Unintended consequences: Hypotonic serum-induced acute kidney injury in shoulder arthroscopy.

Arthroscopic shoulder surgery is an orthopaedic technique that involves the use of normal saline or hyperosmolar serums as irrigation. The mentioned operation is commonly regarded as a safe medical intervention. Occasionally, it may have serious repercussions for the patient. Fluid extravasation into muscle tissues and tissue injury and instability are possible consequences. This can be affected by the type and amount of serum used and the length of the surgery. The objective of this study was to document four cases of shoulder arthroscopy in which sterile distilled water, wrongly labelled as irrigation fluid, was utilized during the surgical procedure. Patients were readmitted a week after discharge due to acute kidney injury symptoms like fatigue and lethargy. All four patients were released after haemodynamic stability and normalization after haemodialyses. Due to the incident, serums should be closely monitored and labeled for the safety of patients. Additionally, distilled water as an irrigation solution in arthroscopic surgeries can harm patients. Although normal saline and hyperosmolar serums are unavailable, this remains true. LEVEL OF EVIDENCE: Level IV.

Taurine in Septic Critically Ill Patients: Plasma versus Blood.

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.

Incremental Healthcare Resource Utilization and Expenditures Associated with Cardiovascular Diseases in Patients with Diabetes: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease (CVD) is the most prevalent comorbid condition among patients with diabetes. The objective of this study is to determine the incremental healthcare resource utilization and expenditures (HRUE) associated with CVD comorbidity in diabetic patients. METHODS: In a cross-sectional study, patients receiving antidiabetic drugs were identified using the 2014 database of the Iran Health Insurance Organization of East Azerbaijan province (Iran). The frequency of HRUE was the main outcome. Outcome measures were compared between diabetic patients with and without CVD comorbidity during 2014-2016. The generalized regression model was used to adjust for cofounders because of a highly skewed distribution of data. Negative binomial regression and gamma distribution model were applied for the count and expenditure data, respectively. RESULTS: A total of 34,716 diabetic patients were identified, of which 21,659 (63%) had CVD comorbidity. The incremental healthcare resource utilization associated with CVD compared to non-CVD diabetic patients for physician services, prescription drugs, laboratory tests, and medical imaging was 5.9±0.34 (28% increase), 46±1.9 (46%), 12.9±0.66 (27%), and 0.16±0.40 (7%), respectively (all P<0.001). Similarly, extra health care costs associated with CVD comorbidity for physician services, prescription drugs, laboratory tests, and medical imaging were 10.6±0.67 million IRR (294.4±18.6 USD) (50% increase), 1.44±0.06 million IRR (40±1.6 USD) (32%), 8.36±0.57 million IRR (232.2±15.8 USD) (58%), 0.51±0.02 million IRR (14.1±0.5 USD) (24%), and 0.29±0.02 million IRR (8±0.5 USD) (22%), respectively (all P<0.001). CONCLUSION: CVD comorbidity substantially increases HRUE in patients with diabetes. Our findings draw the attention of healthcare decision-makers to proactively prevent CVD comorbidity in diabetic patients.

Detection of subclinical nephrotoxicity induced by aminoglycosides in critically ill elderly patients using trough levels and urinary neutrophil gelatinase-associated lipocalin.

OBJECTIVES: Early detection of aminoglycoside-induced acute kidney injury (AKI) is crucial in intensive care unit (ICU) patients, but it is not adequately reflected by serum creatinine (SrCr) levels. This study proposed investigating the relationship between amikacin trough levels and the development of nephrotoxicity using both conventional markers and a new biomarker of renal function in critically ill elderly patients. METHODS: Thirty-three critically ill patients aged ≥65 years with normal SrCr who received once-daily amikacin were evaluated. Trough levels of amikacin, creatinine clearance (CrCL) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were measured during the 10-day study period. The patients were divided into three groups and were compared based on the trough levels on both day 3 and day 7: <3 µg/mL (low trough (LT)), 3-6 µg/mL (moderate trough (MT)) and >6 µg/mL (high trough (HT)). RESULTS: In the LT group, neither CrCL nor uNGAL levels significantly changed from baseline (p=0.364 and p=0.562, respectively). In the MT group, the CrCL level altered significantly over time from baseline (p=0.007), but the uNGAL level did not change significantly over the study period (p=0.916). In the HT group, both CrCL and uNGAL levels significantly changed from baseline during the study period (p=0.002 and p=0.046, respectively). CONCLUSIONS: In critically ill elderly patients with MT, the mean uNGAL level changed at least 4 days earlier than the SrCr level. Instead, the trough level of amikacin demonstrated a potential value for predicting subclinical AKI for implementing necessary interventions. Amikacin trough levels <3 µg/mL in the once-daily dosing regimen appeared safe, even in geriatric patients. Further studies are needed to confirm this finding.

Efficacy of furosemide-albumin compared with furosemide in critically ill hypoalbuminemia patients admitted to intensive care unit: a prospective randomized clinical trial.

BACKGROUND: Some physicians co-administer albumin with loop diuretics to overcome diuretic resistance in critically ill hypoalbuminemia patients, though previous studies have reported conflicting results on this matter. OBJECTIVE: The effects of adding albumin to furosemide to enhance its efficacy in critically ill hypoalbuminemia patients are evaluated. METHODS: This was a non-blinded randomized trial. 49 adult critically ill patients with hypoalbuminemia and generalized edema who received randomly furosemide and furosemide/albumin complex were enrolled. The patients' urine was collected at intervals of 2, 4, 6 and 8 h after initiation of the furosemide treatment, and the urine output and urinary excretion of furosemide and sodium were measured. The urinary excretion of furosemide was considered an indicator of drug efficacy. RESULTS: The amount of sodium and furosemide excreted in urine showed no significant differences between the two groups; however, the mean of the urinary excretion of furosemide in the first 2 h after drug infusion was significantly higher (p = 0.03) in the furosemide/albumin group. No significant correlation between APACHE II scores and serum albumin levels and the urinary excretion of furosemide was seen. CONCLUSION: The results indicated that there is not statistically significant differences between groups with furosemide alone and combined with albumin in urinary furosemide excretion. It seems that adding albumin for furosemide pharmacotherapy regime is not recommended as an intervention to increase furosemide efficacy in critically ill hypoalbuminemia patients. TRIAL REGISTRATION: IRCT with the registration number IRCT201412132582N12 in 23 February 2015; https://en.irct.ir/trial/2356 Graphical abstract.

Effect of Adding Insulin Glargine on Glycemic Control in Critically Ill Patients Admitted to Intensive Care Units: A Prospective Randomized Controlled Study.

OBJECTIVE: We aimed to examine the effects of adding a longer-acting insulin glargine to existing glucose control on reducing blood-glucose fluctuations in an intensive care unit (ICU). METHODS: A total of 110 patients randomly received adjuvant insulin glargine 15 IU/day (glargine) or placebo (control), in addition to daily infusion of insulin to maintain glucose levels at a target of 140-180 mg/dL. End points were mean and variance of blood glucose and frequency of hypoglycemia, hyperglycemia, ICU stay, and mortality. Data were analyzed with repeated-measures ANOVA and Mann-Whitney U test. RESULTS: Average daily glucose level was significantly less in the glargine group than controls (P<0.0001), while there was no difference in daily variance in blood glucose between the two groups. The duration of glucose concentrations being within the target range was identical between the glargine and control groups (16.6±4.9 vs 16.4±4.6 hours/day, P=0.844) during the 7 days of admission. The frequency of hypoglycemia was greater in the glargine group and total duration of hyperglycemia (>180 mg/dL) much longer among controls (P<0.001). Similar mortality rates were observed in both groups, while ICU length of stay was 2 days shorter in the glargine group. CONCLUSION: Addition of insulin glargine to routine protocols more effectively reduces glucose levels and decreases incidence of hyperglycemic episodes and regular insulin usage. This adjustment may be associated with decreases in duration of ICU stay or increases in hypoglycemic events.

Effect of gastric residual volume monitoring on incidence of ventilator-associated pneumonia in mechanically ventilated patients admitted to intensive care unit.

OBJECTIVES: The value of gastric residual volume (GRV) monitoring in ventilator-associated pneumonia (VAP) has frequently been questioned in the past years. In this trial, the effect of GRV on the frequency of VAP was evaluated in critically ill patients under mechanical ventilation. METHODS: This descriptive study was carried out on 150 adult patients admitted to the intensive care unit over a 14-month period, from October 2015 to January 2017. GRV was measured every three hours, and gastric intolerance was defined as GRV>250 cc. The incidence of vomiting and VAP, GRV, length of mechanical ventilation and ICU stay, APACHE II and SOFA scores, and mortality rate were noted. RESULTS: The mean APACHEII and SOFA scores, ICU length of stay, and duration of mechanical ventilation in the GRV>250ml group were significantly higher than in the GRV≤250 ml group (P<0.05). Also, a significantly higher number of patients in the GRV>250ml group experienced infection (62.3%) and vomiting (71.7%) compared with the GRV≤250 group (P<0.01). The highest OR was observed for SOFA score >15 and APACHE II >30, which increased the risk of GVR>250 ml by 10.09 (1.01-99.97) and 8.78 (1.49-51.58), respectively. Moreover, the increase in GVR was found to be higher in the non-survivor than in the survivor group. CONCLUSION: Increased GRV did not result in increased rates of VAP, ICU length of stay, and mortality. Therefore, the routine measurement of GRV as an important element of the VAP prevention bundle is not recommended in critically ill patients.

Arterial vs venous lactate: Correlation and predictive value of mortality of patients with sepsis during early resuscitation phase.

PURPOSE: To compare the lactate concentrations obtained from venous to those obtained from arterial blood in predicting hospital mortality of patients with sepsis and septic shock. To also assess lactate clearance as predictor for mortality. METHODS: 100 patients with septic shock were prospectively enrolled. Serum was sampled at baseline and after 6 h of resuscitation from arterial and venous lines. Demographic, severity indices, hemodynamic measures as well as lactate clearance levels were noted. Data were analyzed for bias and precision. RESULTS: There was correlation between venous and arterial lactate concentrations at the baseline (R = 0.68) and at the 6-hour time point (R = 0.95). Venous concentrations were consistently higher than those obtained from an arterial access by 0.684 mg/dL. Further, arterial lactate level > 3.2 mmol/L and clearance of <20% were considered the cutoff for the mortality risk. While only 8% of the patients with no risk died, all 20 patients who had lactate level > 3.2 mmol/L and clearance of <20% died within the hospital. CONCLUSION: Our data suggests a strong correlation between arterial and peripheral venous the lactate levels and in the initial phase of resuscitation in septic shock patients we can use venous lactate level as biomarker instead of arterial lactate level. The study also showed that combining lactate levels and its clearance is a reliable predictor of mortality in sepsis.

A 4-Year Investigation of Ambulatory Health Care Expenditure Concentration and High-Cost Patients: An Experience From a Developing Country.

The aim of this study is to investigate the concentration of ambulatory health care expenditure in a large Iranian outpatient population. This study used 2013-2016 individual-level claims data of Iranian Health Insurance Organization in East Azerbaijan province. All ambulatory care utilizers were included in the study. We determined characteristics and utilization pattern of high-cost patients as well as their predictors. A total of 1 128 149 patients were included. The top 10% of patients accounted for 62.56% of the total expenditure. This skewed expenditure pattern remained relatively stable over the study period. Female sex, older age, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes increase the odds of being high cost.

Epidemiology of multimorbidity in Iran: An investigation of a large pharmacy claims database.

PURPOSE: Multimorbidity (MM) (presence of more than one chronic condition within a same patient) imposes a heavy burden on patients and health care systems. In contrast to high-income countries, the epidemiology of this phenomenon is unclear in low- and middle-income countries, particularly among Iranian population. METHODS: This was a retrospective cohort study using Iranian Health Insurance Organization claims database. A framework was developed for identifying a set of 18 chronic conditions from the pharmacy claims data in Iran. All 2013 outpatient utilizers (aged 18 years or older) were included. Data were analyzed according to number of chronic conditions, gender, and age. The association between MM and utilizations of health services was examined for 2013 to 2016. RESULTS: In total, 481 733 people were included. Cardiovascular diseases (including hypertension) (19.1%), depression/anxiety/sleep disorders (13.7%), and acid-related disorders (10.3%) were the three most prevalent conditions. MM was present in 21.1%. Although prevalence of MM is higher in older age groups and was present in 40% of individuals aged 65 and older, the absolute number of multimorbid patients was higher in those younger than 65 years (66 271 vs 35 386). MM was more prevalent among women (22.1%) compared with men (19.5). After multivariate adjustment for age group and sex, each additional chronic condition was associated with an increase of 2.23 physician visits, 2.86 drugs dispensed, 2.32 laboratory tests, and 1.6 medical imaging. CONCLUSIONS: Our findings challenge the current single-disease-based assumption implicit in Iranian health care system. To take account of MM, complementary strategies should be designed and implement in health care system.

The Relationship of Serum Vitamin D Level With the Outcome in Surgical Intensive Care Unit Patients.

The aim of this study was to assess the correlation of serum vitamin D with ICU length of stay, mortality rate, length of mechanical ventilation, and incidence of sepsis. We conducted a descriptive analytic study on 793 patients admitted to surgical ICU wards in northwest of Iran from March 2015 to March 2016. Patients were assessed during the ICU stay and the following data were collected: Glasgow Coma Score (GCS), APACHE II score, incidence of sepsis, duration of mechanical ventilation, LoS, mortality rate, and laboratory data (such as serum vitamin D, calcium, phosphorus, etc). The effect of vitamin D deficiency and the confounding factors on length of stay was assessed using the multinomial regression. Of 793 patients, 161 patients (20.3%) were in vitamin D deficiency group, 306 (38.6%) in vitamin D insufficiency group, 326 (41.1%) in vitamin D sufficiency group. Vitamin D deficiency increased risk of sepsis (OR = 22.93; 95%CI: 10.631-49.78) and mortality rate (OR = 42.93; 95%CI: 15.2-121.22). Vitamin D deficiency/insufficiency is a result of chronic and severe comorbidities of patients and can be considered as a helper but not a real risk factor for mortality and its level should be assessed in surgical critically ill patients. The way that various levels of vitamin D impact outcome in critically ill patients remains to be elucidated and further multi-center trials are needed to validate our results.

The Effect of Intravenous Selenium on Oxidative Stress in Critically Ill Patients with Acute Respiratory Distress Syndrome.

OBJECTIVE: To modulate the inflammatory response in respiratory distress syndrome (ARDS) with selenium. BACKGROUND: Selenium replenishes the glutathione peroxidase proteins that are the first line of defense for an oxidative injury to the lungs. METHODS: Forty patients with ARDS were randomized into two groups: the SEL+ group being administered sodium selenite and the SEL- group receiving normal saline for 10 days. Blood samples were taken on Day-0, DAY-7, and Day-14 for assessment of IL-1 beta, IL-6, C-reactive protein, GPx-3, and selenium. Ferric reducing antioxidant power (FRAP) was measured in the bronchial wash fluids. Pearson correlation and repeated measure analysis were performed to examine the effects of selenium on the inflammatory markers. RESULTS: Sodium selenite replenished selenium levels in the SEL+ group. Selenium concentrations were linearly correlated to serum concentrations of GPx3 (R value: 0.631; P < 0.001), and FRAP (R value: -0.785; P < 0.001). Serum concentrations of both IL 1-beta (R value: -0.624; P < 0.001) and IL-6 (R value: -0.642; P < 0.001) were inversely correlated to the serum concentrations of selenium. There was a meaningful difference between two groups in airway resistance and pulmonary compliance changes (P values 0.008 and 0.028, respectively). CONCLUSION: Selenium restored the antioxidant capacity of the lungs, moderated the inflammatory responses, and meaningfully improved the respiratory mechanics. Despite these changes, it had no effect on the overall survival, the duration of mechanical ventilation, and ICU stay. Selenium can be used safely; however, more trials are essential to examine its clinical effectiveness.

Effect of a Probiotic Preparation on Ventilator-Associated Pneumonia in Critically Ill Patients Admitted to the Intensive Care Unit: A Prospective Double-Blind Randomized Controlled Trial.

BACKGROUND: Ventilator-associated pneumonia (VAP) occurs as a life-threatening complication in critically ill mechanically ventilated patients. Probiotic administration may modify the gut microbiota; however, whether this modification could decrease VAP occurrence is not known. METHODS: In this study, 100 adult critically ill patients undergoing mechanical ventilation for >48 hours were randomly assigned to either the probiotic or the control group. The patients in the probiotic group received 2 capsules of probiotic preparation containing Lactobacillus, Bifidobacterium, and Streptococcus spp., and those in the control group received placebo daily for 14 days. RESULTS: The patients in the probiotic group had a lower incidence of statistically microbiologically confirmed VAP. The duration of intensive care unit (ICU) and hospital stay was also lower in the probiotic group (P < .05). More than half of the patients in the control group had gastric residuals during ICU stay, compared with only 30% of patients in the probiotic group (P = .004). Probiotic usage led to a nonsignificant decrease in diarrhea, gastric and oropharyngeal colonization, and incidence of multidrug-resistant pathogens. The Kaplan-Meier survival curves for time to the first episode of VAP did not show a significant difference between probiotic and control groups (log-rank test = 1.89; P = .17). CONCLUSIONS: The results of probiotic administration for the prevention of VAP remain inconclusive in this trial. However, such an approach can decrease the length of ICU and hospital stay. Well-designed multicenter clinical studies with defined combinations of probiotics and definite end points are necessary in this field.

Effect of Cucurbita Maxima on Control of Blood Glucose in Diabetic Critically Ill Patients.

Purpose: Cucurbita maxima Duchense (C. maxima) has been widely used in China and Mexico as a hypoglycemic plant for controlling blood glucose in diabetic patients. Furthermore, in northwest of Iran, this plant is used traditionally for controlling of diabetes. We examined the effect of C. maxima pulp besides insulin on control of hyperglycemia in diabetic patients admitted to Intensive care unit (ICU). Methods: Twenty critically ill patients who were admitted to the ICU were enrolled in this study. 5g lyophilized powder of C. maxima was administrated every 12 hours for 3 days. Moreover, blood glucose level and insulin dose were measured every 1-4 hours during 3 days before administration and 3days at the time of C. maxima administration. Results: The average of glucose level in 3 days before C. maxima administration was 214.9 ± 55.7 mg/dl, while in 3 days during C. maxima administration it was decreased to 178.4 ± 36.1 mg/dl (P<0.001). Additionally, the average insulin dose during 3 days before intervention was 48.05 ± 36.5 IU and during the 3 days of C. maxima administration was decreased to 39.5 ± 27.8 IU (P=0.06). Conclusion: It seems that C. maxima may decrease high blood glucose level fast and effective in diabetic critically ill patients.

Association Between Disease Severity and Calcium Concentration in Critically Ill Patients Admitted to Intensive Care Unit.

BACKGROUND: Hypocalcemia is very common in critically ill patients admitted to ICU. However, its clinical importance and relation to patient's outcome during early days of ICU admission is questionable. Based on the mentioned problem, it seems that calcium assessment is highly important in these patients. The present study aimed at evaluating the relationship between different calcium concentrations (total/ionized/corrected) and disease severity in critically ill patients. METHODS: A total of 100 patients admitted to intensive care units of Imam Reza and Shohada hospitals during Feb 2014 and Apr 2016 were enrolled in this prospective trial. Concentrations of total, corrected, and ionized calcium and their relationship with APACHE score and disease severity were noted during the study. RESULTS: There was a strong and inverse correlation between disease severity and ionized calcium concentration (P < 0.001, r = -0.697). There was a medium and significant inverse correlation between disease severity and total calcium concentration (P < 0.001, r = -0.368). Weak and direct significant correlation was observed between disease severity and corrected calcium concentration (P 0.02, r = 0.232). CONCLUSIONS: A significant correlation was found between total and ionized calcium, but there was not any significant correlation between corrected and ionized calcium. Hypocalcemia is a predictor of disease severity and mortality. We recommend measuring ionized calcium concentration for patients admitted to ICU.

Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin.

OBJECTIVES: Sepsis can result in severe organ injury by provoking inflammatory cascades and oxidative stress. Several studies are currently underway to find a drug with anti-inflammatory effects to prevent mortality and morbidity during sepsis. The present study was undertaken to assess the effects of metformin on oxidative stress and antioxidant status in sepsis induced by the Cecal Ligation and Puncture (CLP) method. MATERIALS AND METHODS: Male Wistar rats were divided into 4 groups (n=10): sham, CLP, and 50 and 100 mg/kg metformin-treated CLP groups. After 12 hr, blood samples were collected and lung tissue was removed for histopathological study to detect tissue damage and degree of inflammation based on neutrophil infiltration and assay of the oxidative stress biomarkers superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase (GPx), and plasminogen activator inhibitor-1 (PAI-1). RESULTS: The MPO activity and MDA level were decreased in the metformin-treated groups (P<0.05). Moreover, the groups receiving metformin showed lower inflammation scores than the CLP group (P<0.05). No significant differences in SOD, GPx, or PAI in the different groups were observed. The TAC level was reduced in the CLP group compared to the sham group (P<0.05), and interestingly, this value was reduced even further in the metformin-treated groups (P<0.05 compared with the CLP group). CONCLUSION: It was concluded that metformin protects lung tissue against sepsis-induced oxidative damage, and this protective effect may be more related to its anti-inflammatory and reduced neutrophil accumulation and less to its anti-oxidative properties.

Evaluation of Clinical Pharmacy Services in the Intensive Care Unit of a Tertiary University Hospital in the Northwest of Iran.

OBJECTIVE: Current literature indicates that the presence of clinical pharmacists in hospitals results in improved patient care, rational drug therapy, and treatment costs. This study assessed the clinical pharmacy services in the intensive care unit (ICU) of a tertiary hospital at Tabriz University of Medical Sciences, Iran. METHODS: During a 9-month cross-sectional study (2014-2015), the clinical pharmacy interventions in 27 sessions and educational activities for patients and health-care professionals were randomly assessed based on the Australian guideline and standard of practice for clinical pharmacy. The interventions of clinical pharmacist were evaluated in terms of their clinical importance. FINDINGS: In this study, a total of 832 interventions on 242 patients were performed by the clinical pharmacist, and approximately 93.6% of the interventions were approved by the attending physician. Most interventions concerned adding a new medication to a drug regimen or switching to a needed new medication. Each patient received an average of three interventions. The clinical pharmacist provided drug information to employees and medical staff in 108 of the total 832 interventions (13%). Medical residents who were surveyed indicated that the quality of education, research, and patient care was improved by the attendance of a clinical pharmacist. CONCLUSION: The results of this study show that the collaboration of a clinical pharmacist with the medical staff of an ICU can improve pharmacotherapy approach and increase the quality of education.

Calculating reading ease score of patient package inserts in Iran.

BACKGROUND: The patient package inserts (PPIs), which contain the necessary information about medications intended for patients, need to be expressed in a clear language comprehensible to everyone. OBJECTIVE: This study aimed to evaluate the readability and understandability of the drug package inserts for the inexpert people. METHODS: The readability of the 158 PPIs of the 33 drugs, registered and manufactured in Iran, was calculated. The main criterion for selecting PPIs to include in this study was of those top-selling drugs during the year 2015 according to the Social Security Organization in Iran. The PPIs were collected from the pharmacies of the three major cities, namely, Tabriz, Ardabil and Meshgin Shahr. Then, using the Flesch-Dayani readability (FDR) tool adjusted for the Persian language, the average number of the words and syllables was counted to calculate and grade the readability score of the selected PPIs. RESULTS: This study showed that the average FDR readability score for all the 33 drugs is 52.52, which are graded 10th-11th. Of the PPIs, 70.89% were difficult to read, and on average, the readability of the PPIs was five times difficult than the standard ones. Only 13.92% PPIs were suitable for the 5th-7th grade, and 15.19% of the package inserts ranked in the 8th-9th reading grade. CONCLUSION: A considerable number of the PPIs in Iran have low readability level and were not suitable for the inexpert readers. Since the treatment cost is very high, people tend to use medications arbitrarily or simply use old prescriptions. This study suggests the necessity of a major improvement in the readability level of the PPIs in order to ensure the usefulness of the PPIs to the majority of the consumers.

A pilot trial of l-carnitine in patients with traumatic brain injury: Effects on biomarkers of injury.

OBJECTIVE: To investigate the effects of l-Carnitine on neuron specific enolase (NSE) as a marker of inflammation in patients with traumatic brain injury (TBI). METHODS: Forty patients with severe TBI were randomized into 2 groups. The (LCA-) group received standard treatment with placebo while the (LCA+) group received l-Carnitine 2g/day for one week. NSE was measured on days 1, 3 and 7 after the initiation of the study. Neurocognitive and neurobehavioral disorders were recorded on the first and third months. RESULTS: Neurocognitive function and NSE significantly improved within one week in both groups. Patient mortality was similar in LCA+ and LCA- groups (P value: 0.76). Brain edema was present in 7 patients in LCA+ group and 13 patients in LCA-group (P value: 0.044). While there was no difference in NSE levels between the two groups. Neurological function was preserved in the LCA+ group with an exception of attention deficit, which was frequent in the LCA+ group. CONCLUSION: We concluded that despite improvements in neurobehavioral function and the degree of cerebral edema, 7-days of treatment with l-Carnitine failed to reduce serum NSE levels or improve mortality rate at 90days in patients with TBI.

High-dose amikacin for achieving serum target levels in critically ill elderly patients.

INTRODUCTION: To achieve target concentrations, the application of higher-than-standard doses of amikacin is proposed for the treatment of sepsis due to an increase in volume of distribution and clearance, but little data are available on aminoglycoside administration in critically ill elderly patients. PATIENTS AND METHODS: Forty critically ill elderly patients (aged over 65 years) who required amikacin therapy due to severe documented, or suspected gram-negative infections, were randomly assigned to two treatment groups. Group A (20 patients) received 15 mg/kg amikacin and Group B (20 patients) received 25 mg/kg amikacin per day as a single daily dose. All the patients were monitored for renal damage by the daily monitoring of serum creatinine. The amikacin peak (Cmax) and trough (Cmin) serum concentrations were measured on Days 3 and 7 postadministration. RESULTS: Data from 18 patients in Group A and 15 patients in Group B were finally analyzed. On Day 3, the amikacin mean Cmax levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (P<0.001), and the Cmin levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (P=0.035). On Day 7, the Cmax levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (P=0.001), and the Cmin levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (P=0.002). In only six (40%) of the patients in the high-dose groups and none of the patients in the standard-dose group, amikacin Cmax reached the target levels (>64 µg/mL), whereas the amikacin mean Cmin levels in the high-dose group were above the threshold of toxicity (5 µg/mL). CONCLUSION: Our results suggest that the optimum dose of amikacin should be determined for elderly critically ill patients. It seems that higher-than-standard doses of amikacin with more extended intervals might be more appropriate than standard once-daily dosing in the elderly critically ill patients.