Effects of atypical antipsychotics on serum asprosin level and other metabolic parameters in patients with schizophrenia.

BACKGROUND: In this cross-sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics (olanzapine, risperidone, or aripiprazole) and healthy subjects. METHODS: The study population included 62 adult outpatients with schizophrenia and 22 healthy controls, matched for age and gender. Patients were in remission and had been on stable monotherapy with one of these atypical antipsychotics for over 6 months. Body Mass Index (BMI) and fasting serum levels of asprosin, glucose, HA1c, insulin, and lipid profile were compared across the investigated groups. Additionally, the number of participants meeting the insulin resistance criterion, defined as homeostasis model assessment for insulin resistance (HOMA-IR) >2.5, as well as the number of participants with elevated BMI levels (men >27 kg/m2, women >25 kg/m2) were compared among the groups. RESULTS: We observed statistically significant differences in BMI and fasting serum levels of glucose, HA1c, insulin, triglyceride (TG), high-density lipoprotein cholesterol, and asprosin among patients receiving olanzapine or risperidone, as compared to those receiving aripiprazole and healthy subjects. Patients on aripiprazole exhibited values comparable to healthy subjects, whereas those on risperidone or olanzapine showed significantly higher values, with the highest observed in the olanzapine group. Additionally, the prevalence of participants meeting the insulin resistance criterion and those with elevated BMI was also greater in individuals receiving olanzapine or risperidone compared to those on aripiprazole and healthy subjects. Serum asprosin levels showed a significant positive correlation with BMI and several metabolic parameters, including HbA1c, fasting insulin, HOMA-IR, and TG. No significant differences were observed among the investigated groups in terms of serum levels of total cholesterol and low-density lipoprotein cholesterol. CONCLUSIONS: Our cross-sectional study highlights the association between elevated asprosin levels, weight gain, and metabolic disorders in patients treated with olanzapine and risperidone. Given the bidirectional nature of the relationship between serum asprosin levels and these metabolic disturbances, further research is warranted to elucidate potential causative pathways.

Immunogenicity of Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) and Short-Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study.

BackgroundImmunocompromised patients have lower seroconversion rate in response to COVID-19 vaccination. The aim of this study is to evaluate the humoral immune response with short-term clinical outcomes in solid organ transplant recipients vaccinated with SARS-CoV-2 vaccine (BBIBP-CorV; Sinopharm).MethodsThis prospective cohort was conducted from March to December 2021 in Abu Ali Sina hospital, Iran. All transplant recipients, older than 18 years were recruited. The patients received two doses of Sinopharm vaccine 4 weeks apart. Immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 after the first and second dose of vaccine. The patients were followed up for 6 months after vaccination.ResultsOut of 921 transplant patients, 115 (12.5%) and 239 (26%) had acceptable anti S-RBD immunoglobulin G (IgG) levels after the first and second dose, respectively. Eighty patients (8.68%) got infected with COVID-19 which led to 45 (4.9%) of patients being hospitalized. None of the patients died during follow-up period. Twenty-four (10.9%) liver transplant recipients developed liver enzyme elevation, and increased serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two patients experienced biopsy-proven rejection without any graft loss.ConclusionOur study revealed that humoral response rate of solid organ transplant recipients to Sinopharm vaccine was low.

Coenzyme Q10 as a potential add-on treatment for patients suffering from painful diabetic neuropathy: results of a placebo-controlled randomized trial.

BACKGROUND: We hypothesized that the addition of coenzyme Q10 (CoQ10) to pregabalin might be helpful in improving symptoms in patients suffering from painful diabetic neuropathy (PDN). METHODS: One hundred twelve patients with PDN were randomly allocated to receive CoQ10 + pregabalin (57 patients) or placebo + pregabalin (55 patients). Besides pregabalin (150 mg/day), the patients, upon their group assignment, received CoQ10 at a dosage of 100 mg every 8 h or matched placebo for 8 consecutive weeks. The primary efficacy measure was the changes in the pain intensity from baseline to endpoint measured on an 11-point NRS (numeric rating scale). Secondary efficacy measures included the changes in the pain-associated sleep interference score (SIS) as well as the patients' global improvement with treatment measured on the Clinicians' and Patients' Global Impression of Change (CGIC/PGIC). RESULTS: On the intent­to­treat population (ITT) analysis, the CoQ10 + pregabalin regimen resulted in significantly greater pain relief than the placebo + pregabalin regimen. By the end of week 2, the decrease in the mean pain NRS score was similar in both groups, but at the end of weeks four and eight, the decrease in the mean pain NRS score was significantly greater in patients taking CoQ10 + pregabalin than in those taking placebo + pregabalin (p value = 0.01 and < 0.001, respectively). Likewise, at the end of week 8, the decrease in the pain-associated SIS was significantly greater in the patients supplemented with CoQ10 compared to placebo. Furthermore, the proportion of the responder patients (those having ≥ 50% decline in the mean pain NRS score) as well as the proportion of patients rated ''very much'' or ''much improved'' on the CGIC/PGIC scales were also significantly higher in the CoQ10 + pregabalin-treated patients than placebo + pregabalin-treated patients. CONCLUSIONS: Our data support the idea that diabetic patients suffering from PDN may benefit from using antioxidant and anti-inflammatory supplements like CoQ10. However, further studies are required before supplementation with CoQ10 can be recommended for treating PDN. TRIAL REGISTRATION: The trial was registered at Iranian Registry of Clinical Trials (identifier code: IRCT20120215009014N385). Registration date: 2021-02-21.

Influence of Simvastatin as Augmentative Therapy in the Treatment of Generalized Anxiety Disorder: A Pilot Randomized, Placebo-Controlled Study.

BACKGROUND: Preliminary evidence is promising regarding the anxiolytic effects of statins in animal models of anxiety. Hence, this study aimed to evaluate the efficacy of simvastatin augmentation versus placebo in the treatment of patients with generalized anxiety disorder (GAD) with residual symptoms despite treatment with selective serotonin reuptake inhibitors (SSRIs). METHODS: A double-blind, 8-week controlled trial was conducted from August 2018 to December 2019 in an outpatient psychiatry clinic in Hamadan, Iran. A total of 138 patients with a diagnosis of GAD were assessed for eligibility. Of them, 84 patients who met the study criteria were randomly assigned either to the adjuvant simvastatin (20 mg/day) or to the placebo group. Standard medication consisting of SSRIs was consistent 2 months prior to and during the study. The severity of anxiety symptoms for each patient was assessed based on the Hamilton Anxiety Rating Scale (HAM-A) score at baseline, week 4, and week 8 after treatment. Additionally, blood lipid values were assessed at baseline and on completion of the study. RESULTS: Thirty-three out of 42 patients in the intervention group and 35 out of 42 patients in the control group completed the 8 weeks of the study period. Compared to the placebo group, in the simvastatin group cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and high-density lipoprotein significantly increased over time. General linear model analysis demonstrated that although over time a higher decrease in mean HAM-A scores was observed in the intervention group compared to the control group, this difference was not statistically significant (p = 0.11). In addition, at the end of the study, the number of responders and remitters was comparable in the two groups. CONCLUSIONS: The results from this clinical study did not support the potential efficacy of adjunctive simvastatin in the treatment of patients with GAD. Thus, large-scale and long-term clinical trials are required to more accurately assess the potential efficacy of statins in the treatment of patients with anxiety disorders.

Comparison of the effects of empagliflozin and sitagliptin, as add-on to metformin, on serum levels of asprosin and metabolic parameters in patients with type 2 diabetes mellitus.

The effect of sitagliptin and empagliflozin on serum levels of asprosin and metabolic parameters in patients with type 2 diabetes mellitus (T2DM) was assessed in a non-randomized, prospective observational study. Seventy-nine T2DM patients, without adequate glycemic control with metformin monotherapy, were included in the study. In addition to the ongoing metformin treatment, patients received sitagliptin 100 mg and empagliflozin 10 mg once daily for 12 weeks. Anthropometric parameters, lipid and glycemic profile, insulin resistance (homeostasis model assessment of insulin resistance index [HOMA-IR]), and asprosin serum levels were assessed at baseline and after 12 weeks of therapy. Both empagliflozin and sitagliptin treatments led to similar, significant improvement in fasting blood glucose (FBG) and hemoglobin A1C (HbA1C). Compared to baseline, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were improved with both treatments, but empagliflozin led to the more improvement. No significant change of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were observed in either group. Insulin resistance was significantly attenuated in both groups, but to a greater degree with empagliflozin treatment. The reduction in serum asprosin levels from baseline was significantly higher in patients taking empagliflozin compared to those receiving sitagliptin. Additionally, individuals on empagliflozin exhibited a more decrease in body mass index (BMI) and body weight compared to those on sitagliptin. According to our findings, the addition of empagliflozin to metformin appeared to offer greater benefits compared to the addition of sitagliptin in terms of decreasing asprosin levels and improving certain metabolic parameters in T2DM patients.

The clinical and paraclinical effectiveness of four-hour infusion vs. half-hour infusion of high-dose ampicillin-sulbactam in treatment of critically ill patients with sepsis or septic shock: An assessor-blinded randomized clinical trial.

PURPOSE: This study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion. MATERIAL AND METHODS: This randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min. RESULTS: Totally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group. CONCLUSION: These data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice.

N-Acetyl Cysteine as an Add-on Therapy is Useful in Treating Acute Lumbar Radiculopathy Caused by Disc Herniation: Results of a Randomized, Controlled Clinical Trial.

BACKGROUND: Available experimental and clinical evidence indicates that N-Acetyl cysteine (NAC) may have an analgesic role in specific pain conditions, particularly neuropathic pain. Thus, we hypothesized that NAC supplementation might be also helpful in decreasing pain and improving pain-related disability in patients with acute radiculopathy. We designed this study to investigate the potential use of NAC-adjunctive treatment to Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) in patients with acute radiculopathy secondary to lumbar intervertebral disc herniation. METHODS: Sixty-two patients diagnosed with acute lumbar radiculopathy associated with disc herniation were randomly allocated to the NAC or the placebo groups. Besides naproxen at a dose of 500 mg twice a day, participants based on their allocation group started with NAC or matched placebo at a dose of 600 mg twice a day for eight weeks. The pain severity, measured by the Visual Analog Scale (VAS), and pain-related disability measured by the Oswestry Disability Index (ODI) were measured at baseline and weeks 2, 4, and 8 of treatment. Global improvement of symptoms rated by Patient and Clinical Global Impressions of Change (PGIC and CGIC) was also recorded at the end of week 8. All analyses were conducted on an Intentionto- Treat (ITT) analysis data set. RESULTS: A comparison of the VAS and ODI scores at weeks 2 and 4 of the treatment between the two groups did not show a significant difference. In contrast, from week 4 to week 8, we noticed a significantly greater reduction in the mean VAS and ODI scores in the NAC group compared to the placebo group (p-value <0.001 for both variables). In parallel with these results, also, more NAC-treated than placebo-treated patients achieved treatment success defined as ''very much'' or ''much improved'' on CGIC and PGIC scales, and these differences reached a significant level (p-value = .011 and p-value = .043). CONCLUSIONS: This study suggested that NAC might be a relevant candidate for adjunct therapy in managing acute lumbar radiculopathy. Additional clinical trials are needed to validate these findings.

Pharmacological agents for the prevention of colistin-induced nephrotoxicity.

BACKGROUND: Colistin is a polymyxin antibiotic which has been used for treatment of Gram-negative infections, but it was withdrawn due to its nephrotoxicity. However, colistin has gained its popularity in recent years due to the reemergence of multidrug resistant Gram-negative infections and drug-induced toxicity is considered as the main obstacle for using this valuable antibiotic. RESULTS: In total, 30 articles, including 29 animal studies and one clinical trial were included in this study. These compounds, including aged black garlic extract, albumin fragments, alpha lipoic acid, astaxanthin, baicalein, chrysin, cilastatin, colchicine, curcumin, cytochrome c, dexmedetomidine, gelofusine, grape seed proanthocyanidin extract, hesperidin, luteolin, lycopene, melatonin, methionine, N-acetylcysteine, silymarin, taurine, vitamin C, and vitamin E exhibited beneficial effects in most of the published works. CONCLUSIONS: In this review, the authors have attempted to review the available literature on the use of several compounds for prevention or attenuation of colistin-induced nephrotoxicity. Most of the studied compounds were potent antioxidants, and it seems that using antioxidants concomitantly can have a protective effect during the colistin exposure.

The experience and outcomes of multidisciplinary clinical pharmacist-led parenteral nutrition service for individuals with intestinal failure in a center without home parenteral nutrition.

BACKGROUND/OBJECTIVES: Intestinal Failure (IF) is a rare but serious form of organ failure, and patients with IF are dependent on Total Parenteral Nutrition (TPN) to maintain growth and development. This study aimed to describe the experiences of a multidisciplinary clinical pharmacist-led TPN service in the Intestinal Rehabilitation Unit of Shiraz Organ Transplant Center. SUBJECTS/METHODS: This prospective study was conducted in Shiraz Organ Transplant Center, Iran from February 2018 to October 2020, including seven months with and 24 months without the clinical pharmacist involvement. Clinical and nutritional outcomes as well as the potential complications of TPN were compared in these two periods. RESULTS: This study was conducted on 107 patients. The most important complication occurred among the patients receiving TPN were catheter infection (42.05%), sepsis, and catheter thrombosis (18.69%). Portal vein thrombosis (OR = 26.56) and length of Intensive Care Unit (ICU) stay (OR = 1.12) were significantly associated with the rate of parenteral nutrition-associated liver disease. The results also revealed an association between the rate of sepsis and history of malignancy, catheter thrombosis, length of the small bowel, length of PN, length of hospital stay, and length of ICU stay. Moreover, the results showed a significant difference regarding the patients' outcomes and TPN complications before and after the clinical pharmacist interventions (P < 0.05). CONCLUSION: Working as a multidisciplinary team in Intestinal Rehabilitation Unit (IRU) has been suggested to improve patients' outcomes and reduce mortality and morbidity. Presence of a clinical pharmacist in this team can help improve the TPN service provided for individuals with IF.

A Survey of Medical Residents' Knowledge, Attitude, and Practice about Drug-Drug Interactions, Shiraz, Iran.

Rationale, aims and objectives: Medical residents are among the most important and influential members of the medical team and the level of their knowledge regarding potential drug-drug interactions (DDIs) is a good predictor of the ability to prevent the occurrence of DDIs, as well as safe and rational prescribing in inpatient settings. This survey was designed to evaluate internal medicine and cardiology residents' knowledge and opinion toward DDIs and to determine different sources of DDI information used by this population. Method: This cross-sectional knowledge attitude practice (KAP) questionnaire study was conducted in Shiraz, Iran. A 25-question questionnaire was designed and completed by 86 internal medicine and cardiology residents. The questions were related to the participants' demographic information, their practice characteristics, the information sources used by the participants, the residents' opinion regarding DDIs, and their knowledge regarding the interaction between 8 drug pairs. Results: The results showed that when the participants wanted to learn more about DDIs, most of them used software on mobile or tablet (59.3%). Nearly three-fourths of the participants (73.82%) reported that when a patient was about to be exposed to a potential DDI, they were informed by software on mobile or tablet that the interaction may be present. On average, residents answered 44.03% ± 23.79 of drug pair questions correctly.Conclusion: Our results show insufficient practice skills, as well as relatively poor knowledge concerning the participants' answers to questions. It seems that further practical training and education are required to enable prescribers to prevent potential DDIs.

Affordability of Medication Therapy in Diabetic Patients: A Scenario-Based Assessment in Iran's Health System Context.

BACKGROUND: Diabetes imposes an enormous burden on patients, families, societies, and healthcare systems. Determining the affordability of medications is an important complicated and vague task, especially in low- and middle-income countries (LMICs). This study aimed to assess the affordability of diabetes medication therapy in Iran's health system. METHODS: This paper presents a scenario-based assessment of the affordability of all registered anti-diabetes medications in Iran in 2017. To this end, 4 medication therapy scenarios were defined as mono, dual, triple, and insulin therapy in accordance with the existing guidelines and clinicians' opinions. Then the affordability ratio of each treatment scenario was determined for type 1 and type 2 diabetes drawing on the World Health Organization (WHO)/Health Action International (HAI) Methodology. If the affordability ratio for treatment schedules was more than 1, the patients' out-of-pocket (OOP) expenses exceeded the lowest-paid unskilled government worker (LPGW)' wage per day, and the treatment was labelled as non-affordable. RESULTS: The results revealed that the mono, dual, and triple (non-insulin) medication therapies in type 2 diabetes were affordable, despite an increase in the dosage or a switch from the monotherapy to the combination therapy of oral medications. However, some treatment scenarios in the triple therapy, including oral plus insulin and some insulin only therapies, were proved to be non-affordable. In type 1 diabetes, only insulin glulisine, detemir, and lispro were non-affordable in monotherapy. Regarding the combination therapy, only isophane insulin with aspart or regular insulin were affordable treatments. CONCLUSION: Although oral medication therapies were documented to be affordable, insulin therapy, with current coverage conditions, for patients with lowest paid wages and those receiving even less is unaffordable and a major barrier to treatment; hence, policy-maker should consider targeting and more financial protection policies to improve the affordability of insulin therapies among this group of patients.

Drug-induced liver injury in Switzerland: an analysis of drug-related hepatic disorders in the WHO pharmacovigilance database VigiBase from 2010 to 2020.

AIMS OF THE STUDY: Our aim was to explore drug-induced liver injury (DILI) in Switzerland using the real-world data of the global pharmacovigilance database VigiBaseÔ, with a special focus on the new drug class of checkpoint inhibitors. This is the first study investigating drug-related hepatic disorders in Switzerland in a global pharmacovigilance database. METHODS: This was a retrospective study analysing the ICSRs (individual case safety reports) of the global pharmacovigilance database VigiBaseÔ. We explored all ICSRs submitted in Switzerland within the last 10 years (1 July 2010 to 30 June 2020). For data extraction, the standardised MedDRA query (SMQ) “narrow drug-related hepatic disorders – severe events only” was applied. The ICSRs, drug-reaction pairs and adverse drug reactions were analysed descriptively, including a special focus on checkpoint inhibitors. For comparing the hepatic adverse drug reactions of pembrolizumab, nivolumab and ipilimumab, the reporting odds ratios (RORs) were calculated in a disproportionality analysis. RESULTS: In total, 2042 ICSRs could be investigated, comprising 10,646 drugs and 6436 adverse drug reactions. Gender was equally distributed between male and female. Patients were on average 57 years old. The mortality rate was high, with fatal adverse reactions in over 10% of cases. On average, patients used five drugs including two suspected drugs. Paracetamol, amoxicillin/clavulanic acid, esomeprazole and atorvastatin ranked among the most frequently suspected drugs for severe drug-related hepatic disorders. However, VigibaseÔ data are not appropriate for judging causality and these results should be interpreted with caution owing to the possible influences of comedication or comorbidity. An average of three adverse drug reactions per ICSR were reported, most frequently including hepatocellular injury, cholestatic liver injury, and liver injury. For checkpoint inhibitors, hepatitis was the most frequently reported hepatic adverse drug reaction. In comparison with nivolumab and ipilimumab, pembrolizumab had a significantly higher ROR for hepatitis (2.41, p = 0.016), but also a lower ROR for autoimmune hepatitis (0.11, p = 0.009). CONCLUSION: Our findings highlight the importance for healthcare providers in Switzerland to pay special attention to possible drug-induced liver injuries because of their high mortality rate. The analysis of real-world data confirms the previous assumption that hepatitis is the most frequent hepatic adverse event for checkpoint inhibitors. Further clinical studies are warranted to directly compare hepatic adverse drug reactions to different checkpoint inhibitors.

The effect of silymarin on liver enzymes and antioxidant status in trauma patients in the intensive care unit: a randomized double blinded placebo-controlled clinical trial.

AIM OF THE STUDY: This study was conducted to investigate the positive effect of silymarin on liver enzymes and antioxidant status in trauma patients with elevated liver enzymes due to trauma-induced liver injury, admitted to the intensive care unit. MATERIAL AND METHODS: This one-year, randomized, double-blinded, placebo-controlled clinical trial was conducted on 90 trauma patients. The participants were assigned to either receiving Livergol tablets containing 140 mg of silymarin or 140 mg of placebo three times daily for 14 days. Liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), were measured at baseline and days 3, 7, 9 and 14 after intervention. Also, antioxidant markers were measured at baseline and day 14 after treatment. RESULTS: Receiving silymarin supplement significantly lowered the liver enzymes, compared to placebo (p < 0.05). The mean serum level of malondialdehyde (MDA) was significantly decreased and the mean serum levels of total antioxidant capacity (TAC) and thiol groups were significantly increased in the silymarin group from baseline to day 14. In the placebo group, mean serum levels of MDA and thiol groups were significantly increased, while serum level of TAC was not significantly changed at day 14, compared to baseline. Also, the mean serum level of MDA was significantly lower, while the serum levels of thiol groups and TAC were significantly higher in the silymarin group. CONCLUSIONS: Silymarin supplementation significantly improved some antioxidant markers (TAC and thiol) and decreased liver enzymes in patients with trauma-induced liver injury.

Assessing the Performance of Community Pharmacies in Iran by Measuring Responsiveness to Non-Medical Needs: An Application of WHO Responsiveness Framework.

OBJECTIVE: Despite growing debates about the health systems' nonmedical performance, there has not been any empirical research on nonmedical performance and patients' rights consideration as a driver of human rights in the pharmaceutical sector. This study's main objective was to assess the nonmedical performance of community pharmacies of Shiraz, Iran. METHODS: A cross-sectional study was conducted using two self-administrated Likert-based questionnaires based on the World Health Organization (WHO) responsiveness framework and the legal charter communicated by the Ministry of Health and Medical Education of Iran. The population was patients older than 18 years who took a prescription from community pharmacies located in Shiraz and willing to answer the questions voluntarily, from 2018 to 2019. Considering the weights of subdimensions of responsiveness provided by the WHO framework, the total score of responsiveness was calculated ranging from 0 to 100. FINDINGS: The response rate was 80.5%. The mean (standard deviation) overall score of responsiveness was 57.18 (21.61), with a median of 56.71. The mean score of client orientation was lower in respondents with a high education level than those with a diploma and under diploma (P = 0.028). CONCLUSION: Nonmedical pharmacy performance was considered either medium or high in more than half of the cases based on the participants' views. Regarding client, orientation was seen less often in patients with high education level compared to those with a lower education level.

Association between Serum Vitamin D Concentration Status and Matrix Metalloproteinase-9 in Patients Undergoing Elective Percutaneous Coronary Intervention.

Cardiovascular diseases (CVD) have become increasingly life-threatening during recent decades. Several studies have shown that matrix metalloproteinase-9 (MMP-9) plays an important role in the process of atherosclerosis and heart remodeling. On the other hand, Vitamin D deficiency has been recognized as a risk factor for CVD. According to the prevalence of vitamin D deficiency in our country, Iran, we aimed to evaluate the relationship between vitamin D status and the level of MMP-9 in patients undergoing percutaneous coronary intervention. In this prospective cross-sectional study, the patients who were candidates for elective coronary angioplasty were included. Baseline serum MMP-9 and vitamin D levels were measured before intervention. The patients were categorized into three groups: Vitamin D-severely deficient (≤ 10 ng/mL), vitamin D-moderately deficient (11-20 ng/mL), and vitamin D-insufficient/sufficient (> 21 ng/mL). Totally, 150 patients were assessed. The analysis showed that serum MMP-9 levels were higher in patients with lower vitamin-D concentrations. A significant inverse correlation was found between MMP-9 concentration and 25 (OH) vitamin D level (P = 0.039). According to our results, it may be concluded that low levels of vitamin D may lead to more vulnerable atherosclerotic plaques and consequently more cardiovascular adverse effects in post-PCI patients.

Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen.

The 2019 novel coronavirus disease (COVID-19) was first detected in Wuhan, Hubei Province, China, in late 2019. Since then, COVID-19 has spread to more than 200 countries in the world, and a global pandemic has been declared by the World Health Organization (WHO). At present, no vaccines or therapeutic regimens with proven efficacy are available for the management of COVID-19. Hydroxychloroquine/chloroquine, lopinavir/ritonavir, ribavirin, interferons, umifenovir, remdesivir, and interleukin antagonists, such as tocilizumab, have been recommended as potential treatment options in COVID-19. Transplant patients receiving immunosuppressant medications are at the highest risk of severe illness from COVID-19. At the same time, with regard to receiving polypharmacy and immunosuppressants, treatment options should be chosen with more attention in this population. Considering drug-drug interactions and adverse effects of medications used for the treatment of COVID-19, such as QT prolongation, the dose reduction of some immunosuppressants or avoidance is recommended in transplant recipients with COVID-19. Thus, this narrative review describes clinically important considerations about the treatment of COVID-19 and immunosuppressive regimens regarding modifications, side effects, and interactions in adult kidney or liver allograft recipients.

The effect of different intensivist staffing patterns on the rate of potential drug-drug interactions in adult trauma intensive care units.

BACKGROUND: Drug-drug interactions (DDIs) have created alarming challenges for public health, especially in those admitted to intensive care units (ICUs). Many studies have shown that involvement of intensivists in the ICUs improves the outcome and decreases the treatment costs. The effect of academic versus non-academic (therapeutic) intensivist as well as hours of coverage and attendance of intensivist on potential DDIs (pDDIs) was evaluated in six adult trauma ICUs of a level one trauma center. METHODS: In this 6-month cross-sectional study, 200 patients were included. The DDIs were classified into five groups, including type A, B, C, D, and X. pDDIs were defined as interactions belonged to C, D and X categories. Patients in six adult ICUs with three different patterns of intensivist staffing models including type A (once-daily therapeutic intensivist visit followed by 24 h on-call), B (twice-daily academic intensivist visit, 8 h of attendance in ICU and 16 h on-call) and C (all criteria just like ICU type B, except for the presence of therapeutic instead of academic intensivist) were screened for pDDIs. RESULTS: In total, 3735 drug orders and 3869 drugs (193 different types) were screened and 1826 pDDIs were identified. Type C, D and X interactions accounted for 60.6%, 35.5%, and 3.9% of all pDDIs, respectively. The mean of pDDI per patient was significantly higher (p-value < 0.001) in the ICU type A than ICU types C and B. The frequency of pDDIs was the highest in the type A ICUs. A statistically significant relationship was observed between the number of prescribed drugs and ICU length of stay (p-value < 0.001 and p = 0.009, respectively). CONCLUSION: Different patterns of intensivist staffing affect pDDIs to varying degrees. In the studied ICUs academic versus therapeutic intensivist, twice versus once-daily visit, and 8 h attendance with16 h on-call versus 24 h on-call were associated with more reductions in pDDIs. PLAIN LANGUAGE SUMMARY: The impact of different intensivist staffing patterns in ICUs on the rate of potential drug-drug interactionsDrug-drug interactions (DDIs) have created alarming challenges for public health, especially in patients admitted to intensive care units (ICUs). Many studies have shown that involvement of intensivists in the ICUs improves the outcome and limits the costs. Considering the high incidence of potential DDIs (pDDIs) occurring for critically ill patients and the importance of ADRs caused by pDDIs in ICUs, the effect of the presence of an academic versus therapeutic intensivist, as well as the hour of coverage of intensivist on prevalence of pDDIs was evaluated in six adult trauma ICUs of a level one trauma center in Shiraz, Iran. We also determined the prevalence of pDDIs and their associated risk factors. To the best of our knowledge, this is the first study that has assessed the effect of various ICU physician staffing models on the incidence and pattern of pDDIs.

The Efficacy and Safety of Low Dose versus Usual Dose of Hyoscine During Endoscopic Retrograde Cholangiopancreatography: A Randomized Clinical Trial.

PURPOSE: To evaluate the efficacy and safety of low dose versus usual dose of Hyoscine during endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: This randomized, open-label clinical trial included 282 patients undergoing ERCP who had duodenal peristalsis interfering with cannulation. Patients were randomly divided into two groups: Group one and two received low (5 mg) and usual (10 mg) dose of Hyoscine, respectively. Cardiovascular service consultation was performed for all patients before entering the study and performing ERCP. Hyoscine was injected intravenously, and the spasmolytic effect of the drug was assessed while the papilla was in a completely enface view. The time interval between cessation of peristalsis and its further onset was recorded by the chronometer. Also, patient's heart rate and blood pressure were monitored during ERCP by digital monitoring. RESULTS: The results showed no statistically significant differences in the mean duration of peristalsis, the duration of the antispasmodic activity and the time required to increase the heart rate between two groups (P=0.38, P=0.48, P=0.32, respectively). No significant differences were observed regarding the average of heart rate and mean arterial blood pressure (MAP) before drug administration between the two groups (P=0.182 and P=0.29, respectively), but after the drug administration, tachycardia and hypotension were significantly higher in the second group (P=0.007 and P=0.001, respectively). There was no statistically significant difference in the frequency of arrhythmia between two groups (P=0.08). The results also showed that tachycardia and hypotension occurred more frequently in men and elderly patients (P <0.05). CONCLUSION: A low dose of Hyoscine is as effective as the usual dose and its side effects such as alteration in blood pressure and heart rate are much fewer, especially in men and elderly patients.

Effect of mirtazapine on pruritus in patients on hemodialysis: a cross-over pilot study.

BACKGROUND: Uremic pruritus (UP) is a highly prevalent and disturbing problem in patients with advanced chronic kidney disease (CKD); however, treatment of UP is largely unsatisfactory. The present study was designed to investigate the effectiveness of mirtazapine, an atypical antidepressant agent with potent antagonistic activity against serotonin (5HT2, 5HT3) and histamine (H1) receptors, in the treatment of pruritus in hemodialysis (HD) patients. METHODS: An 8-week long, prospective, open-label, and cross-over randomized clinical trial study was conducted on 77 HD patients with chronic pruritus. After a 2-week washout period, eligible patients were randomly assigned either to the mirtazapine (15 mg per day) or gabapentin (100 per day) for 2 weeks. Following 2 weeks washout period, subjects crossed over to the other treatment arm for 2 more weeks. The severity of pruritus was measured seven times during each treatment period using the visual analogue scale (VAS). Furthermore, at the end of the study, patients also were blindly asked which treatment (first or last in the sequential course of the study) they preferred. RESULTS: Sixty-one patients completed two treatment periods of the study. Although, compared to baseline, both gabapentin and mirtazapine treatment resulting in significant improvement in VAS scores, decreasing in pruritus severity was significantly greater in the mirtazapine treatment period compared with the gabapentin treatment period (P < 0.001). Furthermore, although side effects such as drowsiness and dry mouth more reported in the mirtazapine treatment period, overall higher percentage of the study patients preferred mirtazapine over gabapentin for the treatment of their pruritus symptoms. CONCLUSIONS: Although preliminary, our study provides evidence that mirtazapine can be an effective therapy for UP in patients who are on maintenance HD. However, further studies would be necessary to confirm effectiveness as well as the safety of mirtazapine in the long-term management of chronic pruritus.

Types and outcomes of cytopenia in critically ill patients.

Cytopenia is common complication in critically ill patients. Aim: Incidence and pattern of different types of cytopenia as well as its impact on mortality and length of stay in critically ill patients were evaluated. Methods: Critically ill patients with any kind of cytopenia for more than 2 days were evaluated. Results: Anemia was the most common type of cytopenia in the patients (99.14%), followed by lymphocytopenia (32.17%), thrombocytopenia (27.82%), and leukopenia (19.13%). Mortality rate was significantly higher in patients with anemia (p < 0.0001), thrombocytopenia (p < 0.0001), leukopenia (p < 0.0001), neutropenia (p = 0.004), lymphopenia (p = 0.002) and pancytopenia (p < 0.0001). Higher duration of anemia, lymphopenia and thrombocytopenia were associated with longer intensive care unit stay (p < 0.0001, p < 0.0001 and p < 0.001, respectively). Conclusion: Among all assessed variables, incidence of thrombocytopenia could independently predict the mortality.