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.

Lead Cap Use in Interventional Cardiology: Time to Protect Our Head in the Cardiac Catheterisation Laboratory?

Background: Radiation exposure is an occupational hazard for interventional cardiologists and cardiac catheterisation laboratory staff that can manifest with serious long-term health consequences. Personal protective equipment, including lead jackets and glasses, is common, but the use of radiation protective lead caps is inconsistent. Methods: A systematic review qualitative assessment of five observational studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines protocol was performed. Results: It was concluded that lead caps significantly reduce radiation exposure to the head, even when a ceiling-mounted lead shield was present. Conclusion: Although newer protective systems are being studied and introduced, tools, such as lead caps, need to be strongly considered and employed in the catheterisation laboratory as mainstay personal protective equipment.

In-Hospital Outcomes of COVID-19 Associated Myocarditis (from a Nationwide Inpatient Sample Database Study).

The prevalence of COVID-19 infection-related myocarditis, its in-hospital cardiovascular outcomes, and its impact on hospital cost and stay at national level are not well studied in the literature. The Nationwide Inpatient Sample Database from 2020 was queried to identify patients with COVID-19 and myocarditis versus those without myocarditis. Cardiovascular outcomes and resource utilization were studied among cohorts with COVID-19, with and without myocarditis, using descriptive statistics, multivariate regression matching, and propensity score matching using STATA version 17. Of 1,678,995 patients, 3,565 (0.21%) had COVID-19 with myocarditis, and 1,675,355 (99.78%) had COVID-19 without myocarditis. On multivariate regression analysis, we found higher odds of in-hospital mortality (adjusted odds ratio [aOR] 1.59, 95% confidence interval [CI] 1.27 to 1.9) in patients with myocarditis than in those without myocarditis, in addition to higher odds of major adverse cardiovascular and cerebrovascular events (aOR 3.54, 95% CI 2.8 to 4.4), acute kidney injury (aOR 1.29, 95% CI 1.27 to 1.9), heart failure (aOR 2.77, 95% CI 2.3 to 3.4), cardiogenic shock (aOR 10.2, 95% CI 7.9 to 13), myocardial infarction (aOR 5.74, 95% CI 4.5 to 7.3), and use of mechanical circulatory support (aOR 2.81, 95% CI 1.6 to 4.9). The propensity-matched cohort also favored similar outcomes. In conclusion, patients with COVID-19 and myocarditis had worse clinical outcomes, having a higher rate of in-hospital mortality, major adverse cardiovascular and cerebrovascular events with longer length of hospital stay, and higher hospitalization costs. Large prospective trials are necessary to validate these findings with diagnostic measures, including biopsy and cardiac magnetic resonance imaging for the extent of myocardial involvement.

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.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL): A Rare Cause of Transient Ischemic Attack.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited and autosomal dominant arteriopathy of the cerebral vasculature, which is commonly misdiagnosed due to its different modes of presentation. It is characterized by variable manifestations of ischemic episodes, migraine with aura, cognitive deficits, and psychiatric disturbances. CADASIL is caused by a genetic mutation in the NOTCH3 gene, which is present on chromosome 19. The diagnosis of CADASIL can be made by personal and family history, skin biopsy, and magnetic resonance imaging (MRI) of the head showing high-intensity signal lesions, microbleeds, and white matter changes. There are currently no disease-modifying therapies available for CADASIL, and management focuses on reducing risk factors such as diabetes and hypertension and control of symptoms. We present a rare cause of transient ischemic attack (TIA) in a young female who was later diagnosed with CADASIL and aim to highlight rare and inherited causes of TIA and strokes in younger patients.

Draft Genome Sequences and Antimicrobial Resistance Genes of Five Staphylococcus aureus Strains Isolated from Bovine Milk.

Staphylococcus aureus is one of the most important bacterial pathogens causing bovine mastitis, which leads to huge economic losses worldwide. Here, we report draft genome sequences and antimicrobial resistance gene profiles of five Staphylococcus aureus strains that were isolated from bovine milk in Pakistan.

Malaria Detection Accelerated: Combing a High-Throughput NanoZoomer Platform with a ParasiteMacro Algorithm.

Eradication of malaria, a mosquito-borne parasitic disease that hijacks human red blood cells, is a global priority. Microscopy remains the gold standard hallmark for diagnosis and estimation of parasitemia for malaria, to date. However, this approach is time-consuming and requires much expertise especially in malaria-endemic countries or in areas with low-density malaria infection. Thus, there is a need for accurate malaria diagnosis/parasitemia estimation with standardized, fast, and more reliable methods. To this end, we performed a proof-of-concept study using the automated imaging (NanoZoomer) platform to detect the malarial parasite in infected blood. The approach can be used as a steppingstone for malaria diagnosis and parasitemia estimation. Additionally, we created an algorithm (ParasiteMacro) compatible with free online imaging software (ImageJ) that can be used with low magnification objectives (e.g., 5×, 10×, and 20×) both in the NanoZoomer and routine microscope. The novel approach to estimate malarial parasitemia based on modern technologies compared to manual light microscopy demonstrated 100% sensitivity, 87% specificity, a 100% negative predictive value (NPV) and a 93% positive predictive value (PPV). The manual and automated malaria counts showed a good Pearson correlation for low- (R2 = 0.9377, r = 0.9683 and p < 0.0001) as well as high- parasitemia (R2 = 0.8170, r = 0.9044 and p < 0.0001) with low estimation errors. Our robust strategy that identifies and quantifies malaria can play a pivotal role in disease control strategies.

Dietary Component-Induced Inflammation and Its Amelioration by Prebiotics, Probiotics, and Synbiotics.

A balanced diet with many dietary components maintains immune homeostasis directly by interacting with innate and adaptive immune components or indirectly through gut microbiota and their metabolites. Dietary components may inhibit pro-inflammatory mediators and promote anti-inflammatory functions or vice versa. Western diets with imbalanced dietary components skew the immune balance toward pro-inflammation and induce intestinal inflammation, consequently leading to many intestinal and systemic inflammatory diseases like ulcerative colitis, Crohn's disease, irritable bowel syndrome, cardiovascular problems, obesity, and diabetes. The dietary component-induced inflammation is usually chronic in nature and frequently caused or accompanied by alterations in gut microbiota. Therefore, microbiome-targeted therapies such as probiotics, prebiotics and synbiotics hold great potentials to amend immune dysregulation and gut dysbiosis, preventing and treating intestinal and systemic inflammatory diseases. Probiotics, prebiotics and synbioitcs are progressively being added to foods and beverages, with claims of health benefits. However, the underlining mechanisms of these interventions for preventing and treating dietary component-induced inflammation are still not very clear. In addition, possibly ineffective or negative consequences of some probiotics, prebiotics and synbiotics call for stringent testing and regulation. Here, we will first briefly review inflammation, in terms of its types and the relationship between different dietary components and immune responses. Then, we focus on current knowledge about the direct and indirect effects of probiotics, prebiotics and synbiotics on intestinal and systemic inflammation. Understanding how probiotics, prebiotics and synbiotics modulate the immune system and gut microbiota will improve our strategies for preventing and treating dietary component-induced intestinal inflammation and inflammatory diseases.

Neocosmospora rubicola, a stem rot disease in potato: Characterization, distribution and management.

Potato (Solanum tuberosum L.) is one of the most important crops in maintaining global food security. Plant stand and yield are affected by production technology, climate, soil type, and biotic factors such as insects and diseases. Numerous fungal diseases including Neocosmospora rubicola, causing stem rot, are known to have negative effects on potato growth and yield quality. The pathogen is known to stunt growth and cause leaf yellowing with grayish-black stems. The infectivity of N. rubicola across a number of crops indicates the need to search for appropriate management approaches. Synthetic pesticides application is a major method to mitigate almost all potato diseases at this time. However, these pesticides significantly contribute to environmental damage and continuous use leads to pesticide resistance by pathogens. Consumers interest in organic products have influenced agronomists to shift toward the use of biologicals in controlling most pathogens, including N. rubicola. This review is an initial effort to carefully examine current and alternative approaches to control N. rubicola that are both environmentally safe and ecologically sound. Therefore, this review aims to draw attention to the N. rubicola distribution and symptomatology, and sustainable management strategies for potato stem rot disease. Applications of plant growth promoting bacteria (PGPB) as bioformulations with synthetic fertilizers have the potential to increase the tuber yield in both healthy and N. rubicola infested soils. Phosphorus and nitrogen applications along with the PGPB can improve plants uptake efficiency and reduce infestation of pathogen leading to increased yield. Therefore, to control N. rubicola infestation, with maximum tuber yield benefits, a pre-application of the biofertilizer is shown as a better option, based on the most recent studies. With the current limited information on the disease, precise screening of the available resistant potato cultivars, developing molecular markers for resistance genes against N. rubicola will assist to reduce spread and virulence of the pathogen.

A Case of Atypical Hemolytic Uremic Syndrome in a Pregnant Patient.

Atypical hemolytic uremic syndrome (HUS) is a rare but severe form of thrombotic microangiopathies (TMAs) that affects both children and adults. The clinical presentation is usually nonspecific, including a broad spectrum of symptoms ranging from abdominal pain, confusion, diarrhea, fatigue, irritability, hypertension, and lethargy. We present a case of a 36-year-old woman with medical comorbidities of asthma and pulmonary embolism who presented to our hospital in the 36th week of her pregnancy for preterm premature rupture of the membranes. The postoperative course was complicated with a sudden onset drop in hemoglobin and acute onset thrombocytopenia. Complements levels were normal while ADAMTS 13 (von Willebrand factor-cleaving protease) activity was 81% which ruled out ADAMTS 13 deficiency. No significant clinical improvement was seen after five cycles of plasmapheresis. She was later started on Eculizumab biweekly with marked improvement in biochemical and clinical status. Prompt diagnosis and treatment of atypical HUS are crucial as the prognosis is poor if untreated. The diagnosis of atypical HUS can be challenging as the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury can be seen in all thrombotic microangiopathies, thus careful clinical and laboratory assessment is required to establish the diagnosis. The new treatment modality, Eculizumab, the anti-complement monoclonal antibody, has become the first-line therapy for treating atypical HUS.

Proteomic Comparison of Ivermectin Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals Key Efflux Pumps as Possible Resistance Determinants.

Ivermectin (IVM) is a versatile drug used against many microorganisms. Staphylococcus aureus is one of the most devastating microorganisms. IVM sensitive and resistant S. aureus strains were recently reported. However, the underlying molecular mechanisms of resistance are unknown. Clinical isolates of S. aureus were used for determination of the sensitivities against IVM by growth curve analysis and time-kill kinetics. Then, proteomic, and biochemical approaches were applied to investigate the possible mechanisms of resistance. Proteomic results showed a total of 1849 proteins in the dataset for both strains, 425 unique proteins in strain O9 (IVM sensitive), and 354 unique proteins in strain O20 (IVM resistant). Eight proteins with transport functions were differentially expressed in the IVM resistant strain. Among them, three efflux pumps (mepA, emrB, and swrC) were confirmed by qPCR. The IVM resistant S. aureus may overexpress these proteins as a key resistance determinant. Further experiments are required to confirm the exact mechanistic relationship. Nevertheless, the possibility of blocking these transporters to reverse or delay the onset of resistance and reduce selection pressure is potentially appealing.

Vandetanib-Induced Hyponatremia and Torsades De Pointes: A Case Report.

Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the parafollicular cells of the thyroid gland. The prognosis is very poor in patients with advanced MTC. Vandetanib was approved for advanced MTC after randomized control trials showed that it had therapeutic efficacy and considerably prolonged progression-free survival. Vandetanib therapy is associated with serious cardiovascular side effects including hypertensive crisis and arrhythmias due to prolonged QTc. We present a case of an 83-year-old female with advanced metastatic MTC who is under treatment with vandetanib 300 mg/day and developed medication-related hyponatremia, QTc prolongation, ventricular fibrillation (VF), and torsades de pointes (TdP). Her vandetanib therapy was held. Subsequently, she did not show recurrences of TdP. This is the second such case report in the literature.

Evaluation of photosensitizer-containing superhydrophobic surfaces for the antibacterial treatment of periodontal biofilms.

Antimicrobial photodynamic therapy (aPDT) is a promising approach to control biofilms involved in periodontal diseases. However, certain challenges, such as staining of teeth, preferential interaction of photosensitizer (PS) with Gram-positive versus Gram-negative bacteria, and insufficient oxygen in hypoxic periodontal pockets have presented barriers to its use in the clinic. To overcome these challenges, a novel superhydrophobic (SH) film that generates airborne singlet oxygen has been developed. The SH-aPDT approach isolates the PS onto a topologically rough solid SH film on which channels allow air to diffuse to the PS surface, thus ensuring sufficient oxygen supply. Upon illumination, gas phase singlet oxygen (1O2) is produced and diffuses from the SH surface to the underlying biofilm. The killing efficacy was assessed as a function of transmitted fluence (17.9-89.5 J/cm2) and chorin e6 loading (96-1110 nmol/cm2) by counting of colony forming units, biofilm metabolism by XTT and confocal microscopy. The decrease in viability of both Gram-positive and Gram-negative bacteria in a multi-species biofilm was found to be linearly dependent on the fluence as well as the loading of the PS up to 71.6 J/cm2 when 1110 nmols/cm2 of chlorin e6 was used. A > 4.6 log bacterial reduction was observed under these conditions (p < 0.05). This novel SH-aPDT approach shows promise as an effective method to disinfect multi-species bacterial biofilms associated with periodontal disease and will be evaluated in animal models in future studies.

Metformin-Associated Lactic Acidosis: A Case Report and Review.

Metformin is widely prescribed as the first-line medication for type II diabetes mellitus. While the gastrointestinal side effects of metformin such as nausea, vomiting, diarrhea, and heartburn are quite common, one dangerous side effect of metformin, lactic acidosis, is extensively discussed yet rarely reported. Here, we discuss a 53-year-old female with type II diabetes mellitus who presented to an emergency department (ED) with chief complaints of dizziness and lightheadedness. The patient had chronic kidney disease (CKD) with a baseline estimated glomerular filtration rate (eGFR) of 45 mL/minute/1.73 m2. Initial laboratory results showed acute kidney injury (AKI) with hyperkalemia and lactic acidosis of 20 mmol/L. The patient was admitted to the ICU requiring emergent dialysis. Later, she was diagnosed with metformin-associated lactic acidosis (MALA). Her AKI and lactic acidosis subsequently improved. Metformin-associated lactic acidosis (MALA) is a rare but serious side effect of metformin. It is primarily reported in patients with chronic renal failure; therefore, it should be used with caution in these patients. Renal replacement therapy (RRT) is the critical management option for patients with MALA. Because of this, physicians prescribing metformin should carefully monitor all patients and assess the risk of developing severe side effects.

Current methods for the detection of Plasmodium parasite species infecting humans.

Malaria is the world's fatal parasitic disease. The ability to quickly and accurately identify malaria infection in challenging environments is crucial to allow efficient administration of the best treatment regime for human patients. If those techniques are accessible and efficient, global detection of Plasmodium species will become more sensitive, allowing faster and more precise action to be taken for disease control strategies. Recent advances in technology have enhanced our ability to diagnose different species of Plasmodium parasites with greater sensitivity and specificity. This literature review provides a summary and discussion of the current methods for the diagnosis and identification of Plasmodium spp. in human blood samples. So far not a single method is precise, but advanced technologies give consistent identification of a Plasmodium infection in endemic regions. By using the power of the recent methods, we can provide a broader understanding of the multiplicity of infection and or transmission dynamics of Plasmodium spp. This will result in improved disease control strategies, better-informed policy, and effective treatment for malaria-positive patients.

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.

Colitis Induced by Colon-Cleansing Agent.

Constipation is one of the most common functional gastrointestinal disorders and affects 20% of the general population. Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract that affects the large intestine and is characterized by chronic abdominal pain and altered bowel habits. We report a case of a 35-year-old African American man with a past medical history of IBS who presented to the clinic with a chief complaint of abdominal pain and bloody diarrhea for 1 week. The patient stated that he used a colon-cleansing agent because of persistent constipation. Computed tomography scan of the patient's abdomen and pelvis with contrast was performed which showed diffuse contiguous segmental mural thickening and nodularity seen along the distal transverse, descending, and sigmoid colon. Colonoscopy showed moderate diffuse inflammation characterized by altered vascularity, erythema, and granularity from the rectum to the descending colon, and localized mild inflammation characterized by erythema was found at the ileocecal valve. The patient's clinical condition improved with symptomatic management over 10 days. Patients with IBS should be advised to restrain from using a colon-cleansing agent without advice from their primary doctor as it can lead to various complications.

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.

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.