Evaluating the factors affecting clinical outcomes in critically ill COVID-19 unvaccinated patients admitted to the intensive care unit in a lower-middle-income country.

Background: COVID-19, the most destructive pandemic of this century, caused the highest mortality rate among ICU patients. The evaluation of these patients is insufficient in lower-middle-income countries with limited resources during pandemics. As a result, our primary goal was to examine the characteristics of patients at baseline as well as their survival outcomes, and propose mortality predictors for identifying and managing the most vulnerable patients more effectively and quickly. Methods: A prospective analysis of COVID-19 ICU-admitted patients was conducted in our healthcare centre in Iran, from 1 April until 20 May 2020. Ninety-three patients were included in the study, and all were unvaccinated. A multi-variate logistic regression was conducted to evaluate mortality-associated factors. Results: There were 53 non-survivors among our ICU-admitted patients. The mean duration from symptoms' onset to hospitalization was 6.92 ± 4.27 days, and from hospitalization to ICU admission was 2.52 ± 3.61 days. The average hospital stay for patients was 13.23 ± 10.43 days, with 8.84 ± 7.53 days in the ICU. Non-survivors were significantly older, had significantly lower haemoglobin levels and higher creatine phosphokinase levels compared to survivors. They had marginally lower SpO2 levels at admission, higher vasopressor administrations, and were intubated more significantly during their ICU stay. The use of immunosuppressive drugs was also significantly higher in non-survivors. Logistic regression revealed that a one-point increase in APACHE II score at ICU admission increased mortality by 6%, and the presence of underlying diseases increased mortality by 4.27 times. Conclusion: The authors presented clinical mortality prediction factors for critically ill patients infected with COVID-19. Additional studies are necessary to identify more generalized mortality indicators for these patients in lower-middle-income countries.

L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management.

In this review, we discussed the biological targets of carnitine, its effects on immune function, and how L-carnitine supplementation may help critically ill patients. L-carnitine is a potent antioxidant. L-carnitine depletion has been observed in prolonged intensive care unit (ICU) stays, while L-carnitine supplementation has beneficial effects in health promotion and regulation of immunity. It is essential for the uptake of fatty acids into mitochondria. By inhibiting the ubiquitin-proteasome system, down-regulating the apelin receptor in cardiac tissue, and reducing ß-oxidation of fatty acid, carnitine may decrease vasopressor requirement in septic shock and improve clinical outcomes of this group of patients. We also reviewed animal and clinical studies that have been recruited for evaluating the beneficial effects of L-carnitine in the management of sepsis/ septic shock. Additional clinical data are required to evaluate the optimal daily dose and duration of L-carnitine supplementation.

Study of the frequency and clinical features of maturity-onset diabetes in the young in the pediatric and adolescent diabetes population in Iran.

OBJECTIVES: Maturity-onset diabetes of the young (MODY), an autosomal dominant disease, is frequently misdiagnosed as type 1 or 2 diabetes. Molecular diagnosis is essential to distinguish them. This study was done to investigate the prevalence of MODY subtypes and patients' clinical characteristics. METHODS: A total of 43 out of 230 individuals with diabetes were selected based on the age of diagnosis >6 months, family history of diabetes, absence of marked obesity, and measurable C-peptide. Next-generation and direct SANGER sequencing was performed to screen MODY-related mutations. The variants were interpreted using the Genome Aggregation Database (genomAD), Clinical Variation (ClinVar), and pathogenicity prediction tools. RESULTS: There were 23 males (53.5%), and the mean age at diabetes diagnosis was 6.7 ± 3.6 years. Sixteen heterozygote single nucleotide variations (SNVs) from 14 patients (14/230, 6%) were detected, frequently GCK (37.5%) and BLK (18.7%). Two novel variants were identified in HNF4A and ABCC8. Half of the detected variants were categorized as likely pathogenic. Most prediction tools predicted Ser28Cys in HNF4A as benign and Tyr123Phe in ABCC8 as a pathogenic SNV. Six cases (42.8%) with positive MODY SNVs had islet autoantibodies. At diagnosis, age, HbA1c, and C-peptide level were similar between SNV-positive and negative patients. CONCLUSIONS: This is the first study investigating 14 variants of MODY in Iran. The results recommend genetic screening for MODY in individuals with unusual type 1 or 2 diabetes even without family history. Treatment modifies depending on the type of patients' MODY and is associated with the quality of life.

Clinical Effectiveness of a High Dose Versus the Standard Dose of Meropenem in Ventilator-associated Pneumonia Caused by Multidrugresistant Bacteria: A Randomized, Single-blind Clinical Trial.

BACKGROUND: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). ; Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard-dose group, 13 patients) as a 3h infusion. The primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. Sputum culture was taken before the intervention. ; Results: Clinical success rate was not significantly different between the high and standard-dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in the reduction of clinical pulmonary infection score (CPIS) compared to a high dose to the standard group (P=0.038). SOFA score declined significantly in the high dose group throughout the study (P=0.006). A shorter duration of VAP treatment was recorded in the high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. ; Conclusion: Treatment with the high dose of meropenem seems to be safe. However, it did not provide a significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reduction in SOFA and CPIS. ; The trial protocol was registered with IRCT.ir (registration number IRCT2010010700 3014N19 in April 2018).

Update on Statin Treatment in Patients with Neuropsychiatric Disorders.

Statins are widely accepted as first-choice agents for the prevention of lipid-related cardiovascular diseases. These drugs have both anti-inflammatory and anti-oxidant properties, which may also make them effective as potential treatment marked by perturbations in these pathways, such as some neuropsychiatric disorders. In this narrative review, we have investigated the effects of statin therapy in individuals suffering from major depressive disorder (MDD), schizophrenia, anxiety, obsessive-compulsive disorder (OCD), bipolar disorder (BD), delirium, and autism spectrum disorders using a broad online search of electronic databases. We also explored the adverse effects of these drugs to obtain insights into the benefits and risks associated with their use in the treatment of these disorders. Lipophilic statins (including simvastatin) because of better brain penetrance may have greater protective effects against MDD and schizophrenia. The significant positive effects of statins in the treatment of anxiety disorders without any serious adverse side effects were shown in numerous studies. In OCD, BD, and delirium, limitations, and contradictions in the available data make it difficult to draw conclusions on any positive effect of statins. The positive effects of simvastatin in autism disorders have been evaluated in only a small number of clinical trials. Although some studies showed positive effect of statins in some neuropsychiatric disorders, further prospective studies are needed to confirm this and define the most effective doses and treatment durations.

Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran.

Objectives Type 1 diabetes is an autoimmune disease. Its most important immunologic markers are pancreatic beta-cell autoantibodies. This study aimed to determine diabetes mellitus antibodies frequency among children and adolescents with type 1 diabetes. Methods This descriptive study evaluated the frequency of four diabetes autoantibodies (glutamic acid decarboxylase 65 autoantibodies [GADA], islet cell autoantibodies [ICA], insulin autoantibodies [IAA], tyrosine phosphatase-like insulinoma antigen-2 antibodies [IA-2A]) and their serum level in children and adolescents diagnosed with type 1 diabetes mellitus at the diabetes department of Bou-Ali-Sina Hospital and Baghban Clinic, Sari, Iran, from March 2012 to March 2018. The relationship between the level of different antibodies and age, gender, and diabetes duration were determined. A two-sided p value less than 0.05 indicated statistical significance. Results One hundred forty-two eligible patient records were screened. The average age at diabetes diagnosis was 4.2 ± 4.4 years. The median duration of diabetes was 34.0 (12.7-69.7) months. 53.5% of patients were female, and 81.7% of them had at least one positive autoantibody, and ICA in 66.2%, GADA in 56.3%, IA-2A in 40.1%, and IAA in 21.8% were positive. The type of the autoantibodies and their serum level was similar between females and males but there was a higher rate of positive autoantibodies in females. The level of IA-2A and ICA were in positive and weak correlation with age at diagnosis. Conclusions More than 80% of pediatric and adolescent patients with type 1 diabetes were autoantibody-positive. ICA and GADA were the most frequently detected autoantibodies. The presence of antibodies was significantly higher in females.

Evaluation of Cholestyramine 15% Ointment in Relieving Pruritus and Burning After Ileostomy: A Rrandomized, Double-Blind Placebo-Controlled Clinical Trial.

Purpose/Aims: Skin irritation is a common ileostomy problem that causes burning and pruritus among patients due to the leakage of intestinal discharge around the stoma. This clinical trial was performed to evaluate the efficacy of topical cholestyramine (15%) on the reduction of the levels of burning and pruritus after an ileostomy. Material and methods: The patients were randomly divided into two groups of treatment and control (n = 15). The intervention group was subjected to one fingertip of cholestyramine, whereas the other group received the placebo ointment (approximately 0.5 g) on the skin immediately after the surgery and twice a day for 2 months. The primary outcome measure was the severity of burning and pruritus measured by a visual analog scale at different times after an ileostomy. Results: Out of 34 patients, four cases were excluded due to the inappropriate completion of the questionnaire (n = 2) and unwillingness to attend the follow-up visits (n = 2). Therefore, 30 patients were included in the study. The levels of burning among patients in the cholestyramine were lower in weeks 3, 4, and 8 compared to the placebo group. Moreover, lower levels of pruritus were observed among patients in the treatment group in weeks 4 and 8 after an ileostomy. No side effects were reported among the patients. Conclusions: Topical cholestyramine was found to be effective in the management of burning and pruritus resulting from an ileostomy among the population under study.

Effect of Topical Baclofen 5% on Post-Hemorrhoidectomy Pain: Randomized Double Blind Placebo-Controlled Clinical Trial.

BACKGROUND: Baclofen is an agonist for a subtype of gamma-amino butyric acid (GABA-B) receptors and traditionally been used for the systemic treatment of spasticity. Topical application of baclofen has been shown to reduce pain in patients with localized neuropathic pain. OBJECTIVES: In this study, we investigate the efficacy of baclofen cream (5%) in reducing postoperative pain and analgesic requirement after open hemorrhoidectomy. DESIGN: The patients were randomly assigned to either baclofen (5%) cream or placebo immediately after surgery and then every 12 h for 14 days. PATIENTS: A total of 66 patients with third- and fourth-degree hemorrhoids undergoing open hemorrhoidectomy were randomly assigned to this trial. SETTING: This study was conducted at a single educational hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were intensity of pain, measured with a visual analog scale, and the analgesic requirement, measured by the amount of the acetaminophen consumption. RESULTS: No significant difference was found in baseline characteristics between the two groups. Postoperative pain score of the baclofen group was significantly lower on week 1 (P = 0.01) and week 2 (P = 0.02) than the placebo group. Similarly, patients in the baclofen group consumed significantly less analgesic medication on week 1 (P = 0.025) and week 2 (P = 0.024) than the control group. CONCLUSION: Topical application of baclofen effectively relieves pain after hemorrhoidectomy with minimal side effects.