Variable Levels of Oxytocin During Sepsis: The Role of Oxytocin in Sepsis Pathophysiology.

BACKGROUND: Although the role of oxytocin in the pathophysiology of sepsis is still unknown, rising preclinical evidence suggests that oxytocin is possibly involved. However, no direct clinical studies have measured the levels of oxytocin during sepsis. In this preliminary study, the serum oxytocin levels were evaluated throughout the duration of sepsis. METHOD: Twenty-two male patients over 18 years of age with a SOFA score of 2 points or more who were admitted to the ICU were included. Patients with a history of neuroendocrine, psychiatric, and neurologic disorders, cancer, an infection caused by COVID-19, shock due to reasons other than sepsis, a history of psychiatric or neurologic medication use, and those who died during the study were excluded. The main endpoint included the measurement of serum oxytocin levels using radioimmunoassay at 6, 24, and 48 h of the ICU admission. RESULTS: Mean serum oxytocin level was higher at 6 h of ICU admission (41.27 ± 13.14 ng/L) than after 24 and 48 h of ICU admission (22.63 ± 5.75 and 20.97 ± 7.61 ng/L respectively) (P-value < .001). CONCLUSION: Our study, while reporting increased serum oxytocin levels in the initial phase of sepsis and decline afterward, supports the possible contribution of oxytocin in the pathophysiology of sepsis. Given that oxytocin seems to modulate the innate immune system, future investigations are necessary to assess the potential role of oxytocin in the pathophysiology of sepsis.

Aripiprazole for prevention of delirium in the neurosurgical intensive care unit: a double-blind, randomized, placebo-controlled study.

PURPOSE: Delirium is reported in over 50% of critically ill ICU patients, and is associated with increased mortality and long-term cognitive consequences. Prevention and early management of delirium are essential components of ICU care. However, pharmacological interventions have not been effective in delirium prevention. This study investigated the effect of aripiprazole in the prevention of delirium in a neurosurgical intensive care unit. METHODS: In this prospective, randomized placebo-controlled small clinical trial, 53 patients, 18 to 80 years old, were randomized to receive enteric aripiprazole (15 mg) or placebo for up to 7 days. Delirium, detected by the Confusion Assessment Method-ICU, ICU events, laboratory studies, aripiprazole safety, time to delirium onset, delirium-free days, delirium prevalence during follow-up and ICU length of stay were recorded. RESULTS: Forty patients with similar baseline characteristics, including age, sex, neurosurgery types and APACHE II scores, completed the study. Delirium incidence and the mean days to its onset were 20% vs. 55% (p = 0.022) and 2.17 ± 0.41 vs. 2.09 ± 0.30 (p = 0.076) in the aripiprazole and placebo groups, respectively. The mean number of delirium-free days were: 5.6 (95%CI, 4.6-6.5) and 4.3 (95%CI, 3.2-5.4), in aripiprazole and placebo groups, respectively (p = 0.111). The prevalence of delirium during the follow-up was significantly lower in the aripiprazole group (p = 0.018). Serious aripiprazole adverse reactions were not observed. CONCLUSIONS: Aripiprazole can reduce the incidence of delirium in the neurosurgical ICU. Studies with larger sample size in diverse ICU settings and longer follow-up are needed to confirm our findings.

Capecitabine induced fingerprint changes.

WHAT IS KNOWN AND OBJECTIVE: Fingerprinting is recognized as an easily accessible means of personal identification; however, fingerprints can be damaged after administration of some chemotherapy agents that result in hand and foot syndrome (HFS). Fingerprint loss may also be due to reasons unrelated to HFS. This study evaluated the incidence of fingerprint changes in patients treated with capecitabine-containing chemotherapy regimens and its relations to various grades of HFS. METHODS: Seventy-one patients who received chemotherapy with or without capecitabine as part of their regimen were enrolled in the study. Fingerprints were collected once before the initiation of chemotherapy and once after the third course of chemotherapy. The fingerprints were examined by the Iranian Society of Forensic Physicians, for probable changes in the post-chemotherapy states. RESULTS AND DISCUSSION: Thirty-seven patients were enrolled in the capecitabine group and 34 in a comparison group. Fingerprint changes were observed in 25 (67.6%) of the 37 patients in the capecitabine group and none in the comparison group. There was no correlation between the occurrence or severity of HFS and fingerprint changes (P = 0.880). In capecitabine group, the total dose and course numbers of capecitabine were not significant in patients with and without fingerprint changes. WHAT IS NEW AND CONCLUSION: Based on our findings, we recommend notifying patients who are considered for capecitabine therapy about the risk of fingerprint changes before the initiation of treatment, as this may have legal implications.

Management of Abnormal Placenta Implantation with Methotrexate: A Review of Published Data.

Abnormally invasive placenta is characterized by direct attachment of chorionic villi to the uterine wall. This adherent placenta traditionally has been managed by peripartum hysterectomy. Nowadays, there is a lot of interest toward gradual shift from traditional management of invasive placentation to conservative ones leaving the placenta in situ to avoid the surgical morbidity of hysterectomy and loss of future fertility. Administration of methotrexate (MTX), as an adjunctive antimetabolite drug, resulted in conflicting data during conservative management of abnormal placentation. This review assessed all published data on efficacy and safety of MTX therapy as conservative management of invasive placentation. Fifty-three articles including one prospective cohort study, 2 retrospective cohort studies, 10 case series and 40 case reports were identified. Conservative management has beneficial effects on the avoidance of major surgery with the consequent morbidity and the preservation of future fertility. Infection and vaginal bleeding were main complications of MTX therapy. Although MTX therapy may result in accelerated involution or expulsion of placenta and has some beneficial effects on hemorrhagic events, but there is not enough evidence on its efficacy and safety to recommend its routine uses in all cases of invasive placenta.

Oxaliplatin-induced renal tubular vacuolization.

OBJECTIVE: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. CASE SUMMARY: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of <1% schistocytes in the peripheral blood smear stood against the diagnosis of immune-mediated hemolytic anemia or hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Renal biopsy was consistent with interstitial nephritis with tubular vacuolization in favor of drug-induced renal injury. Based on the Naranjo Probability Scale, the likelihood of oxaliplatin-induced renal injury in this case was probable. DISCUSSION: To our knowledge, this is the first case report of renal tubular vacuolization with symptoms mimicking thrombotic microangiopathy in a patient on long-term chemotherapy with oxaliplatin. CONCLUSIONS: Oxaliplatin can induce various forms of nephrotoxicity such as renal tubular vacuolization, acute tubular necrosis, renal tubular acidosis, and acute kidney injury secondary to hematological toxicity. Monitoring for renal function abnormalities and hemolysis should be considered during oxaliplatin-based chemotherapy.

Surviving surgery; succumbing to pharmacotherapy: A case report underscoring the importance of PRN order clarification for patient safety.

"Pro re nata" (PRN) or "as needed" medicine administration and usage is a relatively neglected area in medication management (pharmacotherapy/pharmaceutical care) which contributes to error-prone use of medications and is unsafe for patients. In this case, we report the incident of diclofenac toxicity in a 51-year-old woman due to a prescription of 100 mg diclofenac suppositories PRN, or as needed, for postoperative pain control without explanation of the maximum daily dose (150 mg daily), which led to arbitrary consumption of 3 g of diclofenac over 5 days (600 mg daily) by the patient, and subsequent development of metabolic acidosis, acute kidney injury, and sudden cardiac arrest. The implementation of practical guidelines and training programs for health care workers to appropriately prescribe, dispense, and administer PRN medicines are necessary, and should at least include providing clarification for their indication, dose and frequency, as well as any cautionary instructions to ensure safe and effective use of such medicines.

A comparative study to assess the effectiveness of curcumin, mucosamin, and chlorhexidine in chemotherapy-induced oral mucositis.

BACKGROUND: Oral mucositis is one of the most frequent and challenging side effects of chemotherapy. At present, none of the guidelines recommend the use of various mouthwashes available for the treatment of oral mucositis. METHODS: This study was designed to evaluate the efficacy of curcumin, mucosamin, and chlorhexidine in the treatment of chemotherapy-induced oral mucositis. In this randomized and double-blind study, 71 patients over 18 years, who received chemotherapy and suffered from chemotherapy-induced oral mucositis, were randomized into curcumin, mucosamin, and chlorhexidine groups. The World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), and the Numerical Rating Scale (NRS) were used to evaluate oral mucositis. The main endpoint included the onset of complete recovery after starting the treatment. FINDINGS: Based on the WHO, OMAS for erythema, and NRS criteria, complete recovery was achieved from the third day in the curcumin group, which was significantly earlier compared to the other two groups (P < 0.05). The OMAS score for ulceration represented an improvement from day 5 in the curcumin group, which was significantly faster compared to the other two groups (P = 0.04). CONCLUSIONS: Our results indicated that all three approaches were effective in improving oral mucositis; however, curcumin could result in faster recovery in comparison with mucosamin and chlorhexidine. The use of curcumin in the treatment of oral mucositis appears to be a viable intervention for reducing potential compromise to treatment and improving the quality of life.

Efavirenz severe hypersensitivity reaction: case report and rapid desensitization protocol development.

OBJECTIVE: Long-term efavirenz desensitization protocols have been reported; however, publication of a rapid desensitization protocol has not been noted to date. We report a case of severe hypersensitivity reaction that was successfully managed using a rapid desensitization protocol. CASE SUMMARY: In a 52-year old HIV-positive woman, antiretroviral therapy was started with lamivudine 150 mg twice daily, zidovudine 300 mg twice daily, and efavirenz 600 mg daily. Nine days after starting antiretroviral therapy, she developed a generalized maculopapular rash. Despite concomitant chlorpheniramine administration, the rash did not improve. With suspicion of efavirenz hypersensitivity reaction, efavirenz was discontinued for 5 days and when the patient's rash resolved, the drug was restarted at 600 mg daily. The patient developed a severe generalized pruritic rash the next day and all antiretroviral agents were discontinued. One week later, lamivudine and zidovudine were restarted and were well tolerated. An OBJECTIVE: 20,000 solution of the target therapeutic dose, was successful. The patient was followed for 6 weeks and had no further signs or symptoms of a hypersensitivity reaction. DISCUSSION: Efavirenz hypersensitivity reactions typically include cutaneous reactions that are observed in the first 2 weeks of treatment, are often mild to moderate without systemic manifestation, and improve with continued therapy. Previously, successful desensitization protocols have been described in patients receiving efavirenz who developed rash without systemic symptoms, but these protocols were carried out over 7 or 14 days. This case report indicates a rapid desensitization protocol that may be an available option for some patients. CONCLUSIONS: Considering that efavirenz can be the cornerstone of many antiretroviral therapy regimens and hypersensitivity reactions can restrict regimen options, effective desensitization protocols are valuable, especially in the developing countries with limited available antiretroviral drugs.

An Open-Label, Single-Arm, Pilot Intervention Study to Assess the Efficacy and Safety of Apixaban in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction due to its related risk of life- and limb-threatening thrombosis. Apixaban is a direct factor Xa inhibitor that may be intended as an ideal alternative for the management of HIT. In this open-label, single-arm, pilot intervention study, the efficacy and safety of apixaban were evaluated in 30 patients aged >18 years with clinically suspected HIT (4Ts score ≥4 points). Patients with mechanical heart valves, chronic kidney disease, hepatic impairment, and active bleeding were excluded. In all patients with inclusion criteria, heparin or enoxaparin was discontinued and apixaban was started. The dose of apixaban for HIT suspected patients was defined on the basis of the reason for anticoagulant therapy. End points included confirmed thrombosis, mortality, and adverse treatment-related events. After apixaban therapy, platelet counts normalized in all patients; none of the 30 subjects developed new, progressive, or recurrent thrombosis; and only 1 of 30 patients developed a hemorrhagic event. Five patients (16.7%) died, but the reason for death was not linked to thrombosis, hemorrhage, or adverse effects of apixaban. Along with the available emerging data, our results propose that apixaban could be a safe and effective drug for the management of suspected HIT in clinically stable patients.

Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a high-risk adverse drug reaction because of its associated risk of life- and limb-threatening thrombosis. Rivaroxaban may be considered as an ideal nonheparin anticoagulant alternative for the management of HIT. In this preliminary retrospective study, the efficacy and safety of rivaroxaban to control the clinically suspected HIT (4Ts score 4 points or greater) were evaluated. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, and active bleeding were excluded. Forty-two eligible patients who received rivaroxaban for clinically suspected HIT were evaluated by medical records review, with 12-month follow-up after the first dose of rivaroxaban. End points included confirmed thrombosis (primary end point), mortality, and adverse treatment-related events. HIT-associated thrombosis was found in 17/42 (40.5%) patients before receiving rivaroxaban. After rivaroxaban therapy, platelet counts normalized in all patients, with only 1/42 (2.3%) patients developing new thrombosis. No hemorrhagic event was recorded in the patients. Twelve patients (28.6%) died, but the cause of death was not related to the thrombosis, hemorrhage, or adverse effects of rivaroxaban. Our findings are consistent with the available emerging data, suggesting that rivaroxaban is a safe and effective drug for the management of clinically suspected HIT. Rivaroxaban is a particularly valuable treatment option in developing countries, where there are issues of cost and availability of approved alternative agents.

Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially serious adverse drug reaction that can result in lethal vascular thrombosis. Dabigatran is a direct thrombin inhibitor that might be useful in the management of HIT. This study evaluated the efficacy and safety of dabigatran in patients with HIT. We included 43 patients in the study who received dabigatran for the management of suspected HIT, based on 4Ts (thrombocytopenia, timing of platelet count drop, thrombosis or other sequelae, and other causes of thrombocytopenia) scores. Three patients were excluded because they had received dabigatran with a creatinine clearance <15 mL/min. Patients' records were analyzed longitudinally, with 12 months follow-up from the time of initiation of dabigatran, for occurrence of thrombosis, dabigatran-related complications, and outcome. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, active bleeding, and extremes of weights (<50 and >120 kg) were excluded from the study. Arterial thrombosis was not observed in any of our patients. The platelet counts normalized in all patients except for 2, which was attributed to the underlying comorbidities. We did not observe any hemorrhagic events or significant thrombosis during the follow-up period. Eight patients died from nonthrombotic causes, which were unrelated to adverse effects of dabigatran. Based on our findings, dabigatran could be considered a safe and effective agent in the management of HIT, particularly in the developing countries, where there could be issues with the cost and availability of other agents recommended for this condition. Further studies are needed to validate our findings.

Intravenous Immunoglobin Utilization Study in a Teaching Hospital.

BACKGROUND: Intravenous immunoglobulin (IVIG) is an immunomodulating agent that has several actions. The aim of this study was to investigate the indications of IVIG according to available evidence and the cost in our center. METHODS: This retrospective study was conducted between September 2017 and June 2018 at a teaching hospital affiliated with Iran University of Medical Sciences, Tehran, Iran. Patients' demographic data and disease, indication for IVIG use, its dosage and treatment regimen and previous and concurrent treatments were assessed. The collected data were compared with the present criteria for the pattern of IVIG usage. The last version of Lexicomp® was used as the reference for indications of the administrated drug and its dosage. RESULTS: A total of 119 patients received IVIG during the study period. The wards with the most frequent IVIG prescription were the neurology (46.2%) and neonatal intensive care unit (21%). The most common reasons of IVIG therapy were various inflammatory neurological disorders. IVIG was used in 22, 43 and 54 cases according to on-label, off- label and other indications, respectively. The total price was higher for off-label indications for IVIG ($254343.75) than on-label indications ($152625). As well, $107250 was exhausted for cases in which there was not sufficient evidence. CONCLUSION: One important aspects of this study was the use of IVIG in cases other than on-label indications. Although a number of studies support IVIG therapy in some diseases, further trials are needed to establish efficacy and safety in these fields.

Epidemiological Survey of Human Dermatophytosis due to Zoophilic Species in Tehran, Iran.

BACKGROUND: Dermatophytosis is known as one of the most frequent cutaneous infections that lead to public health problems to human and animals. The purpose of this study was to determine the prevalence of human dermatophytosis due to zoophilic species in Tehran, Iran from 2014 to 2015. METHODS: Overall, 3989 patients with clinically suspected fungal infections were studied. Samples of skin, hair, and nails were examined by direct examination and culture. Direct microscopic examination was performed by KOH 15% for skin, KOH and DMSO for nail clippings and lactophenol for hair. Specimens were cultured on Sabouraud dextrose agar and mycobiotic agar. RESULTS: Of 3989 patients, 755 (19%) suffered from dermatophytosis. Out of isolated dermatophytes, 716 (94.8%) anthropophilic, 35 (4.6%) zoophilic and 4 (0.5%) were geophilic species. Among of 35 patients with zoophilic dermatophyte infections, 65.7% were female. The most common type of zoophilic dermatophytosis according to anatomical areas was tinea manuum (34.3%) followed by tinea faciei (22.9%), tinea pedis (20%). Trichophyton verrucosum (57.1%) was the most commonly causative agents of zoophilic dermatophyte infections followed by Microsporum canis (42.9%). CONCLUSION: Our study showed epidemiological trends in the etiology of the agents causing dermatophytosis have changed in Tehran. Although the prevalence of zoophilic species declined in recent years, due to the tendency of most people to change lifestyles and increased urbanization, promotion of public health care and identification of new preventive and therapeutic strategies are necessary.

Albumin Utilization Evaluation in a Major Teaching Hospital in Iran: Recommendations for Guideline Development.

OBJECTIVE: Human albumin solution is an expensive colloidal preparation which is commonly used in clinical practice. Due to high cost of albumin, increased rate of the inappropriate use worldwide, and many other reasons, it is imperative to establish a practical protocol to use albumin products and limit its usage. The aim of this study was to identify albumin utilization patterns in a teaching hospital and to demonstrate the importance of the need to reconsider prescribing strategies for albumin administration. METHODS: This retrospective cross-sectional study was performed between August 2016 and December 2016 at Firoozgar Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran. All albumin prescriptions for adult patients during the study period were enrolled for appropriateness evaluation according to the latest evidence-based studies and guidelines. FINDINGS: Among 320 albumin prescriptions, 168 (52.5%) were inappropriate according to the current evidence. The most common irrational causes for the albumin usage were hypoalbuminemia (23.4%), nutritional support (13.7%), neuroprotection in subarachnoid hemorrhage (3%), pretreatment for cancer surgery (2.8%), edema (1.6%), hepatic failure (1.6%), and paracentesis (3%). The total amount of albumin used for 320 patients was 52,050 g, from which 28,470 g was inappropriate resulting in $97,398 wastage. CONCLUSION: These findings, along with aforementioned guidelines, support the requirement for physicians' educational programs and proper strategies for appropriate prescriptions and could also be important in modifying the available guidelines concerning expensive drugs such as albumin.

Antipyretic Effect of Clonidine in Intensive Care Unit Patients: A Nested Observational Study.

Fever in the intensive care unit (ICU) is usually an adaptive response to infection or inflammation. Pharmacological intervention is often required in addition to addressing the underlying causes of fever. Animal studies have examined the antipyretic effect of clonidine; however, to our knowledge there are no clinical data available in humans. The observation of an antipyretic effect of clonidine was made during a single-center randomized control trial that was designed to study the effect of clonidine addition to the commonly used sedative agents in mechanically ventilated ICU patients. Forty patients 18 years or older on mechanical ventilation for 3 days or longer were randomized into 2 groups receiving clonidine and placebo. In addition to the usual sedation/analgesia, patients in the clonidine arm received enteral clonidine in doses of 0.1 mg 3 times a day (TID), which was increased to 0.2 mg TID if the hemodynamics remained stable. Vital signs, laboratory data, all cultures, and daily ICU events were recorded. The odds ratio of temperature higher than 38.3°C was 3.96 times higher in the placebo group, after adjustment for the illness severity and the time of follow-up (P = .049). A lower temperature (0.52°C) was observed in the clonidine group after adjustment for the time of follow-up (P = .006). Our report is the first of its kind in humans that demonstrates possible antipyretic properties of enteral clonidine in the critically ill intensive care unit patient.

The Content of Plasma Selenium in Early Admitted Septic Patients.

OBJECTIVE: Selenium depletion has been reported in critical illness correlates with an increase in mortality and morbidity. In this study, we aimed to access the selenium plasma levels of septic patients early at the Intensive Care Unit (ICU) admission in order to compare with reference range. METHODS: We conducted a cross-sectional study in a university affiliated hospital aiming to assess the early plasma level of selenium in ICU admitted patients. eighty patients diagnoses with sepsis were included and considered for characteristic evaluation, monitoring criteria assessment and also blood sampling. All blood sampling was performed during 48 hours of the ICU admission in order to determined the plasma Selenium level by atomic absorption method. FINDINGS: The mean plasma levels of selenium in male and female was 98.14 ± 23.52 and 78.1 ± 24.46 µ/L, respectively. Although selenium plasma levels was higher in the ICU male patients significantly, both had near normal range (80 µ/L). CONCLUSION: In this study we found that in early admitted Iranian ICU patients in Tehran, selenium deficiency has not routinely seen but probably will happen during ICU hospitalization.

Fingerprint changes among cancer patients treated with paclitaxel.

BACKGROUND: Fingerprints have long been used for personal identification; however, some case reports suggested that some chemotherapy agents such as paclitaxel lead to fingerprints loss due to hand-and-foot syndrome (HFS). METHODS: This case-control study was performed on 65 patients who received chemotherapy regimens with/without paclitaxel. Patients with the history of receiving any drugs with significant HFS adverse effect or patients with any conditions that affect fingerprints were excluded. Baseline and post-chemotherapy images of fingerprint examples were referred to the Iranian Society of Legal Medicine to compare changes in the fingerprints. RESULTS: Thirty-one patients entered in the paclitaxel and 34 subjects in the control groups. Seventeen patients (54.8%) in the paclitaxel group experienced fingerprint changes, whereas no patient had fingerprint changes in the control group. By physical examination, no patients in the two groups experienced HFS. After adjusting for age, sex, occupation, and cancer type, there was a significant difference between the two groups regarding fingerprint changes (P = 0.002, OR 13.69, 95% CI 2.05 to infinite). CONCLUSIONS: Considering that fingerprint recognition has been utilized in both government and civilian investigation, patients taking paclitaxel and centers necessitating fingerprint identification should be informed about possible fingerprint changes by paclitaxel.