Protective effects of silymarin on preventing vancomycin nephrotoxicity in infectious patients: a randomized, double-blinded, placebo-controlled, pilot clinical trial.

Nephrotoxicity is one of the most common complications of vancomycin use in clinical practice. Silymarin has potential to be a renoprotective agent for nephrotoxic drugs due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this clinical study is evaluating the potential effects of silymarin on preventing vancomycin nephrotoxicity. A multicenter, randomized, double-blinded, placebo-controlled, clinical trial was conducted on patients with the indication of systemic vancomycin for at least 7 days. Patients were screened daily and those who met the inclusion criteria were selected and randomly assigned into either silymarin or placebo groups. Accordingly, 140 mg silymarin tablet (Livergol®) or placebo was given orally three times daily. Silymarin or placebo were provided in conjunction with vancomycin for at least 7 days. If vancomycin therapy was extended beyond 7 days, the administration of silymarin or placebo was continued until the end of vancomycin treatment. Malondialdehyde, glutathione, and total antioxidant capacity were measured in the serum on days 0 and 7. A trough level of vancomycin was assessed 30 min before the fifth dose of vancomycin. Acute kidney injury (AKI) was monitored in each patient daily during the course of vancomycin treatment. The causality assessment of all identified cases of vancomycin associated AKI was performed by the Naranjo scale. The primary endpoint was vancomycin nephrotoxicity. It was defined based on the KDIGO 2012 criteria for AKI as either an increase of 0.3 units or more in serum creatinine level during 48 h or 50% (1.5-fold) or more during 7 days compared to baseline values. During the study period, 34 patients in the silymarin group and 32 patients in the placebo group completed the clinical trial. Demographic, baseline clinical, and laboratory characteristics were comparable between placebo and silymarin groups. The number of patients with AKI on days 5, 6, 7, 11,12, 13, and 14 in the placebo group was significantly higher than that in the silymarin group (p-value < 0.05). The incidence of acute tubular injury on the day  5 and 7 of vancomycin treatment was significantly lower in the silymarin group (p-value = 0.005 and p-value = 0.032, respectively). Antioxidant indexes including serum total antioxidant capacity and glutathione significantly increased in the silymarin group (p-value < 0.001 for both indexes). In contrast, serum malondialdehyde as an end product of lipid peroxidation pathway significantly decreased in the silymarin group during 7 days (p-value < 0.001). The results of the present pilot, clinical trial suggested that silymarin co-administration may prevent vancomycin nephrotoxicity.

Thyroid diseases in children and adults with celiac disease: A cross-sectional study.

Background: There are few reports evaluating different factors, including the severity of duodenal histopathological findings and serological levels of celiac disease (CD), in increasing the probability of thyroid diseases (TD) in adults and children with CD, so, we designed this research. Methods: CD was defined as Marsh type 2 or higher in duodenal histopathology and serological levels of anti-transglutaminase antibodies (anti-tTG) equal to or greater than 18 IU/ml. To assess the likelihood of TD in CD patients, logistic regression analysis was employed. Results: 538 patients were included in this study. Of these, 354 (65.8%) were females and 184 (34.2%) were males. 370 (68.8%) patients were children. Overall, 57 (10.6%) patients had TD, of which 49 (9.1%) had hypothyroidism and 8 (1.5%) had hyperthyroidism. Adults had a significantly higher probability of developing TD than children (OR 1.9; 95% CI 1.1-3.4; P = 0.03). The odds of developing TD were also significantly higher in patients with family marriage in parents (OR 2.3; 95% CI 1.1-4.7; P = 0.03). Other variables such as gastrointestinal symptoms, anti-tTG levels, and severity of Marsh classification did not exhibit a substantial rise in the likelihood of TD development. Conclusion: The study findings indicated that the likelihood of developing TD in CD patients can be linked to advancing age and having family marriage in parents, while there was no significant association observed with anti-tTG levels, severity of histological damage, and gastrointestinal symptoms.

Extensive arm skin necrosis following administration of unfractionated heparin.

Unfractionated heparin (UH), a commonly used anticoagulant, can rarely cause skin necrosis following heparin-induced thrombocytopenia (HIT). A 38-year-old female, a case of chronic inflammatory demyelinating polyneuropathy (CIDP) admitted to the neurology ward, developed extensive skin necrosis following a change in UH dose at the exact site of UH injection. A sudden fall in the platelet count was observed within 48 h of increasing the UH dose. Necrosis of the outer layer of the skin along with clot formation and inflammation in the inner layers was detected after histopathological evaluation. UH was discontinued, and rivaroxaban was started for the patient as soon as the complication was detected. The patient was discharged in good condition after completing treatment for CIDP without any need for surgical removal of the necrotic tissue. Extensive skin necrosis, as a result of HIT, requires immediate discontinuation of UH and substitution of a nonheparin-based anticoagulation treatment.

Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19.

The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To prevent or treat primary SARS-CoV-2 infections, it is essential to target the virus port of entry in the respiratory tract and airway epithelium, which requires rapid and high-intensity inhibition or control of viral entry or replication. To achieve success in this field, inhalation therapy is the most attractive treatment approach due to efficacy/safety profiles. In this review article, pulmonary drug delivery as a unique treatment option in lung diseases will be briefly reviewed. Then, possible inhalation therapies for the treatment of symptoms of COVID-19 will be discussed and the results of clinical trials will be presented. By pulmonary delivery of the currently approved drugs for COVID-19, efficacy of the treatment would be improved along with reducing systemic side effects.

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

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

Case of possible encephalopathy following receiving the first dose of Iranian COVID-19Vaccine; COVIran Barakat.

We report a case of possible encephalopathy after receiving the first dose of Iran's COVIran Barekat vaccine. The patient had no history of neurological or mental illness. Clinical examinations and radiology reports were performed and differential diagnoses were analyzed by the treatment team. Finally, the possible association between vaccination and encephalopathy was concluded.

Psychiatric Adverse Drug Reactions and Potential Anti-COVID-19 Drug Interactions with Psychotropic Medications.

Coronavirus disease 2019 (COVID-19) management in patients with predisposing psychiatric disorders would be challenging due to potential drug-drug interactions (PDDIs) and precipitation of their disease severity. Furthermore, COVID-19 itself might precipitate or induce unpredicted psychiatry and neuropsychiatry complications in these patients. In this literature review study, the psychological impacts of COVID-19 and major psychiatric adverse drug reactions (ADRs) of COVID-19 treatment options have been discussed. A detailed Table has been provided to assess potential drug-drug interactions of COVID-19 treatment options with psychotropic medications to avoid unwanted major drug-drug interactions. Finally, potential mechanisms of these major drug-drug interactions and possible management of them have been summarized. The most common type of major PDDIs is pharmacokinetics. Hydroxychloroquine/chloroquine and lopinavir/ritonavir were the most involved anti-COVID-19 agents in these major PDDIs.

Impact of Serological and Histological Factors on Neurological Manifestations in Children and Adults with Celiac Disease.

PURPOSE: Celiac disease (CD) is a common autoimmune disease with extra-intestinal manifestations, including neurological disorders. There are few reports to assess various factors in increasing the chances of developing neurological disorders in CD, so we designed this study. METHODS: All patients with CD at any age who had been referred to the Celiac Clinic were evaluated for neurological problems. CD was defined as IgA anti-transglutaminase antibodies (anti-tTG) of 18 IU/mL or higher in serology and Marsh type I or more severe in histopathological evaluation. Logistic regression analysis was used to evaluate the impact of various independent variables on the neurological manifestations. RESULTS: A total of 540 patients enrolled in this study. A 360 (66.7%) of patients were children. A 64.8% and 35.2% were female and male, respectively. Overall, 34.1% of patients had neurological manifestation, including headache, neuropathy, epilepsy, and ataxia. The odds of developing neurological manifestations in children were significantly lower than in adults (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45-0.96; p=0.03) and in patients with gastrointestinal (GI) symptoms significantly higher than in the group without GI manifestations (OR, 1.77; 95% CI, 1.18-2.63; p=0.005). Other variables, including Marsh classification (OR, 0.44; 95% CI, 0.18-1.11; p=0.08) and anti-tTG levels (OR, 1.00; 95% CI, 0.999-1.001; p=0.59) did not significantly increase the chances of developing neurological disorders. CONCLUSION: Our study showed that increasing age and the presence of GI symptoms, but not serological and histological findings, could increase the chances of developing neurological diseases in CD patients.

A randomized double-blinded placebo-controlled clinical trial on protective effects of pentoxifylline on gentamicin nephrotoxicity in infectious patients.

BACKGROUND AND OBJECTIVE: Renal toxicity has limited gentamicin use in clinical practice. The aim of the present clinical trial was to assess the possible nephroprotective effects of pentoxifylline (PTX) against gentamicin nephrotoxicity. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted on patients who had the indication for systemic gentamicin for at least 7 days. Sixty people were selected and randomly assigned. For patients in the intervention and control groups, 400 mg PTX sustained release tablet and placebo were given orally three times daily, respectively. Demographic, clinical, laboratory, and therapeutic information of patients were recorded. malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in serum were measured on days 0 and 7. RESULTS: The incidence of nephrotoxicity in the placebo group was 19.6 times higher than that in the PTX group (OR = 19.6, 95%CI = 3.08-114.32; P value = 0.001). The mean ± SD time onset of ATN was 4.00 ± 2.32 and 5.58 ± 1.59 days in PTX and placebo recipients, respectively (P value < 0.001). No significant differences were observed for hypokalemia, hypomagnesemia, potassium and magnesium wasting between the two groups. The mean ± SD levels of serum MDA and TNF-α at day 7 were significantly lower in the PTX compared to those in the placebo group (P value < 0.001 for both indexes). CONCLUSION: The co-administration of 400 mg PTX orally three times daily along with gentamicin was both well-tolerated and effective in preventing the nephrotoxicity of gentamicin in patients with different infectious diseases.

Addition of carboplatin-gemcitabine as second-line neoadjuvant chemotherapy in non-responsive locally advanced breast cancer patients to standard neoadjuvant chemotherapy and evaluation of factors affecting response: a randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response. METHODS: In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. "Control" group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). "Intervention" group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery. RESULTS: In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the "intervention" group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident. CONCLUSION: Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the "intervention" group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity. TRIAL REGISTRATION: This trial was prospectively registered in IRCT.ir ( IRCT2017100136491N1 ). Date of registration: 19 November 2017.

A randomized controlled clinical trial comparing calcitriol versus cholecalciferol supplementation to reduce insulin resistance in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world with no definite treatment. Insulin resistance (IR) and low serum vitamin D are closely linked to NAFLD. Since there is no comparative study on the effect of calcitriol with cholecalciferol on NAFLD based on homeostasis model of insulin resistance (HOMA-IR) as an IR indicator, so we designed this research. METHODS: A double blind randomized clinical trial was conducted on patients with NAFLD with concomitant vitamin D deficiency/insufficiency at two referral tertiary teaching medical centers, from July 2017 to January 2019. Patients were randomly divided into two groups: calcitriol (1 mcg/day) and cholecalciferol (50,000 IU/week) for 8 weeks. Before and after the intervention, anthropometric and laboratory data were measured and HOMA-IR was calculated for each patient. RESULTS: 54 patients completed the trial. In total, calcitriol supplementation improved serum insulin levels as well as IR based on the HOMA-IR index, significantly compared to the cholecalciferol group. HOMA-IR decreased 1.8 times more in patients receiving calcitriol than in those receiving cholecalciferol, which was clinically meaningful. The observed changes were more pronounced in patients with higher baseline body mass index. Moreover, calcitriol was more associated with a significant decrease in liver enzymes and cholesterol levels comparing to cholecalciferol. CONCLUSION: Based on the findings of this study, the use of calcitriol supplementation significantly reduced HOMA-IR as an IR indicator in NAFLD patients, compared to cholecalciferol. To confirm this findings, further studies with larger sample sizes are recommended.

The Impact of an Antibiotic Stewardship Program on the Consumption of Specific Antimicrobials and Their Cost Burden: A Hospital-wide Intervention.

BACKGROUND: Inappropriate use of antimicrobials (AM) is a major concern worldwide that leads to the propagation of antimicrobial resistance (AMR). In addition to its clinical implications, AMR imposes an economic burden on communities, especially developing countries with more infectious diseases and less available resources. Antimicrobial stewardship programs (ASPs) have been found to be effective in reducing AMR. This study was designed to evaluate the effect of implementing an ASP in reducing AM consumption, its economic burden, and AMR as a consecutive result. MATERIALS AND METHODS: Consumption of caspofungin, amphotericin B, voriconazole, colistin, linezolid, vancomycin, and carbapenems was compared in a prospective cross-sectional study between two time periods introduced as pre- and post-ASP. Drug use density presented as anatomical therapeutic chemical (ATC)/defined daily doses (DDD) and normalized per 1000 bed days, cost savings, and AMR patterns were evaluated. RESULTS: A total of 9400 AM prescriptions were analyzed during a 2-year period. Consumption measured in DDD/1000 bed days dropped by 24.8, 25.0, 35.3, 47.0, 39.2, 10.5, and 23.2 percent for amphotericin B, caspofungin, colistin, voriconazole, meropenem, imipenem, and vancomycin, respectively. Linezolid consumption increased by 26.8% after implementing ASP. The expenditure of target AMs in the average value of USD decreased by 41.3% after the intervention compared to the time before using ASP (P-value=0.001). Implementing ASP also increased AM susceptibility of Pseudomonas aeruginosa, while the susceptibility of methicillin-resistant Staphylococcus aureus did not change significantly. CONCLUSION: The results of this study suggest that establishment of ASP can lead to a reduction in improper administration of AMs and their expenditure resulting in economic benefit and lowering AMR at hospitals with minimum resources. Clinical pharmacists' role was critical to the success of this ASP and was uniquely empowered at our center.

Association Between Metabolic Syndrome and Its Components with Severity of Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) and metabolic syndrome (MetS) are common clinical problems with serious complications and high cost of treatment. The relationship between MetS and severity of AP is unknown, and because there are very few published articles, further studies had been recommended. Therefore, we designed this study to estimate the association between MetS and its components with AP severity. PATIENTS AND METHODS: In this prospective analytical cross-sectional study, all AP patients who referred to two referral hospitals affiliated with Shiraz University of Medical Sciences between 2016 and 2019 were evaluated. The diagnosis of MetS syndrome as well as follow-up of patients for evaluation of severity and outcome of AP was performed in all enrolled patients. National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) was used for diagnosis of MetS. Bedside Index for Severity in Acute Pancreatitis (BISAP) and revised Atlanta classification (RAC) were used to estimate the severity of AP. Finally, the association between MetS syndrome and its components at different AP severities was compared. RESULTS: Of the 214 patients referred to our center, a total of 76 patients with AP were included in this study. Of the included patients, 40 (52.6%) were male and 36 (47.4%) were female. Frequency of patients in Mets and non-MetS groups was 34 (44.74%) and 42 (55.26%), respectively. The gender and mean age difference between Mets and non-MetS groups were not statistically significant. According to Mets groups, 25 (73.5%) and 9 (26.5%) AP patients with MetS had BISAP score of 0-2 and 3-5, respectively. BISAP score in MetS group was significantly higher than non-MetS group (P = 0.022). Overall, 20 (58.8%), 11 (32.4%), and 3 (8.8%) of AP patients with MetS had mild, moderately severe, and severe AP based on RAC, respectively. Severe RAC was significantly higher in the MetS group than in the non-MetS group (P = 0.029). The frequency of complications in MetS group was significantly higher than in non-MetS group (P= 0.008). The length of hospital stay was also significantly higher in the MetS group than in the non-MetS group (P = 0.001). Overall, three patients died, two of whom had MetS and all had severe RAC and BISAP 3-5. Waist circumference, fasting blood sugar, and triglyceride were significantly higher in the severe and moderately severe types of AP group than in the mild AP group, according to RAC. Although, mean of all components of MetS except HDL-cholesterol were higher in BISAP of 3-5 group than BISAP of 0-2 group, the difference was only significant in waist circumference. CONCLUSION: The present study showed that there was a significant association between the rate of MetS and its components including waist circumference, hyperglycemia and hypertriglyceridemia with increasing AP severity. This study showed that the incidence of more severe AP in patients with MetS is much higher than in patients without MetS. We recommend that the new studies with larger sample sizes are conducted with careful consideration of confounding factors to investigate the relationship between the severity of MetS and AP as well as the effect of MetS treatment on the nature of AP.

Knowledge, attitude, and practice of health care workers towards antibiotic resistance and antimicrobial stewardship programmes: A cross-sectional study.

RATIONALE AND AIMS: Antibiotic development was a major breakthrough in defeating infections; however, their vast use has led to antimicrobial resistance (AMR) causing mortality, morbidity, and financial burden worldwide. Considering the limited introduction of newer antimicrobials to overcome resistance patterns, sufficient knowledge of their use can help manage this issue. Antimicrobial stewardship programmes (ASPs) with the mainstay of education can be a good resolution. The aim of this study was to seek aspects in which knowledge regarding antibiotics is lacking at our institutions. MATERIALS AND METHODS: This cross-sectional study performed in Shiraz, South of Iran, was designed as a knowledge, attitude, and practice (KAP) study. A self-administered questionnaire consisting of 15 questions was designed and handed out to health care workers including infectious disease practitioners, surgeons, internal medicine specialists and residents, general practitioners, medical students, and microbiology lab technicians and PhD graduates. Difference in response to questions was evaluated between the practitioner and nonpractitioner groups. RESULTS: Completed questionnaires were collected (n = 126). According to the results, most participants (88.1%) agreed on establishment of local guidelines. Majority (94.4%) also believed that education regarding antibiotics can help reduce AMR. Good patient care was not believed to be impaired by limiting use of antibiotics (72.2%). A significant difference in the practitioner and nonpractitioner groups' practice score was observed. CONCLUSION: In our study, knowledge deficit was observed in some aspects of AMR. We can conclude that more practice and education are needed in ASP for the better performance in reducing resistant patterns.

Helicobacter pylori, Endoscopic, And Histologic Features Among Kidney Transplant Candidates In Southern Iran.

BACKGROUND: The risks of gastrointestinal disorders and cancer are higher in chronic kidney disease (CKD) patients than the general population. There are only a few published reports on the association of helicobacter pylori (H. pylori) infection, endoscopic findings, and histology in these patients. This study was designed to address these controversial topics among kidney transplant candidates as the first study in southern Iran. PATIENTS AND METHODS: In this cross-sectional study, patients undergoing renal transplantation in the largest center of southern Iran during 2016-2017 were evaluated for the frequency of H. pylori infection, endoscopic findings, and histology. Gastric endoscopic findings (normal, abnormal non-ulcerative, ulcerative) and histological findings of gastric biopsy (normal/non-significant, inflammation, premalignant lesions (PMLs), malignant lesions) were studied. RESULTS: In total, 293 patients underwent endoscopy for transplant work up. The mean age (SD) was 47.37 (13.14) years. The most common endoscopic finding was abnormal gastric lesions. Overall, 78.8% patients had abnormal gastric histologic findings, of which 6.1% had PMLs. There was no significant association between laboratory data of patients with H. pylori infection. Of these, 147 (50.2%) patients were positive and the others were H. Pylori negative. Positive H. pylori infection was significantly associated with gastric ulcerative lesions. Positive H. pylori infection was also strongly associated with inflammation (P<0.01), but not significantly associated with PMLs (P=0.99) in gastric histology. CONCLUSION: The present study showed that abnormal endoscopic and histologic findings as well as positive H. pylori infection were observed in a large number of kidney transplant candidates, so upper endoscopy with biopsy is an acceptable procedure for these patients. However, further studies are recommended to determine the relationship of H. pylori with abnormal endoscopic and histologic findings considering other confounding factors in kidney transplant candidates as well as the efficacy of H. pylori eradication therapy to improve these abnormal findings.

Economic Burden Of Inappropriate Empiric Antibiotic Therapy: A Report From Southern Iran.

INTRODUCTION: Widespread inappropriate antibiotic prescribing by healthcare professionals in the hospital setting is a great concern that may cause many undesirable consequences. Adherences to antibiotic guidelines have proven to be a simple and effective intervention to guide the choice of appropriate empiric antibiotic regimens and reduce the unnecessary variations in the practice among practitioners. The objective of this study was to evaluate the prescription patterns of empiric antibiotic therapy in relation to treatment guidelines and the economic burden of discordance with guidelines in a major referral Iranian university hospital. METHOD: Hospital records of hospitalized patients with empiric antibiotic prescription, from September 2016 to February 2017 were reviewed. The process consisted of comparing empiric antimicrobial administration with institutional guidelines for each patient by a clinical pharmacist and an infectious disease specialist to evaluate the appropriate utilization of antibiotics. Adherence to guideline, the cost of antibiotics usage for each patient and the excess cost consequent from discordance with guideline was calculated. RESULTS: The most inappropriate prescribed antibiotics were carbapenems and aminoglycosides. Overall guideline adherence was 27.8%. Frequency of antibiotic usage incompatibility with the guidelines on the basis of dosing interval, duration of therapy and drug indication were 31.46%, 29.44% and 19.36%, respectively. General surgery and internal medicine wards had the least and the most inappropriate antibiotic administration, respectively. Totally antibiotic usage cost was 578,959.39 USD (24,316,294,800 Iranian Rials, IRR) for 6 months, which the excess costs of inappropriate antibiotic prescribing, was 471,319.69 USD (19,795,427,225 IRR). The estimated annual excess cost is 942,639.38 USD (39,590,854,450 IRR). CONCLUSION: In this research, physicians' adherence with guidelines for empiric antibiotic therapy was low which was led to 471,319.69 USD excess costs. These results urge institution policy makers to develop guidelines to ensure active dissemination and implementation of them to decrease inappropriate antibiotic usage.

The Association Between Prolonged Proton Pump Inhibitors Use and Bone Mineral Density.

BACKGROUND AND STUDY AIM: Chronic use of proton-pump inhibitors (PPIs) has become a mainstay of therapy in common gastrointestinal diseases. A causal relationship between chronic PPI use and development of osteoporosis remains unproven. The aim of this study was to determine whether PPI users are more likely to develop alterations in bone density. PATIENTS AND METHODS: In an analytical cross sectional study, patients who used PPIs for more than 2 years because of long-term gastroesophageal reflux disease (GERD) were recruited. PPI users were healthy people except for GERD. The compression group was randomly derived from an age-, sex- and physical activity-matched group from a healthy population in the National Registry of Osteoporosis who had not used PPIs in the previous 2 years. Bone mineral density was measured with dual-energy X-ray absorptiometry. Data regarding BMD and bone mineral content (BMC) of three regions: femoral neck, total hip, and the lumbar spine (L1-L4) were gathered and recorded. The World Health Organization (WHO) classification was used for definition of osteopenia and osteoporosis. RESULTS: A total of 394 participants (133 PPI users and 261 comparison group) were enrolled. The median duration of PPI use was 6.7 (2-31) years. The mean age ± SD of PPI users and comparison group was 48.38 ± 11.98 and 47.86 ± years, respectively (P = 0.681). There was no significant difference in baseline characteristics and age distribution between the two groups. The BMC levels were significantly lower in PPI users in all three regions: lumbar spine, total hip, and femoral neck (P<0.001). There were no significant differences in the T-scores between the two groups except for femoral neck (P<0.001). Osteoporosis in femoral neck was significantly higher in PPI users than in comparison group. CONCLUSION: This study showed that long-term use of PPIs is associated with lower BMC and higher rate of osteoporosis in the femoral neck. However, more studies with longitudinal evaluation should be performed to clarify this causal relationship. Until then, it is advised not to overuse PPIs because of the possible increase in risk of osteoporosis and the risk of fractures. We also recommend using the BMC levels as a quantitative measure in addition to T scores in analysis and reporting similar studies.

Optimizing compliance with surgical antimicrobial prophylaxis guidelines in patients undergoing gastrointestinal surgery at a referral teaching hospital in southern Iran: clinical and economic impact.

BACKGROUND: Antibiotic prophylaxis is one of the major approaches to prevent surgical site infection. Despite the availability of international guidelines on it, the practice of antibiotic prophylaxis is still far from optimal. This study aimed to assess the impact of guideline implementation on the rational use of prophylactic antibiotics and its cost-saving effect in gastrointestinal surgery by clinical pharmacist intervention. METHODS: A pre and post intervention study was carried out between October 2017 and June 2018 on patients who underwent gastrointestinal surgery in a major referral teaching hospital in Shiraz, southern Iran. The intervention phase consisted of revising the institutional guidelines for surgical antimicrobial prophylaxis, assigning a clinical pharmacist to the surgical department, and arranging several meetings with the surgical department regarding the appropriate utilization of antibiotics. Differences in antibiotic utilization in patients before and after the intervention phase were compared. Exposures were surgical antimicrobial prophylaxis timing and agents, and main outcomes were incidence of surgical site infection and length of hospital stay. RESULTS: A total of 430 patients were included in the post intervention phase, while 445 patients were included in the baseline evaluation. Promoting appropriate antibiotic use in the post intervention group had the potential to decrease medication costs by reducing unnecessary prescriptions and duration of antibiotic usage (P<0.001). In the pre intervention group, the mean cost of antibiotic prescriptions was 11.5 times that of the post intervention group. Mean hospitalization in the pre intervention group was greater than the post intervention group (P<0.001). Furthermore, our data revealed that the rate of postsurgery infection in the post intervention group was 3.03%, while this rate was 6.76% in the preintervention group (P=0.01). CONCLUSION: This study provides evidence that adherence to surgical antimicrobial prophylaxis guidelines increased the rational use of prophylactic antibiotics, with substantial cost savings in patients who underwent surgery.

Association of ki67 and tumor marker p53 in locally advanced breast cancer patients and evaluation of response to neoadjuvant chemotherapy: a survey in South Iran.

PURPOSE: Heterogeneity of breast cancer, the most common cancer in women, complicates approach to its treatment. Neoadjuvant chemotherapy (NAC) in the treatment of locally advanced breast cancer (LABC) with the endpoint of achieving pathologic complete response (pCR) is not always successful. The purpose of this study was to evaluate the clinicopathologic characteristics, biomarker status and response of LABCs to NAC. PATIENTS AND METHODS: Core biopsies and post-surgical specimens of LABC patients were evaluated after receiving NAC. Their lymph node involvement, tumor staging, grading, size, tumoral and stromal lymphocytic infiltration (TLI, SLI), hormonal status, ki67, p53 and HER2 expression were evaluated. Response to NAC was assessed using pCR, Miller-Payne grading and residual cancer burden. RESULTS: In a total of 71 patients, pCR rate was 5.6%. Strong association was observed between ki67 positivity and p53 expression (P-value˂0.001). Also ki67, TLI and SLI showed association with triple negative tumor subtype (P-value 0.011, 0.002 and 0.014). Good response to NAC was associated with p53 expression. Nodal metastatic residue was also associated with primary tumor's nuclear grade. CONCLUSION: Strong correlation of ki67 and p53 can suggest probable interchangeability of both markers in the prognosis of LABC. In this study p53 even showed superiority to ki67 having association with good response. Strong association of ki67, TLI and SLI with triple negative tumor subtype can be parallel to an overall better response rate of this subtype. We can also propose the effectiveness of defining nuclear grade as a prognostic factor towards residual lymph node involvement post NAC.

Community pharmacists' knowledge, attitude, and practice of Irritable Bowel Syndrome (IBS): the impact of training courses.

Introduction: Irritable Bowel Syndrome (IBS) is a common chronic functional gastrointestinal disorder. Pharmacists have a vital role in patient education and in drug-therapy management for IBS. This survey is the first study in Iran, to evaluate knowledge, attitude, and practice (KAP) of community pharmacists on IBS, and the impact of training courses on the improvement of their skills. Objective and setting: This pre- and post-cross-sectional study was conducted to evaluate IBS-KAP amongst Community pharmacists in Shiraz, Iran. Methods: Pretested questionnaires were designed to assess professional characteristics and KAP components of the community pharmacists regarding IBS. All pharmacists from Shiraz were invited to participate in a 3-day training course on IBS. The participants were requested to complete the questionnaire before commencing the training course (pre-test), at the end of the 3-days course (post-test), and also 3 months after the course (follow-up test). Results: Correct answers to all parts increased after the training course, as well as in the follow-up stage, which was statistically significant in all three parts (P<0.05). The increases in correct answers were seen in the fields of attitude, practice, and knowledge. Conclusion: It seems that continuing IBS training courses are essential for pharmacists, regarding the fact that they can play an important role in assisting patients with IBS, as they are easily accessible healthcare professionals.