Current Utilization of Antifungal Agents for Intra-abdominal Infections Categorized by Patient Risk Factors During Surgical Procedures: A Literature Review.

The high morbidity and mortality rates associated with invasive fungal infections have led to the overutilization of empiric antifungal therapies. With increasing antibiotic resistance, the careful consideration of prophylactic or empiric antifungal use is critical. The purpose of this review is to evaluate the available literature regarding the current practice of utilizing antifungal agents for intra-abdominal infections based on specific surgical procedures and patient risk factors. Relevant articles were identified through a comprehensive literature search of several databases using the keywords antifungal agents, postoperative period, preoperative care, surgical procedures, and intra-abdominal infections. Only articles that evaluated the use of empiric antifungals for suspected or confirmed intra-abdominal infections and surgical procedures were included in this review. Based on the available literature, antifungal prophylaxis is appropriate in patients who meet the criteria for high-risk invasive candidiasis, kidney or liver transplant recipients, severely-immunocompromised patients with perforated peptic ulcer, peritonitis, and patients on peritoneal dialysis who are failing on a therapeutic antibiotic regimen. We acknowledge that the evidence for using antifungal therapy empirically for all surgical procedures is lacking, and the following review is based on available literature and current guidelines.

The Use of Neuromuscular Blockers to Prevent Shivering in the Setting of Postcardiac Arrest Targeted Temperature Management: A Narrative Review of an Off-Label Indication.

Targeted temperature management (TTM) has become a standard of care over the past two decades for the improvement in neurologic function and mortality in postcardiac arrest patients. There are various mechanisms by which hypothermia helps to improve these outcomes, one of which is by reducing oxygen requirements. Less established is the use of nondepolarizing neuromuscular blockers (NMBs) to prevent shivering during TTM. Shivering can be disadvantageous in this setting as it increases oxygen requirements, which TTM is actively trying to decrease, in an already oxygen-deprived system as well as generates heat making it difficult to maintain hypothermia. Whether NMBs can improve these outcomes is conflicting in the currently available literature and there lacks a consensus on their role in shivering management. The pharmacokinetic and pharmacodynamic responses of these agents may be altered in hypothermic patients, therefore, their standard of monitoring may be unreliable. The accurate dosing and administration of these agents also remain unclear, further complicated by the lack of a standard use protocol. Various studies have been conducted regarding the use of NMBs to prevent shivering in postcardiac arrest patients undergoing TTM; however, it remains an off-label indication requiring further investigation.

Combined oral contraceptive use in rheumatoid arthritis for the purpose of pregnancy prevention and additional benefits: A narrative review.

Combined oral contraceptives are a common method of contraception and many females prefer them regardless of their medical history. The use in patients with rheumatoid and autoimmune disorders has not been extensively studied with previous reviews focusing on the safety component. This review seeks to address the effectiveness and benefits of utilizing combined oral contraceptives in females with rheumatoid arthritis (RA). Current literature regarding combined oral contraceptives was surveyed for its use in RA and two PubMed searches were conducted, yielding 202 and 142 results, respectively. Results were screened and analyzed for relevance to this review topic. Eighteen results, consisting of clinical trials, observational studies, patient cases, and meta-analyses were used in this narrative review. Historically, it was thought that females with an autoimmune disorder such as RA need to be on contraception due to the teratogenicity potential with disease-modifying therapy but no evidence exists about which type of contraception is the most effective and least interacting. Current evidence available shows no preference for types of contraception in this population, but it has been demonstrated that combination oral contraceptives may provide contraceptive benefits and have a potential for other benefits such as less disability and the prevention of disease progression. Although current evidence provides reasoning to believe combination oral contraceptives are safe and efficacious in patients with RA and may even offer additional benefits, further studies and clinical trials are needed to completely understand the role combination oral contraceptives play in this patient population.

The use of aloe vera in cancer radiation: An updated comprehensive review.

INTRODUCTION: Many cancer patients require radiation therapy and often experience adverse effects including erythema, itching, and pain. Aloe vera has been studied for its potential use in the prevention and treatment of radiation related adverse effects as it possesses a variety of properties and is considered an antioxidant and anti-inflammatory agent. Multiple controlled trials have been performed in order to evaluate the efficacy of aloe vera for the prevention and treatment of radiation side effects. Previous systematic reviews have examined the use of aloe vera for radiation-induced skin reactions, however updated literature now includes the use of aloe vera in proctitis. OBJECTIVES: The aim of this comprehensive review is to summarize and evaluate the use of aloe vera in patients who have undergone radiation therapy for the treatment of cancer. RESULTS: Aloe vera may not be effective for prophylaxis or treatment of radiation adverse effects in breast cancer patients. Moderate efficacy was seen when aloe vera was used in combination with mild soap versus soap as monotherapy for the treatment of radiation skin reactions. Aloe vera may be effective when cumulative radiation doses are greater than 2,700 cGy and for acute radiation proctitis. CONCLUSIONS: There is contradictory evidence for the use of aloe vera in the setting of radiation in regards to its efficacy in the prevention and treatment of radiation-induced adverse effects.

Pegvaliase: a novel treatment option for adults with phenylketonuria.

OBJECTIVE: In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase. METHODS: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Additional information was gathered from the pegvaliase package insert, posters presented at scientific meetings, and materials provided from the manufacturer, BioMarin. RESULTS: Pegvaliase is effective in decreasing blood phenylalanine levels, and is associated with a manageable side-effect profile. Phase III clinical trial data demonstrated that 60.7% of patients were able to achieve blood phenylalanine levels less than the guideline recommended 360 µmol/L at 24 months. Brief sub-studies also showed the improvement in inattention symptoms in patients treated with pegvaliase, compared to placebo. CONCLUSION: Pegvaliase is a promising new treatment option for adults living with PKU. Further studies are warranted to determine long-term safety and clinical efficacy in sub-populations.

Herpes zoster subunit vaccine for the prevention of herpes zoster.

PURPOSE: Published literature on the efficacy and safety of the herpes zoster (HZ) subunit vaccine (HZ/su vaccine) in reducing the risks of HZ and postherpetic neuralgia (PHN) in adults 50 years of age and older, as well as the vaccine's properties and efficacy relative to live attenuated vaccine, is reviewed. SUMMARY: HZ/su vaccine (Shingrix, GlaxoSmithKline) is a recently Food and Drug Administration (FDA)-approved vaccine indicated for the prevention of HZ in adults 50 years of age and older. Based on several Phase III trials, the Advisory Committee on Immunization Practices has preferentially recommended HZ/su vaccine over a live attenuated vaccine previously approved by FDA. Reported overall HZ/su vaccine efficacy in preventing HZ in Phase III trials ranged from 89.8% to 97.2%. Compared with placebo use, HZ/su vaccine in those trials was associated with higher rates of transient local and systemic adverse events (AEs) but similar rates of serious vaccine-related AEs. Other clinical trials of HZ/su vaccine have yielded favorable results in various populations, including adults with a history of HZ, older adults who previously received live attenuated zoster vaccine, adults with human immunodeficiency virus infection, and stem cell transplant recipients. CONCLUSION: HZ/su vaccine is a recently approved, preferred option to reduce the risks of HZ and PHN in adults 50 years of age or older. Pain at the injection site is the most common AE associated with use of the vaccine.

Solithromycin (CEM-101): A New Fluoroketolide Antibiotic and Its Role in the Treatment of Gonorrhea.

Solithromycin is a macrolide antibiotic that has undergone review for the treatment of community-acquired bacterial pneumonia. Solithromycin is also being investigated and has shown promise for the treatment of gonorrhea. With increasing antibiotic resistance, the development of novel antibiotics to combat infections is essential. The unique ribosome-binding stability of solithromycin and mild side effect profile make this a promising new antibiotic. This article will provide an overview on the mechanism of action, clinical efficacy, and safety of this drug for the treatment of gonorrhea. Relevant data were identified through a comprehensive literature search using multiple databases using the keywords solithromycin, CEM-101, and gonorrhea.

Comparing methods of naloxone administration: A narrative review.

The effectiveness and safety of naloxone for the reversal of opioid toxicity are reviewed. A literature search was performed using PubMed, the Cochrane Library, CINAHL, and Medline. Clinical trials comparing either the clinical efficacy or pharmacokinetic/pharmacodynamic properties displayed by intravenous, intramuscular, intranasal, subcutaneous, and nebulized naloxone were included; however, trials with primary endpoints evaluating oral or endotracheal naloxone were excluded. Naloxone was shown to be clinically effective via all routes of administration, when compared to either baseline or control. The inconsistencies in data regarding the relative outcome comparisons between administration methods were likely due to differences in concentrations of naloxone preparations and method of administration for the same route of delivery between different studies. Choice of route depends on the environment in which the opioid toxicity occurs, individual patient characteristics, and provider preference.

Clinical efficacy of turmeric use in gingivitis: A comprehensive review.

INTRODUCTION: Gingivitis affects an estimated 80% of the population, and is characterized as the world's most predominant inflammatory periodontal disease. Without intervention, gingivitis can advance to alveolar bone loss. Therefore, the primary goal in patients suffering with gingivitis is to control plaque buildup and soft tissue inflammation. Current guidelines consider chlorhexidine as the gold standard in the prevention and treatment of gingivitis. However, negative side effects of chlorhexidine, including oral mucosal erosion, discoloration of teeth, and bitter taste, provide an opportunity for alternative medications. Turmeric, a commonly used herb, possesses anti-inflammatory, antioxidant, antibacterial, antiviral, and antifungal properties. By virtue of these properties, multiple controlled trials have been performed to investigate the efficacy of turmeric in gingivitis. OBJECTIVES: The aim of this comprehensive review is to summarize and evaluate the evidence on the efficacy of turmeric as compared to chlorhexidine in the prevention and treatment of gingivitis. RESULTS: PubMed, MedLine (Web of Science), and EBSCO (academic search complete) were utilized as primary literature search tools. The following search strategy was used: ((turmeric OR curcumin OR curcuma) AND (gingivitis OR "gum inflammation")). Five reviewed studies show that both turmeric and chlorhexidine significantly decrease plaque index (PI) and gingival index (GI), and can therefore be used in the prevention and treatment of gingivitis. CONCLUSIONS: Both chlorhexidine and turmeric can be used as an adjunct to mechanical means in preventing and treating gingivitis. However, trials longer than 21 days with a greater number of patients are necessary to further evaluate the comparison between turmeric and chlorhexidine.

Patiromer: a clinical review.

IMPORTANCE: Patiromer FOS (for oral suspension), formerly known as RLY5016, is pending FDA approval for the treatment of hyperkalemia. Once approved, patiromer, as well as a second agent known as sodium zirconium cyclosilicate (ZS-9), will be among the new therapeutic options available to treat hyperkalemia in over 50 years. OBJECTIVE: The primary objective of this review is to analyze the efficacy and safety of patiromer to treat hyperkalemia and compare its pharmacokinetics to currently available sodium polystyrene sulfonate (SPS) therapy. Patiromer was studied in patients with chronic kidney disease and/or heart failure for both acute and chronic therapy. EVIDENCE REVIEW: Studies of patiromer were obtained via a literature search of PubMed database and Google Scholar (2000 to the present) using 'patiromer', 'RLY5016', and 'hyperkalemia management' as keywords. Additional references were identified from fda.gov, clinicaltrials.gov, and the pharmaceutical manufacturer, Relypsa Inc. FINDINGS: Three published clinical trials, ten posters, one clinical trial commentary, three editorials and one oral presentation were obtained. The materials discussed three main clinical trials (PEARL-HF, OPAL-HK and AMETHYST-DN) and examined the safety and efficacy of patiromer in patients with hyperkalemia or at risk for hyperkalemia who have chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), hypertension and/or heart failure (HF) while receiving renin-angiotensin-aldosterone system inhibitors (RAASis). All three studies achieved their primary endpoints and reduced serum potassium. The PEARL-HF study increased the proportion of patients able to titrate their spironolactone dose from 25 mg/day to 50 mg/day in patients with normokalemia who had a history of hyperkalemia or an estimated glomerular filtration rate of <60 mL/min. The OPAL-HK study allowed patients receiving patiromer to remain on their RAASi therapy. The AMETHYST-DN study demonstrated that patiromer reduced and maintained mean serum potassium ≤5.0 mEq/L for up to 1 year, with a low rate of hypokalemia. Adverse events (AEs) were similar between studies. The most commonly reported adverse event was constipation. CONCLUSIONS AND RELEVANCE: Patiromer is effective in decreasing serum potassium, preventing recurrence of hyperkalemia, and reducing RAASi discontinuation. Compared to current SPS therapy, patiromer may be the preferred option to treat hyperkalemia, once approved. Patiromer is well tolerated and is not associated with serious AEs.

Drug-Drug Interactions Among Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Medications.

One-fourth of individuals diagnosed with the human immunodeficiency virus concomitantly have the hepatitis C virus infection. Since the discovery of highly active antiretroviral therapy, liver complications have become the leading cause of morbidity and mortality in HIV-HCV coinfected individuals. Optimal treatment in this patient population is critical, as coinfection has been linked to deterioration of both disease states. The objective of this review article is to highlight the current literature on drug-drug interactions between HIV and HCV treatments. The management of the treatment of coinfection patients has been covered extensively in numerous other publications.

Safety of Popular Herbal Supplements in Lactating Women.

The increasing popularity and use of dietary supplements has required health care professionals to become more knowledgeable of their properties, interactions, and adverse effects. The objectives of this review were to evaluate the safety of popular dietary supplements in breastfeeding mothers and the effects on the infants. Nine of the most popular herbal dietary supplements were identified based on the 2011 US market report of the top 10 selling botanicals and the most frequently received inquiries by the Ruth A. Lawrence Lactation Study Center at the University of Rochester Medical Center. Relevant publications were identified through June 2014 using PubMed and EMBASE; tertiary references, including the Drugs and Lactation Database and Natural Medicine Comprehensive Database, were also reviewed. These herbals include black cohosh, cranberry, echinacea, evening primrose, garlic, ginseng, melatonin, milk thistle, and St John's wort. Studies varied greatly with regard to study design, herbal intervention, and outcome measures. Findings suggested that dietary/herbal supplements have not been evaluated in high-quality clinical trials, and there is limited evidence supporting safety of use, particularly among lactating women. Therefore, it is essential for physicians to provide counseling for nursing mothers seeking information on dietary supplements, highlighting reliable safety profiles, inquiring about the potential benefits the patient is seeking, and assessing the patient's perception of this supplement during breastfeeding. More research and clinical trials are required in this area to guide the recommendations and expand our current knowledge of these products.

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder.

In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings.

Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder.

In July 2013, the US Food and Drug Administration approved levomilnacipran extended release (ER; Fetzima), a serotonin-norepinephrine reuptake inhibitor, for the treatment of adults with major depressive disorder. Levomilnacipran is an active enantiomer of the racemic drug milnacipran that is currently approved in the United States for the treatment of fibromyalgia. This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, safety, and tolerability of levomilnacipran ER. Relevant information was identified through a search of databases using the key word levomilnacipran. Additional information was obtained from fda.gov, by a review of the reference lists of identified articles, and from posters and abstracts from scientific meetings. Levomilnacipran ER, dosed once daily, is generally well tolerated and has demonstrated favorable effects compared to placebo in clinical trials of patients with major depressive disorder. The increased potency for norepinephrine reuptake inhibition is a characteristic that may represent a novel contribution for levomilnacipran. Additional studies comparing levomilnacipran ER to other commonly prescribed antidepressants are needed to further evaluate its place in therapy.

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis.

OBJECTIVE: To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS). DATA SOURCES: A comprehensive PubMed search was conducted in July 2013 using the search terms dimethyl fumarate and Tecfidera. Reference lists of abstracted publications were reviewed to identify relevant works that were not retrieved via the electronic search. Additional information was obtained from the FDA Web site, manufacturer prescribing information, and Clinicaltrials.gov. STUDY SELECTION AND DATA ABSTRACTION: Clinical trials and review articles that included the use of dimethyl fumarate in the treatment of MS and were available in English were abstracted for review. DATA SYNTHESIS: The safety and efficacy of dimethyl fumarate for the treatment of relapsing remitting MS was confirmed in 2 phase III trials, DEFINE and CONFIRM. Relative to placebo, twice-daily dimethyl fumarate was found to reduce the proportion of patients with relapses at 2 years by 34% to 49% and the annualized relapse rate by 44% to 53%. Although the incidence of serious adverse effects did not differ from that of placebo, intolerable flushing and gastrointestinal adverse effects prompted discontinuation in 3% and 4% of patients, respectively. CONCLUSIONS: In March 2013, dimethyl fumarate was approved as a third oral option for patients with relapsing forms of MS. Although no head-to-head trials have been conducted, a comparison of data from phase III trials suggests that the efficacy of dimethyl fumarate is comparable to that of existing oral agents and may offer a preferable safety profile.