Prognosis of Methanol Poisoning in a Developing Setting.

BACKGROUND: Methanol-poisoning can be a challenging cause of mortality. Identifying the epidemiological, clinical, and para-clinical determinants of outcome in methanol-poisoning patients could be a step forward to its management. METHODS: In this hospital-based cohort study, 123 methanol-poisoning patients were included. Data on background variables, details of methanol consumption, and laboratory assessments were recorded for each patient. Patients underwent brain CT scans without contrast. We evaluated the association of all gathered clinical and para-clinical data with patients' outcome and length of hospital stay (LOS). Independent association of potential determinants of death, and LOS were modeled applying multivariable logistic, and Ordinary Least Square regressions, respectively. Odds ratio (OR), and regression coefficient (RC), and their 95% confidence intervals (CIs) were estimated. RESULTS: Most of the study population were male (n=107/123). The mean age of the participants was 30.3±9.1 years. Ninety patients (73.2%) were reported as being conscious on admission, and 34.3% of patients were identified with at least one abnormality in their CT scan. Level of consciousness (LOC) (OR: 42.2; 95% CI: 2.35-756.50), and blood pH (OR: 0.37; 95% CI: 0.22-0.65) were associated with death. Supratentorial edema (RC: 17.55; 95% CI: 16.95-18.16) were associated with LOS. CONCLUSION: Besides LOC, patients with any abnormality in their brain CT scan on admission were found to be at higher risk of death, and patients with supratentorial edema were at risk of longer LOS. Brain CT-scan on admission should be considered as a part of the routine procedure during the management of methanol-poisoning.

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.

Osteoma in the upper cervical spine: A case report and comprehensive literature review.

INTRODUCTION AND IMPORTANCE: Osteoma is a benign, and usually asymptomatic bone tumor normally found in the skull and facial bones, although it can occasionally occur in the long bones and spine. CASE PRESENTATION: In this article, we present a 49-year-old male patient who experienced progressive neck pain accompanied by left-sided radicular pain symptoms. Clinical investigation using various imaging techniques confirmed a bone-forming lesion located within the C1 vertebrae region. Treatment involved performing hemilaminectomy of C1 along with resection for complete removal of this extradural bone lesion, ultimately achieving symptom relief. Histopathological examination of the resected specimen leads to the diagnosis of osteoma. Along with reporting this case, we conducted a comprehensive literature review of the previously reported spinal osteoma cases. CLINICAL DISCUSSION: Histopathological examination confirmed the diagnosis of osteoma. A comprehensive literature review was conducted, revealing 16 previously reported cases of spinal osteoma. Among these, only one case involved the C1 vertebra and presented similar neurological symptoms. The review underscores the rarity of spinal osteomas and the importance of surgical intervention for symptom relief. CONCLUSION: Spinal osteomas are rare but should be considered in the differential diagnosis of patients presenting with neck pain and radicular symptoms. Surgical removal of the lesion is often necessary for symptom relief, as highlighted by our case and supported by the literature review. This case adds to the limited body of evidence on spinal osteomas and emphasizes the importance of a multidisciplinary approach for optimal patient outcomes.

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID-19 patients: A systematic review and meta-analysis.

Background and Aim: Due to the high social and economic burden and also mortality and morbidity caused by coronavirus disease 2019 (COVID-19) in the past few years, researchers have aimed at finding solutions to suppressing the severity of infection. Recently, selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) have been investigated as an adjuvant treatment for COVID-19. The aim of the current study was to investigate the impact of SSRI/SNRIs on outcomes of COVID-19 patients. Methods: In this systematic review and meta-analysis, a comprehensive search strategy consisting of relevant words was performed by two researchers in PubMed, Scopus and EMBASE libraries. Studies reporting the effect of SSRI and/or SNRI use in COVID-19 patients' outcome were included. Hospitalization, mortality, hospitalization event, and length of hospital stay were considered as main outcomes of this study. Analysis was carried out using Comprehensive Meta-Analysis (CMA-version 2) and final data were reported as odds ratio (OR) and 95% confidence interval (CI). Results: Our search led to the final selection of 9 articles including 15,287 patients. The effect of fluvoxamine, fluoxetine, and the overall effect of SSRI/SNRI use on mortality of COVID-19 patients were investigated in 3, 2, and 7 articles, respectively. The results of our analyses showed that these medications could significantly decrease mortality of COVID-19 patients (OR and 95% [CI]: 0.595 [0.467-0.758], 0.620 [0.469-0.821], and 0.596 [0.437-0.813]). The effect of SSRI/SNRIs on hospitalization events of COVID-19 patients was not significant (OR: 0.240% and 95% CI: 0.041-1.4). Also, length of hospital stay was longer in patients who administrated SSRIs. Conclusion: According to this study's results, SSRI/SNRIs may be effective in reducing mortality of COVID-19 patients, suggesting the superiority of fluvoxamine to fluoxetine. The safety profile and affordable cost of SSRI/SNRIs for a short-term use may be other reasons to propose them as beneficial medications in preventing mortality in COVID-19.

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.

SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease.

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR-RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4-15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05-6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05-35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4-12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73-4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2-3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7-10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4-9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.

PathoNet introduced as a deep neural network backend for evaluation of Ki-67 and tumor-infiltrating lymphocytes in breast cancer.

The nuclear protein Ki-67 and Tumor infiltrating lymphocytes (TILs) have been introduced as prognostic factors in predicting both tumor progression and probable response to chemotherapy. The value of Ki-67 index and TILs in approach to heterogeneous tumors such as Breast cancer (BC) that is the most common cancer in women worldwide, has been highlighted in literature. Considering that estimation of both factors are dependent on professional pathologists' observation and inter-individual variations may also exist, automated methods using machine learning, specifically approaches based on deep learning, have attracted attention. Yet, deep learning methods need considerable annotated data. In the absence of publicly available benchmarks for BC Ki-67 cell detection and further annotated classification of cells, In this study we propose SHIDC-BC-Ki-67 as a dataset for the aforementioned purpose. We also introduce a novel pipeline and backend, for estimation of Ki-67 expression and simultaneous determination of intratumoral TILs score in breast cancer cells. Further, we show that despite the challenges that our proposed model has encountered, our proposed backend, PathoNet, outperforms the state of the art methods proposed to date with regard to harmonic mean measure acquired. Dataset is publicly available in http://shiraz-hidc.com and all experiment codes are published in https://github.com/SHIDCenter/PathoNet .

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.

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.

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.

Impact of Clinical Pharmacist's Interventions on Potential Drug-Drug Interactions in the Cardiac Care Units of Two University Hospitals in Shiraz, South of Iran.

OBJECTIVE: The main objective of this study aimed to assess drug-drug interactions (DDIs) in the cardiac care unit (CCU) and cardiac surgery units and the role of a clinical pharmacist in detecting and preventing the expected DDIs. METHODS: This cross-sectional study was conducted in the CCU Units of Nemazee and Shahid Faghihi Hospitals, two referral hospitals in Shiraz, South of Iran, from August to February 2016. Patients older than 18 years, who were admitted and had received >24 h of inpatient services in these wards with two or more medication orders, were included in this study. All medication orders were evaluated by a pharmacist and DDIs were examined based on the Lexi-Interact™ software. In cases with serious DDIs (D or X), the physicians and nurses were informed, and intervention was conducted by a clinical pharmacist. FINDINGS: A total of 3706 medical orders were evaluated. 6478 DDIs were detected, of which, 446 (6.88%) belonged to Classes D and X, and a total of 43.43% of all hospitalizations had at least one DDI. Factors with the most considerable influence on DDIs included an increased number of prescribed medications and patients underlying disease. The physicians accepted 62% of the interventions. The most frequent drugs responsible for interactions of Classes C, D, and X were aspirin, warfarin, and clopidogrel, respectively. CONCLUSION: This study shows that a significant number of clinical DDIs exist in hospitalized patients, especially among consumers of warfarin and aspirin. The role of a clinical pharmacist in preventing such interactions and safer pharmacotherapy management for hospitalized patients is essential.

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.

Response to sertraline is influenced by GNß3 gene G-350A variant in patients with major depressive disorder.

PURPOSE: Heterotrimeric guanine nucleotide-binding proteins (G proteins) are a major group of human genome membrane protein receptors. Genetic variation in the ß3 subunit (GNß3) associated with gene splicing and increased activity is associated with major depressive disorder (MDD). However, the effect of G-350A GNß3 genetic polymorphism and therapeutic outcome of selective serotonin reuptake inhibitors (SSRIs) in MDD has not yet been studied. METHOD: One hundred newly diagnosed MDD patients were treated with sertraline for 6 weeks. The severity of depressive symptoms was weekly assessed by Hamilton Rating Scale for Depression (HRSD). A 50% decrease in HRSD was defined as response to treatment. GNß3 polymorphisms (G-350A, A657T) were determined in each individual using a PCR-RFLP technique. RESULTS: Our results suggested that subjects with GG genotype of G-350A responded 5.9-folds more to sertraline compared to carriers of other variants (P = 0.004, OR = 5.9; 95% CI = 1.66-21.99). In addition, carriers of the G allele responded 1.9-folds more to sertraline than carriers of the A allele (P = 0.032, OR = 1.92; 95% CI = 1.05-3.65). However, no association was observed between A657T variants and response to sertraline (P = 0.920, OR = 0.9; 95% CI = 0.31-2.69). CONCLUSION: The results suggest that G-350A variant of GNß3 plays a foremost part as a predictor of response to antidepressant treatment.

Evaluating Adherence of Health-Care Team to Standard Guideline of Colistin Use at Intensive Care Units of a Referral Hospital in Shiraz, Southwest of Iran.

Purpose: To evaluate colistin use according to global standard drug consumption in intensive care units of a referral hospital in Shiraz, Iran Methods: A prospective, interventional study was performed during an 11 month period on 100 patients admitted to ICUs of a teaching hospital being treated with colistin for at least 3 subsequent doses. Required demographic, clinical, and paraclinical data were gathered by a pharmacist. Fifteen indexes were considered to evaluate colistin use. A clinical pharmacist reviewed indication and dose of colistin at the time of prescribing this agent. Results: In our study population, pneumonia (69%) was the main indication of colistin. In 87% of patients, colistin administration was based on microbiological laboratory evidence. Continuation of therapy was inappropriate in 5% of cases. By the intervention of the clinical pharmacist, colistin was discontinued in all patients in whom empirical therapy was continued incorrectly. None of the patients received loading dose of colistin. The maintenance dose, dose interval, and duration of treatment of colistin were appropriate in 76%, 71%, and 100% of patients, respectively. For none of the patients, the pharmacokinetic dosing method was used. In all patients, serum creatinine and WBC count were evaluated on daily basis. The sum indexes of colistin use were relevant to standard guidelines in 67.33% of the cases. Conclusion: The results of this study highlight the necessity of the pharmaceutical care team participation in all stages of treatment with antibiotics. After pharmacist interventions, some criteria of colistin utilization were corrected and brought closer to standard values.

Health Care Workers' Knowledge, Attitude, and Practice About Chronic Pain Management, Shiraz, Iran.

BACKGROUND: Pain can adversely affect every aspect of a patient's daily activity, and consequently, it has a great influence on the quality of life. Studies have shown that health care professionals have little knowledge of and inadequate attitudes toward the assessment of pain and its treatment with analgesics. OBJECTIVES: This cross-sectional study was designed to evaluate the knowledge, attitudes, and practice of health care professionals regarding chronic pain management. It was carried out in six different educational hospitals affiliated with Shiraz University of Medical Sciences in Shiraz, Iran. PATIENTS AND METHODS: Participants were given a questionnaire containing 46 questions and demographic characteristics to fill out independently. In total, 213 health care professionals (114 nurses and 99 medical residents) volunteered to take part in this study. In order to ease further analysis, the questions were grouped into three categories: narcotic drugs, non-narcotic drugs, and non-drug-related questions. RESULTS: The mean correct response rate was 43.13% ± 11.10. Medical residents scored 51.23% ± 9.02% and nurses 36.10% ± 7.31% (P < 0.001). There was no statistically significant relation between field of specialty and the mean scores of medical residents. Narcotic drug questions received the lowest (39.02%) and non-narcotic drug questions received the highest (57.32%) percentages of correct responses. Only 9.3% of participants believed that they had received adequate education about pain and its management. CONCLUSIONS: The findings of this study support concern about inadequate knowledge, attitudes, and practice regarding chronic pain management. We believe that further education and practical training will be needed for adequate pain management.