complex in SARS-CoV-2-infected patients with mild to moderate symptoms: study protocol for a randomized controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus-infected millions globally. Despite a wide range of advised options for the treatment of COVID-19, a single strategy to tackle this pandemic remains elusive, thus far. That is why we are conducting a clinical trial to find out the efficacy of iodine complex to clear a viral load of severe respiratory syndrome coronavirus-2 (SARS-CoV-2) along with a reduction in time taken to alleviate symptoms. METHOD: The proposed study is a placebo-controlled, add-on, randomized trial using parallel group designs. This is a closed-label and adaptive with sample size reassessment, multi-centered design with a 1:1:1:1 allocation ratio and superiority framework. It will be conducted in Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic, and Doctors Lounge, Lahore, Pakistan. This study will have three arms of mild to moderately symptomatic COVID-19 patients (50 patients in each) which will receive ionic-iodine polymer complex with 200 mg of elemental iodine: interventional arm A will have encapsulated, arm B will receive suspension syrup form, arm C will get throat spray, while arm X will be standard care with placebo. Data will be collected on self-constructed, close-ended questionnaires after obtaining written consent. Data will be analyzed using SAS version 9.4. COVID-19 patients will be monitored by RT-PCR and HRCT (high-resolution computed tomography) chest. In addition to these, the duration of the symptomatic phase and mortality benefits will be analyzed in both groups. DISCUSSION: The study is designed to measure the superior efficacy of the iodine complex as an add-on in treating COVID-19-positive patients with mild to moderate symptoms. This combination is hypothesized to improve various parameters like rapid viral load reduction, clinical and radiological improvement, lower mortality, and reduction in hospitalization. The trial will aid in devising a better strategy to cope with COVID-19 in a relatively inexpensive and accessible way. The implications are global, and this could prove itself to be the most manageable intervention against COVID-19 especially for patients from limited-resource countries with deprived socioeconomic status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04473261 . Registered on July 16, 2020.

Knowledge, attitude, and practice of clinicians about antimicrobial stewardship and resistance among hospitals of Pakistan: a multicenter cross-sectional study.

Considering that antimicrobial resistance (AMR) is a global challenge, there is a dire need to assess the knowledge, attitude, and practice (KAP) of clinicians in AMR endemic countries. The current multicenter, cross-sectional study aimed at highlighting gaps in antimicrobial (AM) stewardship and AMR among practicing doctors working in public tertiary care teaching hospitals of Lahore, Pakistan. A KAP survey, based on a self-administered questionnaire containing 45 questions, was distributed among 336 clinicians in 6 randomly selected hospitals. Overall, 92% of the clinicians considered AMR as a worldwide problem but only 66% disagreed that cold and flu symptoms require antibiotics. Moreover, around 68% of the doctors felt confident about their practice in AM but still, 96% felt the need to get more knowledge about AM drugs. The need for refresher courses on rational antibiotic use was expressed by 84% of the participants. The main contributing factors considered for AMR by the doctors included excessive AM usage in the medical profession (87.1%) and multiple antibiotics per prescription (76.4%). Pharmacologically, AM spectrum was accurately chosen by 1.4% for Ampicillin, 0.003% for Erythromycin and 0% for Levofloxacin. Clinically, more than 50% of the clinicians used miscellaneous AM for empirical therapy of respiratory tract infection and cholecystitis. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 25. It is concluded that the knowledge of clinicians is relatively poor for AM spectrum and drugs of choice for certain infections. However, the clinicians are aware of their shortcomings and desire for improvement.

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan.

BACKGROUD: Due to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA). METHODS: A total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant. RESULTS: Out of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m2. We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed. CONCLUSIONS: Tibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.

A quadruple blinded placebo controlled randomised trial to evaluate the effectiveness of an Iodine complex for patients with mild to moderate COVID-19 in Pakistan (I-COVID-PK): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. TRIAL DESIGN: The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. PARTICIPANTS: All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. INTERVENTION AND COMPARATOR: In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. RANDOMISATION: Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. BLINDING (MASKING): This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study's Primary Investigator will have information about the arms and their interventions. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 200 patients will be randomized into four groups with three experimental and one placebo arm. TRIAL STATUS: Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.