Safety and immunogenicity of a recombinant receptor-binding domain-based protein subunit vaccine (Noora vaccine™) against COVID-19 in adults: A randomized, double-blind, placebo-controlled, Phase 1 trial.

The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID-19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor-binding domain (RBD)-based protein subunit vaccine (Noora vaccine) against COVID-19 in adults. This Phase 1 trial is a randomized, double-blind, placebo-controlled study to evaluate the safety and immunogenicity of the recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti-RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti-RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.

Topical sucralfate for treatment of mucocutaneous conditions: A systematic review on clinical evidences.

Sucralfate is an aluminum salt of sucrose octasulfate, generally considered safe in terms of adverse effects. Systemic sucralfate is FDA-approved for the treatment of duodenal ulcers. Since 1991, topical sucralfate has been used in various mucocutaneous conditions, but it is not approved by the FDA yet. In this systematic review, the online databases were searched with appropriate keywords, and the papers were screened by the authors. After screening steps, the relevant articles were selected according to the inclusions and exclusions criteria. Finally, the full texts of 18 articles were included for final evaluations. In conclusion, topical sucralfate has some clinical benefit in several mucocutaneous conditions, including mucocutaneous inflammatory conditions (e.g., post-radiotherapy reaction, diaper dermatitis, keratoconjunctivitis sicca, etc.), mucocutaneous infectious disorders (e.g., peristomal wound reaction/infection); ulcers; burns, and also pain relief.

Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality worldwide. The disease attacks the lung tissue and may lead to acute respiratory distress syndrome. An in vitro study showed that hydroxychloroquine (HCQ) has a prophylactic effect against COVID-19 due to its anti-inflammatory effects. The present study aimed to evaluate the prophylactic effect of HCQ on individuals in close contact with patients with COVID-19. METHOD: In this quasi-trial study, we prescribed HCQ for 7 days to all people who had close contact with a patient with COVID-19. All contacts underwent a nasal swab in two steps, and those positive for COVID-19 were excluded from the study. After 14 days of follow-up, the clinical and laboratory manifestations of COVID-19 were evaluated. RESULTS: A total of 113 participants completed the study. The HCQ group comprised 51 (45.13%) contacts, and 62 (54.86%) contacts were allocated to the control group. According to the results of clinical examination and real-time polymerase chain reaction test, 8 (12.90%) contacts in the control group were reported to have contracted COVID-19. In the HCQ group, 7 (13.72%) contacts were confirmed to have contracted COVID-19. There was no relationship between HCQ use and age, sex, underlying disorders, and laboratory data (all p > 0.05). In terms of HCQ side effects, five participants experienced gastrointestinal and cutaneous side effects that subsided on discontinuation of HCQ. CONCLUSION: The current study showed that HCQ had no prophylactic effect with regard to COVID-19 prevention.

Intravesical alprostadil as a promising agent in BK virus-associated hemorrhagic cystitis: A report of a refractory case.

Allogeneic stem cell transplant recipients are at risk of BK virus-associated hemorrhagic cystitis. This condition causes a significant morbidity and worsens clinical outcomes. The standard cares for BK virus-associated hemorrhagic cystitis are saline irrigation and forced diuresis. Notably, several beneficial roles are proposed for antiviral and anti-inflammatory agents against BK virus-associated hemorrhagic cystitis. However, cases who are at risk of cystectomy remain refractory. Herein, we present a 13-year-old boy with severe hematuria by passing two months from his allogeneic stem cell transplantation. The laboratory work up showed high BK viremia >1.1 ×  108 copies/ml in this case's urine sample. The patient was treated with antiviral agents in combination with supportive care. Moreover, intravesical alum was administered, but no clinical benefits were achieved. Finally, intravesical alprostadil was prepared under the supervision of a pediatric clinical pharmacist. In this regard, an alprostadil solution was prepared by constitution of 250 µg alprostadil in 50 mL saline. After administrating the first dose of intravesical alprostadil, an acceptable clinical response was observed, and hematuria stopped. Of note, alprostadil induces platelet aggregation and vasoconstriction. Thus, bleeding can be controlled after the administration of intravesical alprostadil. This strategy may be associated with several side effects including bladder spasm. This study is the first report describing the special role of intravesical alprostadil in refractory cases of BK virus-associated hemorrhagic cystitis. In such refractory cases, clinicians can use intravesical alprostadil rather than invasive therapies in the treatment of BK virus-hemorrhagic cystitis.

Extracorporeal membrane oxygenation and COVID-19: The causes of failure.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic strategy for the coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). There are inconclusive data in this regard and causes of VV-ECMO failure are not yet understood well. CASE SERIES: Here, seven patients with COVID-19-induced ARDS who underwent VV-ECMO introduced and causes of VV-ECMO failure discussed. Medical records of seven COVID-19 patients treated with VV-ECMO were retrospectively evaluated to determine the clinical outcomes of VV-ECMO. Oxygenator failure occurred in four patients whom needed to oxygenator replacement. Successful VV-ECMO decannulation was done in three patients, however finally one patient survived. CONCLUSIONS: Hypercoagulability state and oxygenator failure were the most main etiologies for VV-ECMO failure in our study. All patients with COVID-19 undergoing VV-ECMO should be monitored for such problems and highly specialized healthcare team should monitor the patients during VV-ECMO.

Multiple pigmented macules as a sequel of cosmetic lip micro-pigmentation: New clinical presentation of tattoo reactions.

Cosmetic tattooing using micro-pigmentation has gained popularity in recent years. Tattoos can cause a broad range of clinical and psychosocial problems. Several medical complications may arise after tattooing. A 35-year-old female was referred with an 8-week history of grey-to-smoky hyperpigmentation of permanent makeup of lips and lip lines. Histopathological examination revealed lichenoid lymphocytic infiltrations in the dermis. Clinical and histopathological findings were compatible with the diagnosis of multiple pigmented macules as a sequel of cosmetic lip micro-pigmentation. Here, we report the first case of lichenoid-type tattoo reactions with new presentation as multiple asymptomatic pigmented macules after lip tattooing. The current report emphasises the requirement of a skin biopsy of all tattoo reactions. Considering the new component in the tattoo material, a dermatologist should be aware of the new clinical presentation of tattoo reactions that may occur.

Unusual cause of breast wound: postoperative pyoderma gangrenosum.

Postoperative pyoderma gangrenosum (PPG) is an unusual clinical entity, which shows rapidly progressive skin necrosis that can occur within surgical sites after any surgical procedure. Usually, it is diagnosed as wound infection at the time of presentation, but antibiotic therapy and wound debridement fail to arrest rapid ulcer enlargement. We report the case of PPG in a 21-year-old woman after a reduction mammoplasty surgery. In this report, we emphasise the importance of considering pyoderma gangrenosum (PG) as one of the differential diagnoses of breast ulcers after surgical procedures. Careful clinical assessment may establish an early diagnosis and prevent potential serious complications.

Unusual cause of lower extremity wounds: Cobb syndrome.

Cobb syndrome (Cutaneomeningospinal Angiomatosis) is a rare segmental neurocutaneous syndrome associated with metameric cutaneous and spinal cord arteriovenous malformations (AVMs). In this syndrome, capillary malformation or angiokeratoma-like lesions are formed in a dermatomal distribution, with an AVM in the corresponding segment of the spinal cord. The spinal cord lesions can cause neurological disorder and paraplegia, which typically develop during young adulthood. We report a 32-year-old male with the Cobb syndrome associated with lower extremity painful wounds and acute-onset paraplegia due to metameric vascular malformations.

Efficacy of intravenous immunoglobulins (IVIG) in COVID-19 patients: a systematic review and meta-analysis.

Background and purpose: Though controversial, many clinical trials have been conducted to evaluate the efficacy of intravenous immunoglobulins (IVIG) in COVID-19 cases. Therefore, a systematic review and meta-analysis have been performed to evaluate the efficacy of IVIG in the treatment of COVID-19 patients. Experimental approach: A systematic search was performed in electronic databases and preprint servers up to November 20, 2021. Since substantial heterogeneity was expected, a random-effects model was applied to pool effect size from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable with 95% confidence intervals (CIs). Findings/Results: Five randomized clinical trials and seven cohort studies were analyzed among the 12 eligible studies with a total of 2,156 patients. The pooled RR of mortality was 0.77 (CI 0.59-1.01, P-value = 0.06), and of mechanical ventilation was 1.50 (CI 0.29-7.83; P-value = 0.63) in the IVIG group compared with the standard care group. The pooled SMD of hospital length of stay was 0.84 (CI -0.43-2.11; P-value = 0.20) and of ICU length of stay was -0.07 (CI -0.92-0.78; P-value = 0.86) in the IVIG group compared with the standard care group. Conclusion and implications: This meta-analysis found that the IVIG therapy was not statistically different from the standard care group. Mortality, ICU admission, mechanical ventilation, length of hospital stay, and length of ICU stay were not significantly improved among IVIG recipients. However, statistical indifference is not equal to clinical indifference.

Hepatotoxicity Induced by Azole Antifungal Agents: A Review Study.

Context: Fungal infections are very common, and several medications are used to treat them. Azoles are prescribed widely to treat fungal infections. In addition to therapeutic effects, any drug can be accompanied by side effects in patients. One of the most important complications in this regard is liver injury. Therefore, hepatotoxicity induced by azole antifungal drugs were reviewed in this study. Evidence Acquisition: English scientific papers were evaluated to review the effects of hepatotoxicity by azole antifungal agents, and the related studies' results were summarized using a table. The systematic search was implemented on electronic databases, including PubMed, Google Scholar, and Science Direct. Original articles and review articles that were published before April 1, 2022, were included in the study. Those articles without available full text or non-English articles were excluded. Also, articles that reported pediatric data were excluded. Results: Most studies have reported the effects of hepatotoxicity by azole antifungal agents, and their mechanisms have been described. Conclusions: Clinical evaluations regarding the hepatotoxicity of antifungal agents provided in the literature were reviewed. Therefore, it is recommended to prescribe these drugs with caution in high-risk patients suffering from liver diseases, and patients should be monitored for hepatotoxicity. However, more research is needed to evaluate the hepatotoxicity of azole antifungal agents and select appropriate drugs according to cost-effectiveness and the side effects' profiles, relying on lower incidence of this liver complication.

Sputnik-V vaccine-induced panniculitis as a local reactions.

Here, a case of Sputnik-V vaccine-induced panniculitis was reported. The patient developed erythema, induration, and local tenderness at the injection site after 13 days of the injection. Ultra-sonography imaging showed inflammation in subcutaneous layers including fat tissue compatible with panniculitis. She received ibuprofen and warm compress, and all symptoms resolved.

Liquid vitamin E injection for cosmetic facial rejuvenation: A disaster report of lipogranuloma.

BACKGROUND: The use of vitamin E for Facial rejuvenation is a dangerous practice and is associated with potential local, and sometimes systemic and life-threatening complications. Clinicians should be aware of complications induced by the injection of illegal products for tissue augmentation. Also, regulatory organizations should monitor illegal beauty centers and enact restrictive laws. CASE PRESENTATION: Herein, we report a case of liquid vitamin E injection for cosmetic facial rejuvenation and development of facial persistent erythema and induration, treated with oral prednisolone, azathioprine, and minocycline. Also, we review the reported cases of vitamin E injection for cosmetic facial rejuvenation. CONCLUSION: Lipogranuloma is one of those complications of vitamin E injection for cosmetic rejuvenation. It mostly represents inflammation, edema, erythema, and tenderness. Since there was no standard treatment for this complication, the management of these patients is challenging. Patients who have undergone cosmetic interventions in illegal institutions are more likely to develop such complications including medical and psychological problems. Clinicians should be aware of these complications for the best diagnosis and treatment.

The Efficacy of an Oral Formulation of Glycyrrhiza glabra, Viola odorata, and Operculina turpethum as an Add-on Therapy for Mild-to-moderate Childhood Asthma: A Randomized Placebo-Controlled Clinical Trial.

Objective: We aimed to evaluate the efficacy of an oral combined tablet of Glycyrrhiza glabra, Viola odorata, and Operculina turpethum (Anti-Asthma®) as an add-on therapy for the relief of the severity of symptoms in mild-to-moderate childhood asthma. Methods: This randomized placebo-controlled clinical trial was performed on 60 children and adolescents with chronic mild-to-moderate childhood asthma. Patients were randomly divided into cases who received Anti-Asthma® oral combined tablets 2 tablets twice dailt for 1 month and controls, received placebo tablets identically the same to Anti-Asthma® (2 tablets, twice daily, for 1 month) as add-ons to their standard therapy according to the guideline. The severity and frequency of cough attacks and shortness of breath, respiratory test indices (based on spirometry), and the extent of disease control and treatment adherence were measured clinically by validated questionnaires at the beginning and after the study. Findings: Respiratory test indices improved and the severity of activity restriction decreased significantly in the cases compared to the controls However, the mean difference before and after the study was significantly different between the cases and controls only for the number and severity of coughs and the severity of activity restriction. In the scores of the Asthma Control Questionnaire, the cases group had a significant improvement compared to the controls. Conclusion: Anti-Asthma® oral formulation may be effective as an adjunct add-on treatment in the maintenance therapy of mild-to-moderate childhood asthma.

Efficacy and Safety of Two Different Enoxaparin Doses for Thromboprophylaxis in Non-critically Ill Patients: A Randomized Controlled Trial.

Background: Recently, a few studies based on anti-factor Xa activity levels have propounded doubtful and sub-prophylactic levels by the usual dose of enoxaparin in surgical and critically ill patients. In this study, we assessed two doses of enoxaparin in adult non-critically ill patients. Methods: Patients were randomly assigned into two groups of intervention and control. While the intervention group received enoxaparin with a daily dose of 60 mg, the control group received enoxaparin 40 mg. Anti-factor Xa activity was measured based on the peak steady-state levels. The level of 0.2 to 0.4 IU/mL was considered as a prophylactic goal. All individuals were followed for bleeding or thromboembolic events during admission. Results: The mean levels of anti-factor Xa were 0.29 ± 0.13 IU/mL in the control group (n = 31) and 0.44 ± 0.19 IU/mL in the intervention group (n = 29). More patients in the control group had an optimal level of anti-factor Xa compared to the patients in the intervention group (62.1% vs. 29%). No adverse outcomes were detected in any of the groups. Conclusions: Enoxaparin dose of 60 mg daily provided anti-factor Xa level higher than desired in most patients. In non-critically ill patients, the dose of 40 mg is the proper dose for thromboprophylaxis.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

A 5 Years Assessment of Patients with Acute Digoxin Poisoning: A Toxicoepidemiology Study in Iran.

Background: Digoxin poisoning leads to the development of cardiac and noncardiac complications. Digoxin immune fab is a safe and effective antidote, but clinical trials have not been performed in this regard, and most of the evidence is based on prospective studies. Understanding the toxicoepidemiology pattern of digoxin poisoning could provide valuable context for better managing its acute poisoning. Objectives: This study aimed to assess the toxicoepidemiology pattern of acute digoxin poisoning through a 5-year assessment in Iran. Methodology: In this observational study, the records of 97 patients who were referred with acute digoxin poisoning between 2010 and 2015 were evaluated. Demographic characteristics, past medical history, drug history, chief complaints, vital signs, paraclinical findings, digoxin immune fab administration, and clinical outcomes recorded. Results: The mean age of patients was 34.02 ± 17.87 years old. About 24.7% of patients had underlying diseases, and among them, heart failure was the most prevalent disease (29.2%) 42.3% of patients needed intensive care unit (ICU) admission. The mean duration of ICU stay was 4.00 ± 2.29 days. Digoxin immune fab was administered for 4.1% of patients, and an average of 6.2 ± 2.2 vials were used for them. All patients survived, and no mortality was reported. Conclusions: Digoxin immune fab administration did not alter the mortality rate. Hence, it can be concluded digoxin immune fab is not appropriate in acute poisoning, but it may be considered in chronic poisoning. Furthermore, acute digoxin poisoning is more common in Iran, and it responds appropriately to conventional treatment.

Patients' Satisfaction with the Community Pharmacy Services in Iran.

OBJECTIVE: This study aimed to measure patient satisfaction with community pharmacy in Isfahan, Iran, in 2019. METHODS: In this cross-sectional study (2019), we selected 104 pharmacies located in the second largest city of Iran (Isfahan) based on systematic random sampling and at least five clients at different times of a day who finished the process of obtaining medications from the pharmacies were randomly selected for a short and structured interview using the Persian version of the MacKeigan and Larson questionnaire for measuring patients' satisfaction with pharmacy services. FINDINGS: The reliability of the questionnaire was confirmed after distributing 520 among the patients (r = 0.958). No significant difference was observed between sex, marital status, housing status, and total satisfaction score based on the results. In addition, there was a significant difference between educational levels, location, job status, insurance status, real income, and total score of satisfaction (P < 0.05). Our results revealed acceptable satisfaction in some aspects, such as paying attention to pharmacists, the general condition of the pharmacy, and their technical competence. On the other hand, the patients were not satisfied enough in different aspects, for example, counseling, accessibility to their needed drugs, and expenses. CONCLUSION: Patient satisfaction needs to be improved and enhanced in the case of counseling the patients on their medications, and drug accessibility and expenses remain the primary source of dissatisfaction in the studied population, which should be noted by the Iranian Food and Drug Organization and other related authorities.

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.