Case Report: Life-Threatening Fluoxetine-Linked Postoperative Bleeding Informed by Pharmacogenetic Evaluation.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRI) are commonly used for the treatment of depression and anxiety. Inhibition of serotonin reuptake in platelets increases bleeding risk in patients taking SSRIs. CASE: Here, we present the case of a 52-year-old patient who developed severe postsurgical bleeding requiring blood transfusion following panniculectomy. CONCLUSION: SSRI-induced bleeding is dose-related and strongly influenced by individual variations in drug metabolizing enzymes and transporters. Supplementary file1 (MP4 8441 KB).

The Pattern of Admission, Clinical Characteristics, and Outcomes Among Patients Admitted to the Intensive Care Unit of a Tertiary Hospital in Tanzania: A 5-Year Retrospective Review.

Introduction: Despite the implementation of complex interventions, ICU mortality remains high and more so in developing countries. The demand for critical care in Sub-Saharan Africa is more than ever before as the region experiences a double burden of rising rates of non-communicable diseases (NCD) in the background battle of combating infectious diseases. Limited studies in Tanzania have reported varying factors associated with markedly high rates of ICU mortality. Investigating the burden of ICU care remains crucial in providing insights into the effectiveness and challenges of critical care delivery. Material and Methods: A single-center retrospective study that reviewed records of all medically admitted patients admitted to the ICU of the Aga Khan Hospital, Dar-es-Salaam, from 1st October 2018 to 30th April 2023. To define the population in the study, we used descriptive statistics. Patients' outcomes were categorized based on ICU survival. Binary logistic regression was run (at 95% CI and p-value < 0.05) to identify the determinants for ICU mortality. Results: Medical records of 717 patients were reviewed. The cohort was male (n=472,65.8%) and African predominant (n=471,65.7%) with a median age of 58 years (IQR 45.0-71.0). 17.9% of patients did not survive. The highest mortality was noted amongst patients with septic shock (29.3%). The lowest survival was noted amongst patients requiring three organ support (n=12,2.1%). Advanced age (OR 1.02,CI 1.00-1.04), having more than three underlying comorbidities (OR 2.50,CI 1.96-6.60), use of inotropic support (OR 3.58,CI 1.89-6.80) and mechanical ventilation (OR 9.11,CI 4.72-18.11) showed association with increased risk for mortality in ICU. Conclusion: The study indicated a much lower ICU mortality rate compared to similar studies conducted in other parts of Sub-Saharan Africa. Advanced age, underlying multiple comorbidities and organ support were associated with ICU mortality. Large multi-center studies are needed to highlight the true burden of critical care illness in Tanzania.

Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses.

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity. METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models. DISCUSSION: It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations.

Randomized controlled trials are considered the 'gold standard' to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.

Comparison of DNA vaccines with AS03 as an adjuvant and an mRNA vaccine against SARS-CoV-2.

Emerging variants of SARS-CoV-2 call for frequent changes in vaccine antigens. Nucleic acid-based vaccination strategies are superior as the coding sequences can be easily altered with little impact on downstream production. mRNA vaccines, including variant-specific boosters, are approved for SARS-CoV-2. Here, we tested the efficacy of DNA vaccines against the SARS-CoV-2 Spike aided by the AS03 adjuvant using electroporation and compared their immunogenicity with an approved mRNA vaccine (mRNA-1273). DNA vaccination elicited robust humoral and cellular immune responses in C57BL/6 mice with Spike-specific antibody neutralization and T cells produced from 20 µg DNA vaccines similar to that from 0.5 µg mRNA-1273. Furthermore, a Nanoplasmid-based vector further increased the immunogenicity. Our results indicate that adjuvants are critical to the efficacy of DNA vaccines in stimulating robust immune responses against Spike, highlighting the feasibility of plasmid DNA as a rapid nucleic acid-based vaccine approach against SARS-CoV-2 and other emerging infectious diseases.

Magnitude, Distribution and Contextual Risk Enhancing Predictors of High 10-Year Cardiovascular Risk Among Diabetic Patients in Tanzania.

Introduction: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of death worldwide. In Diabetics, ASCVD is associated with poor prognosis and a higher case fatality rate compared with the general population. Sub-Saharan Africa is facing an epidemiological transition with ASCVD being prevalent among young adults. To date, over 20 million people have been living with DM in Africa, Tanzania being one of the five countries in the continent reported to have a higher prevalence. This study aimed to identify an individual's 10-year ASCVD absolute risk among a diabetic cohort in Tanzania and define contextual risk enhancing factors. Methods: A prospective observational study was conducted at the Aga Khan hospital, Mwanza, for a period of 8 months. The hospital is a 42-bed district-level hospital in Tanzania. Individuals 10-year risk was calculated based on the ASCVD 2013 risk calculator by ACC/AHA. Pearson's chi-square or Fischer's exact test was used to compare categorical and continuous variables. Multivariable analysis was applied to determine contextual factors for those who had a high 10-year risk of developing ASCVD. Results: The overall cohort included 573 patients. Majority of the individuals were found to be hypertensive (n = 371, 64.7%) and obese (n = 331, 58%) having a high 10-year absolute risk (n = 343, 60%) of suffering ASCVD. The study identified duration of Diabetes Mellitus (>10 years) (OR 8.15, 95% CI 5.25-14.42), concomitant hypertension (OR 1.82 95% CI 1.06-3.06), Diabetic Dyslipidemia (OR 1.44, 95% CI 1.08-1.92) and deranged serum creatinine (OR 1.03, 95% CI 1.02-1.03) to be the risk enhancing factors amongst our population. Conclusion: The study confirms the majority of diabetic individuals in the lake region of Tanzania to have a high 10-year ASCVD risk. The high prevalence of obesity, hypertension and dyslipidemia augments ASCVD risk but provides interventional targets for health-care workers to decrease these alarming projections.

Clinical and Economic Impact of Rapid Blood Pathogen Identification Via Verigene.

INTRODUCTION: Bloodstream infections (BSIs) are associated with increased morbidity and mortality if not treated appropriately. Rapid identification of microorganisms will allow clinicians the opportunity to modify initial broad-spectrum antibiotic therapy and improve patient outcomes in bacteremia. We aim to evaluate the impact of the Verigene Gram-positive blood culture (BC-GP) technology on time to modification of antibiotic therapy by clinicians. METHODS: This was a retrospective research study conducted at Corpus Christi Medical Center. Verigene BC-GP technology was employed to rapidly identify microorganisms in patients with suspected Gram-positive bacteremia. Empiric antibiotic therapy was modified via de-escalation or escalation when culture results became available. The primary outcome for this study was the mean time to modification of antibiotic therapy after Verigene BC-GP results became available. Data analysis was conducted from data collected between January 2015 and August 2017 to assess the clinical and pharmacoeconomic impact of BC-GP. RESULTS: Data were collected on 159 patients, with 123 of 159 (77%) meeting the inclusion criteria. The mean age was 66 ± 14.9 years, with 53/123 (43%) females and 70/123 (57%) males. Positive cultures identified were as follows: Streptococcus species (34), Staphylococcus species (72), 31/72 (43%) were MRSA, and Enterococcus species (19), 4/19 (21%) were Vancomycin-resistant Enterococcus (VRE). Antibiotic therapies in 31 of 123 patients (25%) were escalated, and 29 of 123 (24%) were de-escalated. Therapy was determined to be appropriate based on culture results in 63 of 123 (51%) patients, and thus therapy was not modified in this group. The mean time to escalate therapy was 6.2 ± 6 h and 9.2 ± 12.1 h to de-escalate. The average time for modification of antibiotic therapy was 7.6 ± 9.5 h. The conventional approach would take approximately 24-72 h for pathogen identification. Data on cost savings per intervention is estimated to be approximately $4000 per intervention. Based on this model, we estimate approximately $240,000 in cost savings from the 60 cases where interventions occurred. CONCLUSION: There is a significant time advantage to pathogen identification, therapy modification as well as a pharmacoeconomic benefit associated with the Verigene GC-GP system as compared to the conventional approach, which translates to positive patient outcomes.

Case Report Highlighting Cardiovascular Effects of Concomitant Use of Methamphetamine and Marijuana.

We present the case of a 51-year-old male admitted for cardiovascular complications in the face of concomitant chronic methamphetamine and cannabis use. Upon further assessment, the patient exhibited cardiotoxicity, including acute to chronic congestive heart failure (CHF) exacerbation, hypercoagulable state, and electrolyte abnormalities. Cardiotoxicity secondary to chronic methamphetamine use has been established. However, marijuana's cardiovascular effects have not been well established. Even less information exists about the simultaneous use of methamphetamine and cannabis. With increasing interest in the use of marijuana for medical purposes, it is imperative to study any corresponding toxicity and adverse effect profile. The worldwide pattern of drug co-administration also brings the importance of this topic to light. This case report serves to provide insight into this information gap.

Drug-Induced Hyperthermia Review.

Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs. EHS is a syndrome characterized by hyperthermia and the activation of systemic inflammation. Several drug-induced hyperthermic syndromes may resemble EHS and share common mechanisms. The purpose of this article is to review the current literature and compare exertional heat stroke (EHS) to three of the most widely studied drug-induced hyperthermic syndromes: malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). Drugs and drug classes that have been implicated in these conditions include amphetamines, diuretics, cocaine, antipsychotics, metoclopramide, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and many more. Observations suggest that severe or fulminant cases of drug-induced hyperthermia may evolve into an inflammatory syndrome best described as heat stroke. Their underlying mechanisms, symptoms, and treatment approaches will be reviewed to assist in accurate diagnosis, which will impact the management of potentially life-threatening complications.

Overview of the Role of Pharmacological Management of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) remains a prominent disease state characterized by the recurrent collapse of the upper airway while sleeping. To date, current treatment may include continuous positive airway pressure (CPAP), lifestyle changes, behavioral modification, mandibular advancement devices, and surgical treatment. However, due to the desire for a more convenient mode of management, pharmacological treatment has been thoroughly investigated as a means for a potential alternative in OSA treatment. OSA can be distinguished into various endotypic or phenotypic classes, allowing pharmacological treatment to better target the root cause or symptoms of OSA. Some medications available for use include antidepressants, CNS stimulants, nasal decongestants, carbonic anhydrase inhibitors, and potassium channel blockers. This review will cover the findings of currently available and future study medications that could potentially play a role in OSA therapy.

Review of the Management of Obstructive Sleep Apnea and Pharmacological Symptom Management.

Nearly a billion adults around the world are affected by a disease that is characterized by upper airway collapse while sleeping called obstructive sleep apnea or OSA. The progression and lasting effects of untreated OSA include an increased risk of diabetes mellitus, hypertension, stroke, and heart failure. There is often a decrease in quality-of-life scores and an increased rate of mortality in these patients. The most common and effective treatments for OSA include continuous positive airway pressure (CPAP), surgical treatment, behavior modification, changes in lifestyle, and mandibular advancement devices. There are currently no pharmacological options approved for the standard treatment of OSA. There are, however, some pharmacological treatments for daytime sleepiness caused by OSA. Identifying and treating obstructive sleep apnea early is important to reduce the risks of future complications.

Obstructive Sleep Apnea in Adults: What Primary Care Physicians Need to Know.

Obstructive sleep apnea (OSA) remains a prominent disease state characterized as the recurrent collapse of the upper airway while sleeping and is estimated to plague 936 million adults globally. Although the initial clinical presentation of OSA appears harmless, it increases the risk of cardiovascular diseases such as heart failure, stroke, and hypertension; metabolic disorders; and an overall decrease in quality of life, in addition to increasing mortality. Current treatment of OSA includes lifestyle changes, behavioral modification, mandibular advancement devices, surgical treatment, and continuous positive airway pressure, which remains the gold standard. It is crucial to identify OSA early on and initiate treatment to mitigate the adverse health risks it imposes. This review will discuss the pathophysiology, epidemiology, management strategies, and medical treatment of OSA.

Role of Clinical Pharmacists in Intensive Care Units.

The cost of health care has been rising in the United States and globally and will continue to increase. Intensive care unit (ICU) care carries a significant portion of the cost for the hospitals. The Institute of Medicine and subsequent studies have suggested that medication errors account for significant morbidity, mortality, and cost, frequently encountered in the ICU. Over the past three decades, clinical pharmacists have emerged from dispensing medication to getting involved in direct patient care and have become an integral part of the multidisciplinary critical care team. Clinical pharmacists play a significant role in reducing medication errors and costs, medication reconciliation, antibiotic stewardship, and patient and health care provider education. This review will discuss the health care and ICU cost, the evolving role of clinical pharmacists in managing critically ill patients, and their contributions in the ICU to mitigate the risks, improve patient outcomes, and decrease health care costs.

Hepatotoxicity Secondary to Levofloxacin Use.

Levofloxacin is a broad-spectrum antibiotic that is used in the treatment of many infections. A rare adverse drug reaction following the use of levofloxacin is drug-induced liver injury. The exact mechanism behind fluoroquinolone-induced liver injury is unknown, but many severe, sometimes fatal hepatotoxicity cases are reported. Current recommendations advise clinicians to discontinue levofloxacin immediately if the patient develops signs and symptoms of hepatitis. This case report presents a 79-year-old male who was prescribed levofloxacin 500 mg by mouth daily for seven days. The patient had a past medical history of dementia, seizures, cerebral vascular accident, pulmonary fibrosis, and chronic kidney disease. Upon admission, the patient began to show signs and symptoms of liver injury. We hereby present a case report and a review of significant literature on levofloxacin-induced liver injury.

Implementation of Pharmacogenomics and Artificial Intelligence Tools for Chronic Disease Management in Primary Care Setting.

Chronic disease management often requires use of multiple drug regimens that lead to polypharmacy challenges and suboptimal utilization of healthcare services. While the rising costs and healthcare utilization associated with polypharmacy and drug interactions have been well documented, effective tools to address these challenges remain elusive. Emerging evidence that proactive medication management, combined with pharmacogenomic testing, can lead to improved health outcomes and reduced cost burdens may help to address such gaps. In this report, we describe informatic and bioanalytic methodologies that integrate weak signals in symptoms and chief complaints with pharmacogenomic analysis of ~90 single nucleotide polymorphic variants, CYP2D6 copy number, and clinical pharmacokinetic profiles to monitor drug-gene pairs and drug-drug interactions for medications with significant pharmacogenomic profiles. The utility of the approach was validated in a virtual patient case showing detection of significant drug-gene and drug-drug interactions of clinical significance. This effort is being used to establish proof-of-concept for the creation of a regional database to track clinical outcomes in patients enrolled in a bioanalytically-informed medication management program. Our integrated informatic and bioanalytic platform can provide facile clinical decision support to inform and augment medication management in the primary care setting.

Drug-induced liver injury and prospect of cytokine based therapy; A focus on IL-2 based therapies.

Drug-induced liver injury (DILI) is one of the most frequent sources of liver failure and the leading cause of liver transplant. Common non-prescription medications such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and other prescription drugs when taken at more than the recommended doses may lead to DILI. The severity of DILI is affected by factors such as age, ethnicity, race, gender, nutritional status, on-going liver diseases, renal function, pregnancy, alcohol consumption, and drug-drug interactions. Characteristics of DILI-associated inflammation include apoptosis and necrosis of hepatocytes and hepatic infiltration of pro-inflammatory immune cells. If untreated or if the inflammation continues, DILI and associated hepatic inflammation may lead to development of hepatocarcinoma. The therapeutic approach for DILI-associated hepatic inflammation depends on whether the inflammation is acute or chronic. Discontinuing the causative medication, vaccination, and special dietary supplementation are some of the conventional approaches to treat DILI. In this review, we discuss a concise overview of DILI-associated liver complications, and current therapeutic options with special emphasis on biologics including the scope of cytokine therapy in hepatic repair and resolution of inflammation caused by over- the-counter (OTC) or prescription drugs.

Review of Medical Therapies for the Management of Pulmonary Embolism.

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.

Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management.

Heart failure (HF) is a major public health problem in the United States as well as worldwide. Chronic heart failure is a syndrome of reduced cardiac output resulting from impaired ventricular function, impaired filling, or a combination of both. Associated symptoms include dyspnea, fatigue, and decreased exercise tolerance. HF has a marked effect on morbidity and mortality, given limited therapeutic choices. The first line of therapeutic agents indicated in heart failure are beta-blockers. Other drugs and therapeutic modalities employed in HF treatment include angiotensin-receptor blockers (ARBs), sacubitril (neprilysin inhibitor) combination with the ARB, valsartan, small doses of aldosterone receptor antagonists (ARAs) in the setting of angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers. Additionally, the sodium-glucose transporter-2 inhibitor, dapagliflozin in the setting of ACE inhibitors, ARBs, or sacubitril-valsartan plus beta-blocker have been employed. Other therapeutic modalities have included loop diuretics, digoxin, the hydralazine-isosorbide dinitrate combination, ivabradine, the inotropes, dobutamine, milrinone, and dopamine. Decreased cardiac contractility is central to the systolic HF. Therapeutic agents employed to increase cardiac contractility in HF are limited because of their mechanistic-related adverse effect profiles. Omecamtiv mecarbil (OM) is a first of its class cardiac myosin activator that increases the cardiac contractility by specifically binding to the catalytic S1 domain of cardiac myosin, to be employed in heart failure treatment. This agent has demonstrated benefit in reducing heart rate, peripheral vascular resistance, mean left arterial pressure, and left ventricular end-diastolic pressure in the animal models. Additionally, OM is known to improve systolic wall thickening, stroke volume (SV), and cardiac output (CO). OM increases systolic ejection time (SET), cardiac myocyte fractional shortening without significant increase of LV dP/dtmax, myocardial oxygen consumption, and myocyte intracellular calcium. The benefits of OM have been demonstrated through key trials, as (i) The Acute Treatment with Omecamtiv mecarbil to Increase Contractility in Acute Heart Failure (ATOMIC-AHF), and (ii) The Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF). The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial is ongoing and can help provide further clinical data. OM provides a novel mechanism and therapeutic approach to managing patients with HF. Preclinical and clinical data suggest that OM capability can improve cardiac function, decrease ventricular wall stress, reverse ventricular remodeling, and promote sympathetic withdrawal.

Antimicrobial Therapy for Pneumonia or Fluid Overload?

Patients with evidence of fluid overload or heart failure (HF) without clinical symptoms of pneumonia are often treated with antimicrobial therapy for pneumonia. We conducted a retrospective study to evaluate the use of antimicrobial therapy in critically ill patients with fluid overload or heart failure diagnosed as pneumonia. A retrospective chart review of patients on antimicrobial therapy treated for pneumonia in the intensive care unit was conducted. The study's primary outcome was the number of cases with no evidence of pneumonia, including fluid overload or heart failure, managed with antimicrobial therapy for pneumonia. Patients on antimicrobial therapy for other infections were excluded. Appropriateness of antimicrobial therapy was based on radiographic evidence, clinical data, and presentation. Patient group categories were A (pneumonia) and B (no evidence of pneumonia, fluid overload, and heart failure). Based on the subdivision of patients in Group B, where there was no evidence of pneumonia, we further classified it into two subgroups: heart failure (HF)/fluid overload (Group B1) and no evidence of HF or fluid overload (Group B2). Patients with evidence of pneumonia (Group A) were compared to the group with fluid overload and heart failure (Group B1). A p-value of < 0.05% was considered significant for detecting statistical difference. Post-screening, data on 56 patients were collected for the study and analyzed. Mean body temperature and white blood cell count were 37.6 + 0.6 oC, and 17.4 + 6.88 x103 µL, respectively. Based on radiographic evidence, clinical data, and presentation, 29 (52%) were classified under Group A, while 27 (48%) were classified under Group B. Median brain natriuretic peptide (BNP) for Group A vs. Group B was 514 (IQR: 1077) vs. 758 (2212) pg/mL p=0.14. The median duration of inpatient antimicrobial therapy was 7 (interquartile range [IQR]: 6) vs. 6 (IQR: 4) days, p=0.52, while the median duration of the total (inpatient and discharge prescription) antimicrobial therapy was 11 (IQR: 6) vs. 11 (IQR: 5), p=0.21. Patients with evidence of pneumonia (Group A) were compared to the group with fluid overload and heart failure (Group B1). The median BNP for the two groups was 514 (IQR: 1077) vs. 1040 (2094) pg/mL, p=0.04. Patients with documented echocardiographic evidence of ejection fraction < 55% were 4 vs. 14 for Groups A and B1, respectively. Additionally, the median BNP for Group A vs. Group B2 was 514 (IQR: 1077) vs. 189 (418) pg/mL, p=0.02. These findings demonstrate a 48% inappropriate use of antimicrobial therapy in patients with congestive heart failure (CHF), or fluid congestion misdiagnosed as pneumonia. There was a significant difference in the median BNP observed in patients with pneumonia compared to those with fluid overload and heart failure treated as pneumonia. More cases of patients with elevated BNP and reduced left ventricular ejection fraction (LVEF) were observed in patients with fluid overload or CHF treated as pneumonia than those diagnosed with pneumonia alone. Appropriate interpretation of radiographic evidence, laboratory data, and critical clinical assessment for the use of empiric antimicrobial therapy in this population is warranted.

Hypercoagulation from Concomitant Administration of Tamoxifen and Warfarin.

Tamoxifen causing an increase in the anticoagulation effect of warfarin is suggested to be clinically significant, but cases so far have been largely undocumented. Current recommendations advise clinicians to proceed with caution during concomitant therapy. In the presence of other medications known to interact with warfarin, such as antibiotics, proton pump inhibitors, amiodarone, and azole antifungals, international normalized ratio (INR) elevations can possibly be exacerbated even further. We hereby present a case report and a review of significant literature on the use of tamoxifen and warfarin concurrently.