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.

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.

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.

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.

The Effect of Furosemide on the Level of Neutrophil Gelatinase-associated Lipocalin in Critically Hospitalized Patients with Acute Kidney Injury.

BACKGROUND AND AIMS: Oliguric acute kidney injury (AKI), commonly attributed to a more severe degree of renal injury, is associated with poorer prognosis than nonoliguric form. The aim of this study was to determine the effect of furosemide therapy on kidney function and on the level of neutrophil gelatinase-associated lipocalin (NGAL) in critically hospitalized patients in the Intensive Care Unit (ICU). MATERIALS AND METHODS: In this randomized controlled trial, 106 ICU patients with AKI were assigned into furosemide and control groups. In furosemide group, 40-80 mg of intravenous furosemide was administrated, followed by 1-5 mg/h furosemide infusion. In control group, patients received standard treatment. Serum and urinary NGAL were measured on the 1st, 3rd, and 7th days of the study. RESULTS: The results of this study indicated that during the study, serum blood urea nitrogen levels of patients increased in both groups; this, however, was significant only in the control group (P = 0.009). Both plasma and urine NGAL decreased significantly (P < 0.05) in both groups. The findings of 28-day mortality follow-up revealed that 20% and 28% of patients died in the furosemide and the control groups, respectively. CONCLUSIONS: NGAL was not found to reflect any positive or negative effects of Furosemide in patients with AKI.

Relationship between glycated hemoglobin, Intensive Care Unit admission blood sugar and glucose control with ICU mortality in critically ill patients.

BACKGROUND AND AIMS: The association between hyperglycemia and mortality is believed to be influenced by the presence of diabetes mellitus (DM). In this study, we evaluated the effect of preexisting hyperglycemia on the association between acute blood glucose management and mortality in critically ill patients. The primary objective of the study was the relationship between HbA1c and mortality in critically ill patients. Secondary objectives of the study were relationship between Intensive Care Unit (ICU) admission blood glucose and glucose control during ICU stay with mortality in critically ill patients. MATERIALS AND METHODS: Five hundred patients admitted to two ICUs were enrolled. Blood sugar and hemoglobin A1c (HbA1c) concentrations on ICU admission were measured. Age, sex, history of DM, comorbidities, Acute Physiology and Chronic Health Evaluation II score, sequential organ failure assessment score, hypoglycemic episodes, drug history, mortality, and development of acute kidney injury and liver failure were noted for all patients. RESULTS: Without considering the history of diabetes, nonsurvivors had significantly higher HbA1c values compared to survivors (7.25 ± 1.87 vs. 6.05 ± 1.22, respectively, P < 0.001). Blood glucose levels in ICU admission showed a significant correlation with risk of death (P < 0.006, confidence interval [CI]: 1.004-1.02, relative risk [RR]: 1.01). Logistic regression analysis revealed that HbA1c increased the risk of death; with each increase in HbA1c level, the risk of death doubled. However, this relationship was not statistically significant (P: 0.161, CI: 0.933-1.58, RR: 1.2). CONCLUSIONS: Acute hyperglycemia significantly affects mortality in the critically ill patients; this relation is also influenced by chronic hyperglycemia.

Validity of bedside blood glucose measurement in critically ill patients with intensive insulin therapy.

BACKGROUND AND AIMS: There have been variable results on the practice of tight glycemic control, and studies have demonstrated that point-of-care (POC) glucometers have variable accuracy. Glucometers must be accurate, and many variables can affect blood glucose levels. The purpose of this study was to determine the difference between blood glucose concentrations obtained from POC glucometers and laboratory results in critically ill patients with intensive insulin therapy. MATERIALS AND METHODS: This was a descriptive study which enrolled 300 critically ill patients. Four samples of arterial blood were collected and analyzed at the bedside with the POC glucometer and also in the central laboratory to obtain the blood glucose level. To define the effect of various factors on this relation, we noted the levels of hemoglobin (Hb), PaO2, body temperature, bilirubin, history of drug usage, and sepsis. RESULTS: There were not any significant differences between blood sugar levels using laboratory and glucometer methods of measurements. There was a good and significant correlation between glucose levels between two methods (r = 0.81, P < 0.001). Among evaluated factors (body temperature, bilirubin level, blood pressure, Hb level, PaO2, sepsis, and drugs) which added one by one in model, just drugs decreased the correlation more than others (r = 0.78). CONCLUSIONS: The results of POC glucometer differ from laboratory glucose concentrations, especially in critically ill patients with unstable hemodynamic status while receiving several drugs. This may raise the concern about using POC devices for tight glycemic control in critically ill patients. These results should be interpreted with caution because of the large variation of accuracy among different glucometer devices.

A pilot randomized trial of pentoxifylline for the reduction of periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

PURPOSE: Periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) has received great attention due to its significant association with mortality and morbidity. Accordingly, cardioprotection during PCI is one of the important therapeutic concerns. Regarding the potential cardiovascular benefits of pentoxifylline this study was performed to evaluate whether the pretreatment pentoxifylline could reduce PMI in patients who are undergoing elective PCI. METHODS: A randomized clinical trial on 85 patients undergoing elective PCI was performed. The intervention group (n = 41) received 1200 mg pentoxifylline in divided doses plus the standard treatment before PCI, while the control group (n = 44) received the standard treatment. For assessing myocardial damage during PCI, the levels of CK-MB and troponin-I were measured at baseline, 8, and 24 h after the procedure. Then, patients were followed up for a 1-month period regarding the major adverse cardiac effect. RESULTS: Comparing with the control group, no significant change of CK-MB at 8 (p = 0.315) and 24 h (p = 0.896) after PCI was documented in pentoxifylline group. Similarly, no significant change was found in troponin-I at 8 (p = 0.141) and 24 h (p = 0.256) after PCI. CONCLUSIONS: This study could not support the pretreatment with pentoxifylline in the prevention of PMI in patients undergoing elective PCI. However, the trend was toward the potential benefit of pentoxifylline.

Effect of a multispecies probiotic on inflammatory markers in critically ill patients: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Impairment of intestinal barrier function and increased translocation of bacteria to the systemic blood flow contribute to the emergence of sepsis. Probiotics might be of beneficial effects on critically ill-patients, modulating intestinal barrier function and reducing inflammation. The aim of this trial was to determine the effect of probiotics on inflammatory markers in critically ill-patients in Intensive Care Unit (ICU). MATERIALS AND METHODS: This trial was conducted on 40 critically ill-patients admitted to the ICU. Patients were randomly assigned to receive placebo or probiotic containing Lactobacillus, Bifidobacterium and Streptococcus thermophilus (VSL#3) for 7 days. Acute Physiology and Chronic Health Evaluation (APACHE II) score Sequential Organ Failure Assessment (SOFA) and systemic concentrations of interleukin-6 (IL-6), procalcitonin (PCT) and protein C were measured before initiation of the study and on days 4 and 7. RESULTS: A significant difference in IL-6 (P = 0.003), PCT (P = 0.014) and protein C (P < 0.001) levels, and also APACHE II and SOFA scores (P < 0.001) was seen over the treatment period between two groups. Moreover, there was a significant decrease in serum IL-6 levels (from 211.85 ± 112.76 to 71.80 ± 28.41) (P < 0.001) and PCT levels (from 1.67 ± 1.27 to 0.47 ± 0.41) (P < 0.001) and a significant increase in serum protein C levels (from 7.47 ± 3.61 to 12.87 ± 3.63) (P < 0.001) in probiotic group during the study. CONCLUSION: Probiotics could reduce inflammation in critically ill-patients and might be considered as an adjunctive therapy in the treatment of critically ill-patients.

Pro-inflammatory cytokine profile of critically ill septic patients following therapeutic plasma exchange.

UNLABELLED: Severe sepsis involves a generalized inflammatory response, mediated by a number of various cytokines and factors. Plasma exchange (PE) has been proposed as a therapeutic approach to improve survival of patients with severe sepsis and septic shock. The theory is that removing harmful excessive endogenous inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe sepsis, twelve patients received PE plus conventional sepsis treatment. Interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α were assayed before and after each session of PE. RESULTS: There were no significant changes in cytokine plasma levels after each PE session compared to pre-procedure levels. Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before the 2nd and 3rd PE sessions were lower than baseline levels (p=0.011 and p=0.012, respectively). All patients tolerated PE therapy well without any adverse effects or homodynamic instability. The results of this study showed that PE does not have a direct and rapid effect on plasma level of TNF-α, IL-1ß and IL-6.

Effect of a probiotic preparation (VSL#3) in critically ill patients: A randomized, double-blind, placebo-controlled trial (Pilot Study).

UNLABELLED: Objective : Reactive oxygen species (ROS) are a major contributing factor in diseases pathophysiology in critically ill patients. Oxidative stress usually occurs in critical illnesses, specifically during sepsis, and organ dysfunction. The anti-oxidative properties of probiotics may serve as a defense in intestine and overcome various oxidative stresses. The aim of this trial was to determine the effect of probiotics on inflammation, antioxidant capacity and lipid peroxidation in critically ill patients. Methodology : Forty patients admitted to the intensive care unit were enrolled in this double-blind, randomized controlled trial. They were randomized to receive placebo or probiotic for 7 days. Serum levels of Total Antioxidant Capacity (TAC), Malodialdehyde (MDA), C-Reactive Protein (CRP) and Acute Physiology and Chronic Health Evaluation (APACHE II) score were measured before initiation of the study and on the 7(th) day. RESULTS: There was a significant difference in CRP levels and APACHE II score between two groups at the end of the study (P= 0.003 and 0.001, respectively). There was not a significant difference in levels of TAC and MDA between two groups. CONCLUSIONS: Administration of probiotics to critically ill patients caused reduction in inflammation and improvement of clinical outcome. However, there were not significant changes in markers of oxidative stress.

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.

The efficacy of magnesium sulfate loading on microalbuminuria following SIRS: One step forward in dosing.

BACKGROUNDS: Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebo control group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial. METHODS: 45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α), total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were also determined. RESULTS: Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024). Patient's mortality (28 day) was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing any complications. CONCLUSION: No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to prevent microalbuminuria.

Comparison of hypertonic saline versus normal saline on cytokine profile during CABG.

BACKGROUND AND THE PURPOSE OF THE STUDY: Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. METHODS: The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. RESULTS AND MAJOR CONCLUSION: Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation.

Positive effect of septimeb™ on mortality rate in severe sepsis: a novel non antibiotic strategy.

BACKGROUND: Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis. METHODS: In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2. RESULTS: A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn't change significantly between the two groups (P>0.05). CONCLUSION: Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.

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.

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.

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.

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.

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.