Tyrosine kinase inhibitors-associated pyoderma gangrenosum, a systematic review of published case reports.

Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the reported evidence of pyoderma gangrenosum associated with the use of these drugs. A systematic electronic literature search of PubMed and Embase was conducted. In these databases, search terms describing pyoderma gangrenosum were combined with TKIs. Fifteen case reports (eight cases associated with sunitinib, two with imatinib, two with ibrutinib, one with gefitinib, one with pazopanib, and one with dabrafenib and trametinib) were identified over the 14 years. The average Naranjo score of these cases is 6.6, which indicates a probable adverse drug reaction. Pyoderma gangrenosum is a probable and reversible drug reaction associated with some TKIs. Detailed medical history can help to prompt diagnosis of drug-induced pyoderma gangrenosum. Clinicians should be aware of TKI-associated pyoderma gangrenosum when caring for the skin of oncologic patients undergoing therapy with kinase inhibitors.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Evaluation of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 as biomarkers of renal function in cancer patients treated with cisplatin.

INTRODUCTION: Cisplatin-associated acute kidney injury (AKI) is the major limitation to the use of cisplatin-based chemotherapy regimens. Serum creatinine as a traditional marker did not increase in a timely enough fashion in AKI patients. Therefore, recently, the novel markers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were considered for early detection of AKI. The aim of this study was to compare the sensitivity and specificity of urinary NGAL and KIM-1 with serum creatinine in cisplatin related AKI. METHODS: Patients ≥18 years with solid tumors who received cisplatin-based chemotherapy were included. Urine samples were collected 0, 6 and 24 h after cisplatin infusion and the urinary NGAL, KIM-1, and creatinine concentrations were evaluated. NGAL and KIM-1 concentrations were adjusted based on urine creatinine to eliminate hydration effects. Serum creatinine levels were assessed at the base and 72 h after cisplatin administration. RESULTS: Seven out of the 35 recruited patients (20%) suffered from AKI defined by Acute Kidney Injury Network criteria. In AKI patients, the ratio of urinary KIM-1-creatinine at 24 h compared to baseline (24 h/baseline) and NGAL-creatinine 24 h/baseline were significantly higher than those of non-AKI group (p = 0.037 and 0.047 respectively). The area under the receiver-operating characteristic curve for KIM-1-creatinine 24 h/baseline and NGAL-creatinine 24 h/baseline were 0.78 (0.59-0.96, p = 0.032) and 0.77 (0.57-0.97, p = 0.036) respectively. CONCLUSIONS: Our findings showed that the changes in urinary NGAL-creatinine and KIM-1-creatinine ratios, 24 h after cisplatin administration can be utilized to predict AKI in cisplatin recipients.

Appropriateness of using granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis of febrile neutropenia in solid tumors.

INTRODUCTION: Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. METHOD: This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. RESULT: Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). CONCLUSION: Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.

Successful desensitization of a patient with cetuximab hypersensitivity: A case report.

BACKGROUND: Severe hypersensitivity reaction is a dangerous adverse drug reaction in patients receiving cetuximab. It requires drug discontinuation and medical management. CASE DESCRIPTION: A 48-year-old man, previously diagnosed with metastatic colorectal cancer, was admitted for therapy continuation. During the first infusion of cetuximab, the patient experienced acute signs of hypersensitivity reactions. The treatment team decided to administer cetuximab employing the desensitization protocol. CONCLUSIONS: This study reports a severe hypersensitivity reaction to cetuximab in an adult patient with colorectal cancer. This patient was successfully managed with a new safe and rapid desensitization protocol.

Effects of amniotic membrane extract and deferoxamine on angiogenesis in wound healing: an in vivo model.

OBJECTIVE: Angiogenesis, formation of new vessels from pre-existing vessels, is an essential part of wound healing. We aimed to compare amniotic membrane extract with deferoxamine in angiogenesis and to assess any synergistic effect. METHOD: We examined four groups of rats (five per group): control, deferoxamine, amniotic membrane extract, and deferocxamine and amniotic membrane extract in combination. A distal-based skin flap was created. Deferoxamine (100mg/kg), amniotic membrane extract (0.1mg/ml), and the combination of both were injected subcutaneously every other day in 10 separate points (0.1 ml at each point) in the skin flap. On day 11, the animals were euthanised for histopathological evaluation. RESULTS: Results indicated that the amniotic membrane extract raised the angiogenic markers, particularly new vessel numbers (p<0.008) and CD31+ compared with controls (p <0.003), and deferoxamine increased new vessel numbers and Von Willebrand factor (vWF) significantly compared with controls (p<0.008). There was an increase in angiogenic factors in the combined group, however, this was not statistically significant difference was observed. There was no difference between amniotic membrane extract and deferoxamine. CONCLUSION: Amniotic membrane extract or deferoxamine could be used interchangeably in angiogenesis within wound healing due to their high safety and availability.

The efficacy of erythropoietin mouthwash in prevention of oral mucositis in patients undergoing autologous hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

Oral mucositis (OM) as a complication of high-dose chemotherapy is frequently occurred in hematopoietic stem cell transplantation (HSCT) settings. Erythropoietin (EPO) has anti-inflammatory, antioxidant and wound-healing properties and therefore could have an important role in the prevention of OM. We conducted a double-blind, randomized, placebo-controlled trial to evaluate the EPO mouthwash effect on OM incidence and severity in 80 patients with non-Hodgkin's lymphoma, Hodgkin disease (HD) or multiple myeloma, undergoing autologous hematopoietic stem cell transplantation. Patients received either EPO mouthwash (50 IU/ml, 15 ml four times a day) (n = 40) or placebo (n = 40) from the starting day of high-dose chemotherapy until day +14 after transplantation or until the day of discharge from the hospital, whichever occurred first. OM was evaluated daily for 21 days after transplantation or until resolution of OM according to World Health Organization oral toxicity scale. The incidence of OM (grades 1-4) in the EPO mouthwash group and control group was significantly different (27.5% vs 77.5%, p < 0.001). The mean ± SD of two other parameters of OM including maximum intensity OM score (0.60 ± 1.06 vs 1.67 ± 1.27) and average intensity OM score (0.47 ± 0.80 vs 1.28 ± 0.86) was significantly lower in the intervention group (p < 0.001). Moreover, the mean ± SD duration of OM was also significantly shorter among the EPO mouthwash recipients (1.92 ± 3.42 days vs 5.42 ± 3.86 days, P < 0.001). Also, the duration of neutropenic fever was significantly shorter in the intervention group (2.12 ± 2.42 days vs 3.95 ± 4.01 days, p = 0.016). It is concluded that EPO mouthwash can reduce the incidence and duration of OM. Copyright © 2015 John Wiley & Sons, Ltd.

Calcitriol for Oral Mucositis Prevention in Patients With Fanconi Anemia Undergoing Hematopoietic SCT: A Double-Blind, Randomized, Placebo-Controlled Trial.

Fanconi anemia is a rare inherited aplastic anemia, which is cured only by hematopoietic stem-cell transplantation (HSCT). One of the most debilitating complications of high-dose chemotherapy regimen before HSCT is oral mucositis (OM), which occurs frequently in this population. Vitamin D has identified immunoregulatory, anti-inflammatory, and antioxidant role. This study was designed to examine the efficacy of vitamin D in the prevention of OM in patients with Fanconi anemia undergoing allogenic HSCT. Twenty-eight patients were enrolled in the study. They received either calcitriol (0.025 µg) or placebo capsule once daily, from the first day of chemotherapy schedule for 14 consecutive days. Incidence of OM was assessed as the primary outcome. Moreover, the association of baseline vitamin D level with OM was evaluated. In this study, calcitriol did not change OM incidence (P = 1) and severity (P = 0.54) significantly; however, a significant association of baseline vitamin D level with OM complete resolution was found (P = 0.03; hazard ratio, 1.01; 95% confidence interval, 1.00-1.01). In conclusion, we did not find considerable benefits of calcitriol in the prevention of OM. However, further studies with bigger sample size and different calcitriol supplementation schedules are needed to confirm these findings.

Burden of nosocomial infections in intensive care units: Cost of antibiotics, the extra length of stay and mortality rate.

Background: Healthcare-associated infections (HAIs) in intensive care unit (ICU) patients significantly complicate the normal hospitalization process and affect patients' condition, length of hospitalization, mortality, and treatment cost. In this study, we aimed to determine the prevalence and economic burden of HAIs. Methods: The study involved all patients with a confirmed HAIs (based on CDC/NHSN case-definitions); in the general ICU of a tertiary university hospital in Tehran, from April 2020 to March 2021. The patients' information, including length of hospitalization, outcome, type and cost of prescribed antibiotics, were recorded. Results: During the study period, 119 HAIs were found in 1395 (43% F / 57% M) patients. The prevalence of nosocomial infections was 8.53%. The mean duration of hospitalization in all ICU patients was 4.7 ± 3.1 days, and 31.85 ± 18.96 days in patients with HAIs. The most common organisms involved in HAIs are Acinetobacter baumannii (54.6%), Klebsiella pneumoniae (30.3%), E. coli (15.1%), and Enterococcus spp. (12%). Incidence density of ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI), and catheter-associated urinary tract infection (CA-UTI) per 1000 device-days were 36.08, 17.57, and 8.86, respectively. The total cost of antibiotics for HAIs was € 105,407. Among these, the highest consumption costs were for carbapenems, followed by colistin and caspofungin. Conclusion: This study showed the high burden of nosocomial infections in ICUs. Strategies for more strict infection prevention and control are necessary to reduce this burden.

Upfront DPYD Genotype-Guided Treatment for Fluoropyrimidine-Based Chemotherapy in Advanced and Metastatic Colorectal Cancer: A Cost-Effectiveness Analysis.

OBJECTIVES: Fluoropyrimidines are the most widely used chemotherapy drugs for advanced and metastatic colorectal cancer (CRC). Individuals with certain DPYD gene variants are exposed to an increased risk of severe fluoropyrimidine-related toxicities. This study aimed to evaluate the cost-effectiveness of preemptive DPYD genotyping to guide fluoropyrimidine therapy in patients with advanced or metastatic CRC. METHODS: Overall survival of DPYD wild-type patients who received a standard dose and variant carriers treated with a reduced dose were analyzed by parametric survival models. A decision tree and a partitioned survival analysis model with a lifetime horizon were designed, taking the Iranian healthcare perspective. Input parameters were extracted from the literature or expert opinion. To address parameter uncertainty, scenario and sensitivity analyses were also performed. RESULTS: Compared with no screening, the genotype-guided treatment strategy was cost-saving ($41.7). Nevertheless, due to a possible reduction in the survival of patients receiving reduced-dose regimens, it was associated with fewer quality-adjusted life-years (9.45 vs 9.28). In sensitivity analyses, the prevalence of DPYD variants had the most significant impact on the incremental cost-effectiveness ratio. The genotyping strategy would remain cost-saving, as long as the genotyping cost is < $49 per test. In a scenario in which we assumed equal efficacy for the 2 strategies, genotyping was the dominant strategy, associated with less costs (∼$1) and more quality-adjusted life-years (0.1292). CONCLUSIONS: DPYD genotyping to guide fluoropyrimidine treatment in patients with advanced or metastatic CRC is cost-saving from the perspective of the Iranian health system.

Changes in gram negative microorganisms' resistance pattern during 4 years period in a referral teaching hospital; a surveillance study.

BACKGROUND AND PURPOSE: Surveillance studies evaluating antimicrobial susceptibilities are of great value in preventing the spread of resistant pathogens by elucidating the trend of resistance in commonly used antibiotics and as a consequence providing information for prescribing the most appropriate agent. This study is a longitudinal antimicrobial resistance surveillance study designed to evaluate the trend in antimicrobial resistance to gram negative microorganisms from 2007 to 2010. METHOD: During a four-year period (2007-2010) isolates derived from all patients admitted to infectious diseases ward of Imam Khomeini Hospital, the major referral center for infectious disease in Iran with the highest admission rates, were evaluated. Based on disk diffusion method and zone of inhibition size, the microorganism was regarded as to be sensitive, resistant or has intermediate susceptibility to the antimicrobial agents. RESULTS: The widest spread Gram-negative microorganism in all of isolates taken together in our study was E.coli (30%) followed by Stenotrophomonas maltophilia in 28.6% and Enterobacter spp. in 11.9%, respectively. The susceptibility to amikacin, imipenem, piperacillin/tazobactam, and nitrofurantoin was equal or above 50% for all microorganisms over four years. However, the susceptibility to ampicillin, ampicillin/sulbactam, cefotaxim, and ceftriaxone was less than 50% in derived isolates during the study period. CONCLUSION: In conclusion, the finding of the present study revealed that resistance rate to common antimicrobial agents in Iran is growing and isolates were susceptible mostly to broad-spectrum antibiotics including imipenem and piperacillin/tazobactam.

Assessment of Antibiotic Dispensing Practice in Community Pharmacies of Tehran, for 2 Common Infectious Symptoms, Using Simulated Patient Method.

Resistance to antibiotics is a worldwide concern and community pharmacies can play a strategic role in controlling this issue through rationalizing antibiotic consumption. Considering that dispensing any type of antibiotics without a prescription is prohibited according to Iran's regulations, this study was conducted to quantify the rate of antibiotic dispensing without a prescription by pharmacists in Tehran, Iran. A descriptive cross-sectional study was conducted from September 2016 through May 2017. Two scenarios of common infectious symptoms including sore throat and dysuria were simulated by pharmacy student in three different regions of Tehran. Each scenario was performed in three levels of demand including requesting for any medicine, asking for a stronger medicine, and direct request for an antibiotic. A total of 388 pharmacy visits were acceptable including 195 and 193 pharmacies for dysuria and sore throat, respectively. Antibiotics were provided in 39.9% of dysuria (67.5% in the first level of demand) and in 52.3% of sore throat (49% in the first level of demand) simulations. The time devoted by the pharmacists to each case was less than 60 second in more than 90% of the cases. The completion of the course of antibiotic therapy was emphasized by pharmacists in only 18% of cases in both scenarios. Our findings revealed that antibiotic dispensing without a prescription is a routine practice in community pharmacies in Tehran, Iran. Unfortunately, patient assessment and evaluation of the symptoms are not performed properly by pharmacists as well.

Effect of Selenium on Incidence and Severity of Mucositis during Radiotherapy in Patients with Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) is the most frequent side effect of radiation. Selenium deficiency leads to increased levels of free oxygen radicals and the selenium level tends to fall during radiotherapy. Hence, in this double-blind randomised controlled clinical trial, the effect of selenium was assessed in patients receiving radiation. MATERIALS AND METHODS: Patients with head and neck cancer who were candidates to receive radiation were instructed to use selenium 200 mcg tablets twice daily. The grade of OM was evaluated by the World Health Organization (WHO) grading system on a weekly basis. The selenium level was measured at baseline and at the end of the radiation. RESULTS: Seventy-one patients with head and neck cancer (37 in the selenium group, 34 in the placebo group) were enrolled in the study. The cumulative incidence of OM (grade 1-4) was 97.3% in the selenium and 100% in placebo group (p value: 0.79), and difference in the mean serum selenium level at the end of radiation was not statistically significant between the two groups (p value 0.24) Conclusion: Selenium supplementation does not appear to affect the selenium level as well as the severity and duration of OM. It is supposed that higher doses may be effective in the prevention of RT-mucositis. This trial was registered in the Iranian Registry of Clinical Trials accessible at www.irct.ir (ID No. IRCT2014072718612N1).

Evaluation of Venous Thromboembolic Event Prophylaxis in Hospitalized Cancer Patients: A Single-Centered Retrospective Study.

OBJECTIVE: Venous thromboembolic events (VTEs) are one of the main causes of death in cancer patients. About one-third of newly diagnosed VTEs are later proved to be associated with cancers. Attempts have been made to prevent these events and reduce substantial burden on patient health. Previous studies have revealed underutilization of thromboprophylaxis in cancer patients. With respect to the high rate of enoxaparin prescription in our institute, irrational utilization of prophylactic measures was anticipated. This study aimed to evaluate the appropriateness of thromboprophylaxis in hospitalized cancer patients. METHODS: Medical records of 199 cancer patients hospitalized in two oncology wards of a tertiary care teaching hospital were investigated retrospectively. Data extraction was performed by two clinical pharmacists. Appropriateness of thromboprophylaxis was determined using a local protocol prepared based on international guidelines. FINDINGS: Forty-seven out of 199 prescriptions (23.5%) were appropriate according to the local protocol. About 76% (149/199) of patients did not have any acute medical illness or risk factors for thromboembolism and were admitted only to receive short-course chemotherapy. Enoxaparin was the drug used for 197 patients and unfractionated heparin was used for only 2 patients. Dose adjustment was not performed in three patients who needed dose modification with respect to renal impairment or obesity. CONCLUSION: This study has found that the frequency of thromboprophylaxis was considerably high in the study population. In the absence of an acute medical illness or other risk factors, hospitalization per se does not justify the administration of pharmacologic agents for thromboembolism prophylaxis. Implementation of local protocols prepared based on international guidelines seems necessary to rationalize thromboprophylaxis.

Is Albumin-based Resuscitation in Severe Sepsis and Septic Shock Justifiable? An Evidence from a Cost-effectiveness Evaluation.

BACKGROUND: Fluid and antimicrobial therapy are the essential parts of sepsis management. The type of fluid to resuscitate with is an unsettled issue in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate the cost-effectiveness of albumin-based resuscitation over crystalloids. METHODS: A cost-effectiveness analysis was conducted by extracting data from a database of Sina Hospital, Islamic Republic of Iran. A decision tree was constructed by using Tree Age Pro 2011. The patients were grouped based on the types of fluids used for resuscitation into crystalloid alone or crystalloid + albumin groups at the initial decision node. The patients were followed from the onset of severe sepsis and septic shock upto 28 days. The healthcare payers' perspective was considered in constructing the model. The cost was measured in US dollars and the effectiveness was measured by life years gained. RESULTS: The addition of albumin during resuscitation of patients with severe sepsis and septic shock has an effectiveness gain of 0.09 life years and cost increment of 495.00 USD. The estimated ICER for this analysis was 5500.00 USD per life year gained. The probability that albumin is cost-effective at one GDP per capita is 49.5%. CONCLUSION: Albumin-based resuscitation is not cost-effective in Iran when a GDP per capita was considered for a life year gain. The cost-effectiveness was insensitive to the cost of standard care. We recomend the caustious use albumin as per the Surviving Sepsis Campaign guideline.

Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial.

BACKGROUND: Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited. OBJECTIVES: The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma following autologous peripheral blood HSCT were assessed. METHODS: Eighty patients (age: 18-68 years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25 µg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated. RESULTS: Median time to ANC engraftment (≥0.5 × 103/µl: 10.0 vs. 11.0 days; P = 0.98) and PC engraftment (≥20.0 × 103/µl: both 14.0 days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/µl: 13.0 vs. 20.0 days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/µl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/µl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29 months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72). CONCLUSION: Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT. Graphical abstract Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.

A Cost-effectiveness Analysis of Albumin in Septic Shock: A Patient-level Data Analysis.

PURPOSE: Albumin-based fluid therapy in septic shock is a matter of debate and criticism. The aim of this study was to assess the cost-effectiveness of albumin therapy in patients with septic shock. METHODS: A retrospective cohort study was conducted in Imam Khomeini, Sina, and Shariati hospitals on patients with septic shock admitted to intensive care units from March 31, 2016 to September 22, 2017. Data sources were the health information system database and patient medical records. The patients with potential septic shock were identified based on norepinephrine use. Septic shock was confirmed after medical record review based on systemic inflammatory response syndrome criteria, antibiotic use, and fluid therapy. Patients who received albumin in the fluid therapy were compared with patients treated without albumin. The 28-day mortality, life-year gain, and cost-effectiveness were evaluated. FINDINGS: The addition of albumin had no significant increase in life-year gain (mean difference = 0.67; 95% CI, -2.25 to 3.58). However, the addition of albumin increased the total cost of treatment by US $3846.07 (95% CI, US $2093.46-US $5598.98). The incremental cost-effectiveness ratio calculated based on the mean life-years gained was US$5740.40 per a life-year gained. The net monetary benefit was negative (-355.4; 95% CI, -15,387.61 to 14,676.81), and the probability that the addition of albumin will be cost-effective at a gross domestic product per capita was 40.0%. IMPLICATIONS: Albumin-based fluid therapy does not improve the 28-day mortality of patients with septic shock. The addition of albumin in the fluid therapy of patients with septic shock was not cost-effective. Both the observational and retrospective nature of the study was expected to introduce bias. We recommend a cost-effectiveness analysis combined with clinical trials to settle the debate once and for all.

Efficacy of a telephone-based intervention among patients with type-2 diabetes; a randomized controlled trial in pharmacy practice.

Background Pharmacists' interventions to improve outcomes of diabetes management have been promising. However, evidence on using telephone-based interventions in pharmacy practice are limited, particularly in developing countries. Objective To evaluate the efficacy of a telephone-based intervention to improve care and clinical outcomes in type-2 diabetes. Setting A referral community pharmacy and drug information center. Method We conducted a two-armed randomized controlled trial on 100 patients with type-2 diabetes. The intervention consisted of 16 telephone calls in 3 month by a trained pharmacist working in an academic drug information center, while the control group received usual care. Before random allocation, patients attended a live education session delivered by pharmacists to learn the basics of diabetes care and to confirm the eligibility criteria. Assessments were performed at baseline, month-3 (after intervention), and month-9 (follow-up). Main outcome measure Hemoglobin A1c (HbA1c). Results Eighty four patient completed the trial. Baseline variables were comparable between the two groups and the baseline value of hemoglobin A1c was 8.00 ± 1.44 in the study population. HbA1c was significantly improved in both groups at month-3 (6.97 ± 1.41 vs. 7.09 ± 1.78) and remained steady at month-9 (6.96 ± 1.44 vs. 7.26 ± 1.85). Lipid profile showed small improvements in the intervention group but was not significant. The adherence score and self-care score improvement was significantly higher in the intervention group at month-3 and were maintained at month-9. Conclusion Medication adherence and self-care significantly improved in the telephone-based intervention group. However, the improvement of clinical outcomes might have been diluted due to the live diabetes education session.

Impact of Protocol Implementation on Rationalization of Albumin Use in a Tertiary Care Teaching Hospital in Tehran, Iran.

OBJECTIVE: With respect to the high cost and limited availability of albumin, its use must be restricted to indications strongly supported by solid scientific evidence. It was anticipated that with the implementation of the National Health Reform Plan (NHRP), the consumption of albumin would increase as the result of decreasing patients' out-of-pocket costs. This study aimed to evaluate the efficacy of protocol implementation on the rationalization of albumin use in surgery wards of Cancer Institute of Imam Khomeini Hospital Complex, Tehran, Iran. METHODS: This pre-post interventional study was conducted in 32-month phases from January to November 2014 in an Iranian University hospital. The first phase was before the implementation of NHRP, the second phase was after NHRP, and the last one was after the intervention. The first and second phases were conducted retrospectively. Data extraction was performed by a hospital pharmacist. During the third phase, the physicians were mandated to adhere to a local albumin protocol which had been prepared by clinical pharmacy service and approved by drug and therapeutic committee. Appropriateness of prescriptions regarding indication, dose, and duration based on local guideline was compared among groups. FINDINGS: Although hospital bed-days of care remained consistent among phases, albumin was prescribed for 40, 45, and 8 patients during first, second, and third phases, respectively. This shows about 80% reduction of drug prescriptions in the last phase. The mean duration/dose of albumin in inappropriate indications reduced significantly from 11.3 ± 8.2 days/24.7 ± 21.2 vials in the second phase to 2.6 ± 1.7 days/5.6 ± 3.5 vials in the third phase, respectively (P = 0.001 and P = 0.003). CONCLUSION: Interactive collaboration through guideline implementation seems effective in rationalizing the use of high-cost medications such as albumin.

Vancomycin-Induced Thrombocytopenia: A Narrative Review.

Thrombocytopenia has been reported as an adverse reaction of numerous drugs. Vancomycin is often overlooked as a culprit but has been associated with several cases of thrombocytopenia that were not well described in the literature. A literature search was conducted to find reports of thrombocytopenia induced by vancomycin. Biomedical databases including 'PubMed', 'Scopus', and 'Web of Science' were searched using terms 'vancomycin', 'platelet', 'pancytopenia', 'thrombocytopenia', and 'bleeding'. English language articles published before July 2015 were included. Thirty-nine papers including 29 case reports (30 cases), five observational studies, two clinical trials, two letters, and one case series remained for final analysis. The main route of administration was intravenous infusion. This adverse reaction seems to be duration dependent with the mean time to platelet nadir count of 8 days in reported cases. The interval may be significantly shorter in re-exposure to the drug. Platelet nadir counts ranged from 2000 to 100,000/mL in patients who experienced bleeding. Vancomycin-specific antibodies were detected in 13 of 17 patients who were tested in the case reports. Based on the Naranjo Adverse Drug Reaction Probability Scale, reaction was 'definite', 'probable', and 'possible' in 1, 15, and 14 patients, respectively. Among 30 cases, vancomycin was discontinued in 29 patients and platelets returned to normal counts within 5-6 days in 17 of them; in one patient, vancomycin was not discontinued, but platelet count recovered 11 days after the nadir time. Transfusion might be recommended if severe thrombocytopenia and bleeding occurs. Intravenous immunoglobulins, corticosteroids, rituximab, and plasma exchange should be reserved for patients with resistant thrombocytopenia and severe bleeding as mentioned in a number of reports.