The effects of colchicine on hospitalized COVID-19 patients: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate the effects of colchicine in the improvement of clinical outcomes of hospitalized COVID-19 patients. This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on adult patients (>18 years) with severe COVID-19. The included patients were randomly (1:1) assigned to the colchicine (2 mg loading dose followed by 0.5 mg twice daily for 7 days) or placebo group. Both groups received remdesivir and interferon beta-1b. The primary outcome of the study was to receive clinical response as ordinal scale of 1 or 2. Secondary outcomes were hospital complications and 28-day mortality. Between February and May 2021, 110 patients were included and 106 of them were analyzed. Baseline clinical characteristics and demographics were not significantly different. According to the ordinal scale, 30 patients in the control group (58.8%) responded to treatment within 7 days, while 35 patients (63.6%) in the colchicine group showed the same response (p = 0.61, odds ratio (OR) = 1.23, 95% CI [0.560-2.68]). On the 14th day, 87.3% of the colchicine group (n = 48) and 82.4% of the control group (n = 42) responded (p = 0.48, OR = 1.47, 95% CI [0.50.3-4.29]. In addition, 28-day mortality, intensive care unit admission, and hospital duration were not different between the groups (p = 0.99, 0.59, 0.06). Diarrhea and nausea were the major side effects dominant in the colchicine group. Colchicine showed no beneficial effects on clinical improvement and hospital complications in patients with COVID-19. Moreover, in case of prescription, the safety concerns of colchicine, specially gastrointestinal side effects, should be taken into account.

The effects of bupropion on sexual dysfunction in female patients with multiple sclerosis: A double-blind randomized clinical trial.

BACKGROUND: Sexual dysfunction (SD) is one of the most common complications of multiple sclerosis (MS). The aim of this study was to evaluate the effects of bupropion on SD among female patients with MS. METHODS: This double-blind placebo-control randomized clinical trial was conducted on MS patients with SD complaint. Diagnosis was based on the secondary SD subscale scores of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). Accordingly, individuals scoring above 27 based on this scale were diagnosed with SD. The subjects were randomly assigned to the bupropion and placebo groups. Bupropion was administered 75 mg twice daily for twelve weeks. As for the study outcomes, besides MSISQ-19, quality of life (Multiple Sclerosis Quality Of Life-54 (MSQOL-54)), fatigue (Multidimensional Fatigue Inventory (MFI)), depression and anxiety (Hospital Anxiety and Depression Scale), and bupropion tolerability were assessed at baseline as well as at weeks 6 and 12. RESULTS: From 84 patients who met the inclusion criteria, 64 patients completed the trial and were analyzed. Demographics and baseline clinical characteristics were not significantly differed between the two groups. The results showed the mean score of MSISQ-19 from baseline to the end of the study period significantly improved in the bupropion group compared with the placebo (week 6: P: 0.03; week 12: P: 0.03). Similarly, MFI scores showed significant improvement in the bupropion group compared with the placebo group (P: 0.001). Both anxiety and depression scores showed significant alterations at study interval between the two groups (Anxiety: weeks 6 and 12: P:0.04; depression: week 6: 0.01, week 12: 0.02). However, there was no significant change in the MSQOL-54 score between the two groups. CONCLUSION: The results of the study substantiated that bupropion can be an effective agent for SD improvement in female patients with MS. Further clinical trials with larger sample sizes can more accurately evaluate the observed findings.

Pyridoxine for treatment of levetiracetam-induced behavioral adverse events: A randomized double-blind placebo-controlled trial.

BACKGROUND: Levetiracetam is a broad-spectrum antiseizure medication with known behavioral side effects. The possible beneficial effect of pyridoxine on improvement of these psychiatric problems has been suggested in few previous studies. This clinical trial aimed to investigate the effect of pyridoxine on behavioral side effects of levetiracetam in adult patients with epilepsy. METHODS: This study was a randomized double-blind placebo-controlled clinical trial on 53 adult patients with epilepsy with behavioral side effects after treatment by levetiracetam. Patients who met the study criteria were randomized to receive 40 mg/day pyridoxine or placebo. Their psychiatric state was surveyed by SCL-90-R questionnaire before and three weeks after initiation of treatment. RESULTS: There were no statistically significant differences in the behavioral adverse effects between the pyridoxine-treated group and the placebo group. CONCLUSION: Although this study showed no statistically significant beneficial effects of pyridoxine on the behavioral adverse effects of levetiracetam, placebo-controlled trials with a larger size and higher doses are needed to determine whether it is effective or not.

The Effects of COVID-19 on Patients with Acute Ischemic and Hemorrhagic Stroke.

OBJECTIVE: The objective of this study was to evaluate how COVID-19 affects patients with acute ischemic or hemorrhagic stroke outcome. MATERIALS AND METHODS: This retrospective study was performed on adult patients (> 18 years old) with stroke (ischemic or hemorrhagic) who were admitted to hospital with or without COVID-19. The primary outcome was stroke-related disability, which was measured by mRS at baseline and discharge. Hospital duration, intensive care unit (ICU) admission, and mortality were considered the secondary outcomes. RESULTS: From February 2019 until August 2020, we recruited and analyzed 151 patients, 42 of whom had COVID-19 based on RT-PCR tests or lung CT scan findings. COVID-19 positive patients had higher baseline and final mRS scores than the control group (4.46 ± 0.67 vs 4.79 ± 0.61, P: 0.001, 3.83 ± 1.22 vs 4.46 ± 0.67, P: 0.001). Moreover, stroke patients with COVID-19 experienced a more severe disease and required a higher rate of ICU admission (17 vs 0, P:0.001) and longer hospitalization compared to those without COVID-19 (8.50 ± 7.86 vs 7.5 ± 11.20, P: 0.021). Also, mortality was higher in the COVID-19 group (19 vs 13, P:0.001). There was not any significant differences between the two groups in terms of the involvement of cerebral arteries and type of stroke. Male sex, COVID-19, and ICU admission were the main independent risk factors for death. CONCLUSION: The results of the study showed stroke patients (ischemic or hemorrhagic) with COVID-19 can have more disabilities and incur more hospital complications and mortality than non-COVID-19 patients.

The effectiveness of amantadine and dalfampridine in improving fatigue in patients with multiple sclerosis: A randomized, double-blind, clinical trial.

Background: Fatigue is a common complication associated with multiple sclerosis (MS). The aim of this study was to evaluate the impact of dalfampridine and amantadine on fatigue in patients with MS. Methods: This was a randomized, double-blind, clinical trial on patients with MS. The recruited patients were adults (≥ 18 years old) diagnosed with MS; their Expanded Disability Status Scale (EDSS) was between 0.0 and 5.5, and their fatigue was confirmed by the Modified Fatigue Impact Scale (MFIS). They were randomly assigned to the amantadine (100 mg twice daily) and dalfampridine (10 mg twice daily) for eight weeks. The primary outcome was the improvement of fatigue score, and the secondary outcome was assessment of quality of life by the Short-Form Health Survey (SF-36) and any reported side effects. Results: A total of 69 patients were recruited, and 54 of them were analyzed. The mean MFIS significantly improved in both groups after one and two months compared to baseline: amantadine: first month: 40.63 ± 14.35 (P = 0.040), second month: 36.56 ± 17.12 (P = 0.010); dalfampridine: first month: 38.29 ± 15.23 (P = 0.001), second month: 34.26 ± 18.30 (P = 0.001). However, the amount of changes from baseline was not significantly different (amantadine, P = 0.090; dalfampridine, P = 0.130). The amount of changes in quality of life showed no significant improvement (P = 0.210). Conclusion: The results showed that dalfampridine was not different with amantadine in improving fatigue in patients with MS; besides, it showed an acceptable safety profile. Therefore, it can be considered as a possible beneficial therapeutic agent in MS fatigue.

Efficacy and Safety of 0.25% Timolol Gel in Healing Split-Thickness Skin Graft Site.

As a common intervention among burn patients, skin graft has some risks such as infections and delay of wound healing. The aim of this study was to assess the efficacy and safety of topical 0.25% Timolol Gel (TG) in promoting wound healing in split-thickness skin graft donor sites. We conducted a double-blind, randomized clinical trial to assess re-epithelialization time, the level of pain based on the Visual Analog Scale (VAS), and the wound infection incidence. The scar status was also evaluated by the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Totally, 64 patients were randomly assigned to the study groups. The two groups showed a significant difference in healing time (14.5 ± 3.2 vs. 11.5 ± 2.3 days, P < 0.001). No infection occurred in either group, and 3 cases of transplant rejection were observed in the placebo group. The VAS was significantly different on days 1, 2, 3, 4, and 7 (P < 0.05). In the third month, the results showed a significant difference in terms of VSS (P = 0.005). Topical TG, due to its favorable effects on wound healing and pain reduction, can be administered as a therapeutic agent in patients with a skin graft.

Reversible blindness after erroneous prescription of closantel: A case report.

A 20-year-old girl was referred with vision loss upon closantel use. Plasma exchange and high-dose corticosteroid pulse therapy were administered. A 2.5-year follow-up showed improved vision and increased layer thickness of the peripheral nerve fiber. Early treatment with plasma exchange and high-dose corticosteroid therapy can be beneficial to reverse closantel toxicity.

Pentoxifylline effects on hospitalized patients with COVID19: A randomized, double-blind clinical trial.

Pentoxifylline (PTX) has broad-spectrum properties such as anti-inflammatory, anticoagulant, and antiviral effects. The aim of this study was to evaluate the efficacy and safety of PTX in hospitalized patients with COVID-19. This double-blind, placebo-controlled randomized clinical trial was conducted on hospitalized patients with COVID-19. The recruited patients were randomly (1:1) assigned to the PTX group and the placebo group. The intervention group received PTX capsules at a dose of 400 mg three times a day for 10 days along with the national regimen, including interferon plus lopinavir/ritonavir and hydroxychloroquine. The primary outcome was the improvement of clinical scores. The secondary outcomes, on the other hand, were improvement in inflammatory and oxidative stress factors and hospital complications. From a total of 102 patients who met the inclusion criteria, 72 individuals completed the study and were analyzed. No significant differences were shown in demographics and baseline clinical characteristics. Clinical scores was not significant between the two groups (P = 0.31 and 0.07 for day 5 and 11, respectively). Although the mean serum levels of interleukin-6 (IL-6) and glutathione changed significantly after 5 days in the PTX group (P = 0.03 and p = 0.04), ICU admission, intubation, and hospital stay did not differ between the two groups. The results of our study did not show any superiority of PTX over placebo in improving the clinical outcomes of patients with COVID-19. Although PTX had a beneficial effect on IL-6 and showed an acceptable safety profile, it did not offer any clinical benefit for COVID-19 complications.

A Clinical Monitoring Program of COVID-19 Outpatients: A Prospective Cohort Study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has been associated with a high rate of mortality and morbidity. While a high portion of COVID-19 patients have mild symptoms, a limited number of clinical trials have evaluated the clinical course of this large group of patients. This study was designed to investigate the demographics and clinical characteristics and comorbidity of nonhospitalized COVID-19 patients. METHODS: This prospective, observational cohort study was performed on nonhospitalized adult patients (≥18 years) with COVID-19. Pharmacotherapy service was responsible for patients' assessment for up to 1 month. Demographic characteristics, the onset of symptoms, severity, duration, laboratory data, and hospitalization rate were evaluated by a pharmacist-based monitoring program. RESULTS: From 323 patients who had been referred to the emergency department, 105 individuals were recruited between April 26 and August 2, 2020. Most of the patients were female (66.7%) with a mean age of 39.39 years (SD: ± 15.82). The mean time of the symptom onset was 5.6 days (SD: ±1.79). The majority of patients suffered from fatigue (78.1%), sore throat (67.6%), cough (60%), and myalgia (55.2%). C-reactive protein, white blood cell, lymphocyte, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and hemoglobin levels were recovered significantly during the first two weeks (P < 0.001). Hydroxychloroquine, naproxen, diphenhydramine, azithromycin, and vitamin D3 were the most common medications administered (98%, 96%, 94%, 68%, and 57%, respectively). Forty patients were not symptom-free after the one-month follow-up, and 8 patients (7.6%) were required to revisit without the need for hospitalization. Anosmia (18.1%) and fatigue (17.1%) were the most common persisted symptoms. There were no significant differences between symptom-free and symptomatic patients. CONCLUSION: Mild COVID-19 patients had a wide variety of symptoms and could be symptomatic even one month after the onset of symptoms. The pharmacist-based monitoring system can contribute beneficially to patients through the evaluation of symptoms, reduction of unnecessary visits, and provision of updated information to patients concerning the status of their illness.

The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.

Adverse effects of brimonidine eye drop in children: A case series.

WHAT IS KNOWN AND OBJECTIVE: Brimonidine is increasingly used in the treatment of intraocular hypertension. CASE SUMMARY: We report on five paediatric patients suffering from brimonidine eye drop intoxication. The most frequent signs of the intoxication were a lowered level of consciousness and hypotonia. Other complications were apnea, bradycardia, hypotension and seizure. One of the patients needed cardiopulmonary resuscitation. Apnea in one of the cases was resistant to naloxone. Pupils were unremarkable in two cases. WHAT IS NEW AND CONCLUSION: Brimonidine is potentially lethal for young infants. The absence of miosis and absence of response to naloxone is not a reason to rule out brimonidine poisoning.

Evaluation of Urinary Tract Infection following Corticosteroid Therapy in Patients with Multiple Sclerosis Exacerbation.

The first treatment for multiple sclerosis exacerbation is usually short-term intravenous methylprednisolone (IVMP), with or without a regimen of oral prednisone taper (OPT). This study aims to evaluate the effects of IVMP and OPT in comparison with IVMP alone in raising the risk of urinary tract infection (UTI) and posttreatment improvement of urinary tract symptoms in patients with relapsing-remitting multiple sclerosis. This double-blind randomized clinical trial was conducted on 56 people with multiple sclerosis relapse who had undergone methylprednisolone for 5 days. Patients were randomly split into two groups: oral prednisolone and placebo (tapering for 20 days). Demographic data, duration of multiple sclerosis, urinary tract symptoms, the Expanded Disability Status Scale (EDSS) score, and urine data were analyzed. The incidence of UTI in the intervention and control groups did not differ significantly (p=560). However, the improvement of urinary tract symptoms in the intervention group was significantly more favorable than in the control group (p ≤ 0.001). Furthermore, administering OPT after IVMP did not increase the risk of UTI occurrence in patients with multiple sclerosis exacerbation. The urine analysis results did not show any differences at baseline and after the corticosteroid tapering regimen. Due to the risk of infection by corticosteroids, it is no longer necessary to do further urinary screening in this group of patients.

Efficacy and safety of oral prednisolone tapering following intravenous methyl prednisolone in patients with multiple sclerosis relapses: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Relapse is one of the main features of multiple sclerosis (MS). Corticosteroids are the first line of management during MS relapse. Since tapering or non-tapering prednisolone after corticosteroid pulse has been a controversial issue, this clinical trial is designed to evaluate the efficacy and safety of the tapering regimen. METHODS: Having been treated by intravenous methylprednisolone (IVMP) pulse, sixty-six patients with MS-relapse were randomly assigned to receive oral prednisolone tapering (OPT) or placebo. The regimen was administered in line with the study protocol and the dose was tapered over 20 days. Demographics and symptoms, impact on activities of daily living (ADL), and management procedures were recorded according to Assessing Relapse in Multiple Sclerosis (ARMS) Questionnaire. The incidence of adverse events was assessed using the same questionnaire. Patients' disability improvement was assessed using the Extended Disability Scale (EDSS) during relapse, and over the first, third, sixth months following treatment. RESULTS: As shown by the results of the questionnaire, 75% reported that their ADL was not or minimally affected by OPT and there was no significant difference in terms of ADL after treatment between the two groups (p=0.3). The effect of treatment on return to the previous state of health (RSH) showed that there were no differences between the two groups of the study (p=0.5). The improvement of disability in the two groups of oral prednisolone and placebo did not indicate a difference in terms of EDSS in the first and third and six months (p = 0.5, p = 0.9, p=0.3, respectively). Also, the occurrence of some side effects such as weight gain (p = 0.000) and increased appetite (p = 0.004) was higher in the OPT group. CONCLUSION: The findings of this study revealed that the efficacy of an OPT after a corticosteroid pulse is non-superior to IVMP plus only in case the safety and tolerability profile are comparable.

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.

Once Versus Thrice Daily Colistin in Critically Ill Ptients with Multi-Drug Resistant Infections.

The aim of this study was to evaluate the procalcitonin (PCT) changes in two different high-dose colistin regimens in the treatment of multi-drug resistant MDR gram negative infections in ICU patients. This is a prospective study of adult ICU patients with bacteremia and ventilator associated pneumonia (VAP) caused by MDR gram negative pathogens. Patients were assigned to two colistin administration groups. Group A received 9 and group B received 3 million international units every 24 and 8 h respectively. Baseline characteristics and measurements of PCT concentrations at the start, the 3rd and the 5th day of the antibiotic therapy and their trends between the two groups were recorded and compared. of 40 patients enrolled, 34 completed the study protocol, of whom 30 (88.2%) had (VAP) and 4 (11.8%) had bacteremia. There were no statistically significant differences in the baseline characteristics between the two groups. The mean PCT levels in two study groups were; 2.34, 1.24, and 0.95 in group A and 5.89, 1.24 and 0.8 in group B at the baseline, 3rd and 5th day of colistin administration respectively (P=0.47). The ICU length of stay (LOS) in days and ICU mortality were; 31.31, 35.3% and 32.06, 22.2% in groups A and B (P=0.39, 0.87), respectively. CONCLUSION: We did not find any statistically significant differences in the serum PCT levels, ICU LOS or ICU mortality, between the two groups, who received maximum recommended dose of CMS with 2 different intervals of every 8 or 24 h.

Errors Related to Medication Reconciliation: A Prospective Study in Patients Admitted to the Post CCU.

Medication errors are one of the important factors that increase fatal injuries to the patients and burden significant economic costs to the health care. An appropriate medical history could reduce errors related to omission of the previous drugs at the time of hospitalization. The aim of this study, as first one in Iran, was evaluating the discrepancies between medication histories obtained by pharmacists and physicians/nurses and first order of physician. From September 2012 until March 2013, patients admitted to the post CCU of a 550 bed university hospital, were recruited in the study. As a part of medication reconciliation on admission, the physicians/nurses obtained medication history from all admitted patients. For patients included in the study, medication history was obtained by both physician/nurse and a pharmacy student (after training by a faculty clinical pharmacist) during the first 24 h of admission. 250 patients met inclusion criteria. The mean age of patients was 61.19 ± 14.41 years. Comparing pharmacy student drug history with medication lists obtained by nurses/physicians revealed 3036 discrepancies. On average, 12.14 discrepancies, ranged from 0 to 68, were identified per patient. Only in 20 patients (8%) there was 100 % agreement among medication lists obtained by pharmacist and physician/nurse. Comparing the medications by list of drugs ordered by physician at first visit showed 12.1 discrepancies on average ranging 0 to 72. According to the results, omission errors in our setting are higher than other countries. Pharmacy-based medication reconciliation could be recommended to decrease this type of error.