Legionnaires\u27 Disease, A Rising Occurrence in the United States

Legionella pneumophila, a microscopic bacterium usually responsible for a number of illnesses and fatalities, can eliminate a local population, a region or even a nation. In 1976, L. pneumophila was first discovered due to a number of cases presenting with pneumonia-like symptoms. These cases occurred in an isolated population attending an American Legion convention in Philadelphia, Pennsylvania, therefore lending to the name Legionella. Usually found in aquatic environments such as lakes, streams, cooling towers, air conditioning systems and hot tubs, its ability to thrive in artificial and natural environments makes it an ideal bacterium. L. pneumophila can be transmitted via inhaling aerosols that contain the pathogen. After inhalation, the alveolar macrophages phagocytize the pathogen which then serves as its host Virulence factors such as lipopolysaccharides (LPS), are one way the pathogen causes infection, however it can also utilize heat shock protein and surface antigens. Usually with Legionnaires\u27 disease the physical symptoms consist of high fever, malaise, muscle aches, rigors, confusion, headache and diarrhea which categorizes this pathogen as causing an atypical pneumonia. Since L. pneumophila may be associated with travel-related infections, it is hard to track and isolate travel-associated incident clusters because the symptoms present themselves after returning from travel. In regard to diagnosis, this disease has five available techniques to confirm that the patient is in fact positive for L. pneumophila. Programs such as the Environmental Legionella Isolation Techniques Evaluation Program (ELITE) have been started by the Centers for Disease Control and Prevention (CDC) in order to decrease outbreak incidences. Additionally, the current recommendations for the management of Legionnaires\u27 disease adapted from the CDC have been summarized into a flow chart which may help clinical decisions in the treatment of this disease

Use of Botulinum Toxin in Central Nervous System Disorders

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved to treat many different types of disorders but have found significant use for the treatment of migraines, dystonias and cerebral palsy. Botulinum toxin has proven to be efficacious in prophylactically treating those patients with migraines who have failed other pharmacologic and nonpharmacologic treatments. Botulinum toxin is also FDA approved for the treatment of dystonias; more specifically, all three types of botulinum toxin A and the rimabotulinumtoxin B have FDA approval for the treatment of cervical dystonia. Perhaps the most important use for botulinum toxin is in patients with cerebral palsy. Botulinum toxin is efficacious in patients with upper limb spasticity who are not good surgical candidates. It also proves useful as an adjunct to physiotherapy in these patients. This can help reduce or slow progression in patients with cerebral palsy. Exercise has been shown to be an efficacious treatment in patients with migraines, dystonias and cerebral palsy. Further research is necessary to determine the potential benefits the combination of exercise and botulinum toxin can have in these patients. While the high cost of botulinum toxin might deter some patients, it is a good option for those that have exhausted other options or are not good candidates for surgery

Comparison of Long-Term Oral Anticoagulation Therapies Including Newly Approved Reversal Agent for Dabigatran

Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care professional in order to test their international normalized ratio (INR). Newer anticoagulants, including dabigatran, rivaroxaban and apixaban, do not require frequent INR testing and have a quicker onset of action than warfarin, providing convenience for the patient. However, many health care professionals prefer warfarin because the INR may indicate its efficacy, its dosages can be easily changed and it is typically more affordable. Additionally, dabigatran may be chosen because it is the only one of these drugs that has a reversal agent, which can be utilized in the case of major bleeding or emergent surgery. There are many opportunities for pharmacists to impact patient outcomes in the anticoagulation therapy setting. From clinics to the community pharmacy setting, the pharmacist\u27s role in patient counseling and education is crucial in reducing mortality. Additionally, drug development is a growing market as reversal agents are needed for many of these newer anticoagulation therapies

Ramucirumab: A New Agent for Advanced or Metastatic Gastric Junction Adenocarcinoma

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness in combination with paclitaxel as a second-line treatment option. Notable adverse reactions to ramucirumab are severe hypertension and injection site reactions. Because it is a newer anticancer agent, ramucirumab\u27s full potential may not yet be recognized. Possible future uses of ramucirumab may include the treatment of other forms of cancer or utilization as a first-line agent

Combined Neprilysin and Angiotensin Inhibitor for the Treatment of Heart Failure

Heart failure (HF) is a highly prevalent disease state worldwide that can progress into a disabling condition. It is pertinent to have a treatment regimen that is effective in lowering the number of HF exacerbations and, therefore, hospital readmission rates. A novel medication currently in clinical trials, LCZ696, blocks both neprilysin and angiotensin type I receptors. The overall effects are an inhibition of the breakdown of natriuretic peptides which leads to a decrease in renin and aldosterone release. This, combined with the antagonization of angiotensin type I receptors, leads to a decrease in blood pressure, blood volume and systemic vascular resistance. The PARAMOUNT trial compared the therapeutic effectiveness of LCZ696 to valsartan monotherapy. This study demonstrated that patients taking LCZ696 had better improvements in symptoms and biomarkers. The PARADIGM-HF trial compared LCZ696 to enalapril. LCZ696 showed significant reductions in cardiac death, hospitalizations and HF symptoms over enalapril. Although this new medication looks promising as a future treatment option for HF patients, additional studies should be completed to look at the long-term patient outcomes associated with LCZ696

Development of a conceptual framework to guide description and evaluation of social interventions for people with serious mental health conditions

People with serious mental health conditions face social exclusion and have poorer social outcomes compared to the general population in several areas of life. Social exclusion also negatively impacts mental health. Promising models of support to improve social outcomes for people with serious mental health conditions have been described in the literature and proliferate in practice, but typologies of support are not clearly established and a robust evidence base for effective approaches is lacking in many areas. We conducted a scoping review of relevant literature and consulted with experts in the field to identify models to improve social circumstances across eight life domains, with the aim of developing a conceptual framework to distinguish the main broad approaches to improving the social circumstances of people with serious mental health conditions. We also sought to explore which approaches have been used in models within each life domain. This work was conducted in collaboration with a group of expert stakeholders, including people with lived experience of accessing mental health services. We developed a conceptual framework which distinguishes sources and types of support, allowing description of complex interventions to improve the social circumstances of people with serious mental health problems, and providing a framework to guide future service development and evaluation

Toward a chemical reanalysis in a coupled chemistry-climate model: an evaluation of MOPITT CO assimilation and its impact on tropospheric composition

We examine in detail a 1 year global reanalysis of carbon monoxide (CO) that is based on joint assimilation of conventional meteorological observations and Measurement of Pollution in The Troposphere (MOPITT) multispectral CO retrievals in the Community Earth System Model (CESM). Our focus is to assess the impact to the chemical system when CO distribution is constrained in a coupled full chemistry-climate model like CESM. To do this, we first evaluate the joint reanalysis (MOPITT Reanalysis) against four sets of independent observations and compare its performance against a reanalysis with no MOPITT assimilation (Control Run). We then investigate the CO burden and chemical response with the aid of tagged sectoral CO tracers. We estimate the total tropospheric CO burden in 2002 (from ensemble mean and spread) to be 371 ± 12% Tg for MOPITT Reanalysis and 291 ± 9% Tg for Control Run. Our multispecies analysis of this difference suggests that (a) direct emissions of CO and hydrocarbons are too low in the inventory used in this study and (b) chemical oxidation, transport, and deposition processes are not accurately and consistently represented in the model. Increases in CO led to net reduction of OH and subsequent longer lifetime of CH4 (Control Run: 8.7 years versus MOPITT Reanalysis: 9.3 years). Yet at the same time, this increase led to 5-10% enhancement of Northern Hemisphere O3 and overall photochemical activity via HOx recycling. Such nonlinear effects further complicate the attribution to uncertainties in direct emissions alone. This has implications to chemistry-climate modeling and inversion studies of longer-lived species

Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities