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.

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.

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.

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.

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.

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.

Anti-COVID property of subcutaneous ivermectin in synergy with zinc among midlife moderately symptomatic patients: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The study objective is to quantify the effectiveness of ivermectin (subcutaneous/oral IVM) in the presence or absence of zinc (Zn) for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients with moderate severity. TRIAL DESIGN: This quadruple-blinded, placebo-controlled randomized clinical trial will be a multiarmed multi-centered study with superiority framework. PARTICIPANTS: Quinquagenarian and sexagenarian patients with moderate COVID-19 symptoms and positive severe respiratory syndrome coronavirus -2 (SARS-CoV-2) PCR will be included. Participants with co-morbidities and pregnant women will be excluded. Patient recruitment will be done in Shaikh Zayed Medical Complex, Doctors Lounge and Ali Clinic in Lahore (Pakistan). INTERVENTION AND COMPARATOR: The registered patients will be allocated in 6 groups (30 participants each). Patients will be taking subcutaneous IVM at 200 µg/kg/48 h (Arm A) or subcutaneous IVM at 200 µg/kg/48 h and oral Zn 20mg/8 h (Arm B) or oral IVM at 0.2 mg/kg/day (Arm C) or oral IVM at 0.2 mg/kg/day and oral Zn 20mg/8 h (Arm D) or alone oral Zn 20mg/8 h (Arm E) or placebo alone (Arm X). Patients in all arms will receive standard care and respective placebo (empty capsule 8 hourly and/or subcutaneous normal saline 2ml/48 h). MAIN OUTCOMES: Primary endpoints will be duration of symptomatic phase and SARS-CoV-2 clearance along with high resolution CT (HRCT) chest score and clinical grade scale (CGS) on day 6. 30-day mortality will be documented as a secondary endpoint. SARS-CoV-2 clearance will be calculated by second PCR on day 7. HRCT chest score will be measured by the percentage and lung lobes involvement on day 6 with a maximum score of 25. CGS will be recorded on a seven-point scale; grade 1 (not hospitalized, no evidence of infection and resumption of normal activities), grade 2 (not hospitalized, but unable to resume normal activities), grade 3 (hospitalized, not requiring supplemental oxygen), grade 4 (hospitalized, requiring supplemental oxygen), grade 5 (hospitalized, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation), grade 6 (hospitalized, requiring ECMO and/or invasive mechanical ventilation) and grade 7 (death). RANDOMISATION: A simple lottery method will be used to randomly allocate scrutinized patients in 1:1:1:1:1:1 ratio in 6 groups. BLINDING (MASKING): Patients, primary care physicians, outcome assessors and the data collection team will be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 180 participants will be randomized into six arms with five investigational and one placebo group. TRIAL STATUS: Institutional Review Board Shaikh Zayed Post-Graduate Medical Complex, Lahore, Pakistan has approved the protocol (version 2.3) with ID SZMC/IRB/Internal0056/2020. The trial was approved on July 14, 2020, and enrolment started on July 30, 2020. The estimated completion date is October 30, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04472585 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.

Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. TRIAL DESIGN: The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. PARTICIPANTS: All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). INTERVENTION AND COMPARATOR: In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. RANDOMISATION: Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. BLINDING (MASKING): Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 1000 participants will be enrolled in the study with 1:1 allocation. TRIAL STATUS: The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. TRIAL REGISTRATION: Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 . 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.

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.

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.

Therapeutic efficacy of Honey and Nigella sativa against COVID-19: A multi-center randomized controlled clinical trial (HNS-COVID-PK)

BACKGROUNDNo definitive treatment exists for Coronavirus Disease 2019 (COVID-19). Honey and Nigella sativa (HNS) have established antiviral, antibacterial, anti-inflammatory and immunomodulatory properties. Hence, we investigated efficacy of HNS against COVID-19. wide METHODSWe conducted a multicenter, placebo-controlled, randomized clinical trial at 4 centers in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the study. Patients presenting with multi-organ failure, ventilator support, and chronic diseases (except diabetes mellitus and hypertension) were excluded. Patients were randomly assigned in 1:1 ratio to receive either honey (1 gm/Kg/day) and Nigella sativa seeds (80 mg/Kg/day) or placebo up-to 13 days along with standard care. The outcomes included symptom alleviation, viral clearance, and a 30-day mortality in intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT04347382. RESULTSThree hundred and thirteen patients - 210 moderate and 103 severe - underwent randomization from April 30 to July 29, 2020. Among these, 107 were assigned to HNS whereas 103 to placebo for moderate cases. For severe cases, 50 were given HNS and 53 were given placebos. HNS resulted in [~]50% reduction in time taken to alleviate symptoms as compared to placebo (Moderate (4 versus 7 days), Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, P<0.0001 and severe (6 versus 13 days) HR: 4.04; 95% CI, 2.46-6.64, P<0.0001). HNS also cleared the virus 4 days earlier than placebo group in moderate (6 versus 10 days, HR: 5.53; 95% CI: 3.76-8.14, P<0.0001) and severe cases (8.5 versus 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% versus 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, mortality rate was four-fold lower in HNS group than placebo (4% versus 18.87%, OR: 0.18; 95% CI: 0.02-0.92, P=0.029). No HNS-related adverse effects were observed. CONCLUSIONHNS significantly improved symptoms, viral clearance and mortality in COVID-19 patients. Thus, HNS represents an affordable over the counter therapy and can either be used alone or in combination with other treatments to achieve potentiating effects against COVID-19. FUNDINGFunded by Smile Welfare Organization, Shaikh Zayed Medical Complex, and Services Institute of Medical Sciences.

Trajectory of Risk-Standardized Survival Rates for In-Hospital Cardiac Arrest.

BACKGROUND: A hospital's risk-standardized survival rate (RSSR) for in-hospital cardiac arrest has emerged as an important metric to benchmark and incentivize hospital resuscitation quality. We examined whether hospital performance on the RSSR metric was stable or dynamic year-over-year and whether low-performing hospitals were able to improve survival outcomes over time. METHODS AND RESULTS: We used data from 84 089 adult patients with an in-hospital cardiac arrest from 166 hospitals with continuous participation in Get With The Guidelines-Resuscitation from 2012 to 2017. A 2-level hierarchical regression model was used to compute RSSRs during a baseline (2012-2013) and two follow-up periods (2014-2015 and 2016-2017). At baseline, hospitals were classified as top-, middle-, and bottom-performing if they ranked in the top 25%, middle 50%, and bottom 25%, respectively, on their RSSR metric during 2012 to 2013. We compared hospital performance on RSSR during follow-up between top, middle, and bottom-performing hospitals' at baseline. During 2012 to 2013, 42 hospitals were identified as top-performing (median RSSR, 31.7%), 82 as middle-performing (median RSSR, 24.6%), and 42 as bottom-performing (median RSSR, 18.7%). During both follow-up periods, >70% of top-performing hospitals ranked in the top 50%, a substantial proportion remained in the top 25% of RSSR during 2014 to 2015 (54.6%) and 2016 to 2017 (40.4%) follow-up periods. Likewise, nearly 75% of bottom-performing hospitals remained in the bottom 50% during both follow-up periods, with 50.0% in the bottom 25% of RSSR during 2014 to 2015 and 40.5% in the bottom 25% during 2016 to 2017. While percentile rankings were generally consistent over time at ≈45% of study hospitals, ≈1 in 5 (21.4%) bottom-performing hospitals showed large improvement in percentile rankings over time and a similar proportion (23.7%) of top-performing hospitals showed large decline in percentile rankings compared with baseline. CONCLUSIONS: Hospital performance on RSSR during baseline period was generally consistent over 4 years of follow-up. However, 1 in 5 bottom-performing hospitals had large improvement in survival over time. Identifying care and quality improvement innovations at these sites may provide opportunities to improve in-hospital cardiac arrest care at other hospitals.

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.

Design and Investigation of Modern UWB-MIMO Antenna with Optimized Isolation.

This paper proposes a compact, semi-circular shaped multiple input multiple output (MIMO) antenna design with high isolation and enhanced bandwidth for ultrawide band (UWB) applications. A decoupling stub is used for high isolation reaching up to -55 dB over the entire bandwidth. The proposed antenna is used for UWB as well as super wide band (SWB) applications. The overall size of the proposed antenna is 18 × 36 × 1.6   mm3. The | S 11 |   and voltage standing wave ratio (VSWR) of the proposed antenna are less than -10 dB and 2, respectively, in the range of 3-40 GHz. The total impedance bandwidth of the proposed design is 37 GHz. The VSWR, | S 11 | , | S 22 | , | S 21 | , | S 12 | , gain, envelope correlation coefficient (ECC), radiation pattern, and various other characteristic parameters are discussed in detail. The proposed antenna is optimized and simulated in a computer simulation technology (CST) studio, and printed on a FR4 substrate.

Mediastinal bronchial artery aneurysm with short inflow segment successfully treated with a patent ductus arteriosus occluder device.

Bronchial artery aneurysm (BAA) is a rare vascular abnormality that may result in life-threatening bleeding if it is left untreated. We present the case of a 35-year-old man with a mediastinal BAA characterized by a short inflow artery segment and tortuous single outflow vessel. The patient's BAA was treated with a novel approach involving placement of a patent ductus arteriosus closure device in the short inflow segment as well as coil embolization of the outflow vessel, successfully excluding the BAA. Two-week follow-up revealed no flow in the embolized artery on computed tomography angiography. This case demonstrates the first successful use of a patent ductus arteriosus occluder device in the treatment of a mediastinal BAA with short inflow segment.

Trends in Hospitalization, Management, and Clinical Outcomes Among Veterans With Critical Limb Ischemia.

BACKGROUND: Contemporary patterns in management and outcomes of critical limb ischemia among United States veterans are unknown. METHODS: We used Veterans Health Administration data to identify patients admitted for critical limb ischemia between 2005 and 2014. We examined temporal trends in incidence, management, and outcomes. RESULTS: A total of 20 938 veterans with critical limb ischemia were hospitalized between 2005 and 2014. Mean age was 67.8 years. Incidence decreased from 0.3 to 0.24 per 1000 persons from 2005 to 2013, P<0.01. During the study period, there was a temporal increase in use of revascularization within 90 days of hospitalization-endovascular (11.2% in 2005 to 18.4% in 2014), surgical (23.8% in 2005 to 26.4% in 2014), and hybrid (6.2% in 2005 to 13.1% in 2014, P value for trend <0.01). Statin prescriptions increased from 47.4% in 2005 to 60.9% in 2014 (P value for trend <0.01). There was a significant decline in risk-adjusted mortality (11.8% in 2005 to 9.7% in 2014) and major amputation (19.8% in 2005 to 12.9% in 2014; P value for trend <0.01 for both) at 90 days. In adjusted analyses, revascularization was associated with a lower risk of mortality (RR, 0.45 [95% CI, 0.41-0.50]; P<0.001) and major amputation at 90 days (RR, 0.23 [95% CI, 0.21-0.26]; P<0.001). Nearly half of the patients who underwent amputation did not receive an invasive vascular procedure within the preceding 90 days. There was large site-level variation in the use of revascularization (median rate, 41.7% [interquartile range, 12.5%-53.2%]). Differences in patient case-mix explained only 8% of site-level variation in receipt of revascularization. CONCLUSIONS: Over the past decade, use of revascularization increased among veterans with critical limb ischemia, which was accompanied by a reduction in mortality and major amputation. However, opportunities to further improve care in this high-risk population still remain.