Amy Knehans

Determinants of behavioral and psychological symptoms of dementia: A scoping review of the evidence

BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) are prevalent in people with neurodegenerative diseases. PURPOSE In this scoping review the Kales, Gitlin and Lykestos framework is used to answer the question: What high quality evidence exists for the patient, caregiver and environmental determinants of five specific BPSD: aggression, agitation, apathy, depression and psychosis? METHOD An a priori review protocol was developed; 692 of 6013 articles retrieved in the search were deemed eligible for review. Goughs Weight of Evidence Framework and the Cochrane Collaborations tool for assessing risk of bias were used. The findings from 56 high quality/low bias articles are summarized. DISCUSSION Each symptom had its own set of determinants, but many were common across several symptoms: neurodegeneration, type of dementia, severity of cognitive impairments, and declining functional abilities, and to a lesser extent, caregiver burden and communication. CONCLUSION Research and policy implications are relevant to the National Plan to Address Alzheimers Disease.

Olfactory dysfunction in Multiple Sclerosis: A scoping review of the literature

OBJECTIVE Olfactory dysfunction in Multiple Sclerosis (MS) has been reported, but results have been inconsistent. In this review we describe, synthesize, and interpret the existing literature on olfactory dysfunction in Multiple Sclerosis and identify gaps in the current level of knowledge. METHODS The study design was a scoping review of the literature covering several study designs. Systematic Searches of the PubMed, CINAHL, Cochrane Library, Web of Science, PsycARTICLES, PsycINFO and Google Scholar databases were conducted that included key words related to Multiple Sclerosis and Olfaction Disorders. Literature that met the criteria of pertaining to both Multiple Sclerosis and olfactory dysfunction was identified, with the aim of providing an overview of the extent and types of research available in this area. RESULTS Sixty-one reports were identified in the initial search, with 40 meeting the study criteria. Twenty-five clinical studies were included. Among them, 23 studies measured for olfactory dysfunction in MS patients, ten evaluated MRI correlates of olfactory dysfunction, and five evaluated neurophysiology correlates of olfactory dysfunction. Six of the included studies were abstracts. In addition, thirteen reviews/commentaries and two case studies were included. The majority of the studies identified some degree of olfactory dysfunction in MS patients, and various aspects and correlations with olfactory impairment were observed. CONCLUSIONS The overall weight of the literature suggests that olfactory dysfunction may occur in MS. Although there is variability in reported frequency, the more robust studies suggest the prevalence is significant, ranging from 20% to 45% in the MS population. Despite this, the mechanisms are unknown and the clinical relevance of this association has not been well explored. Interesting findings relating mood disorders, cognition, and olfactory dysfunction in MS are also suggested but remain poorly developed and require further investigation. Future studies are also warranted to understand the dynamic changes in olfactory function during the course of MS, and to correlate olfactory function with relapses/disease activity.

Implementing and Sustaining Evidence Based Practice Through a Nursing Journal Club.

BACKGROUND The outcomes based emphasis in nursing and health care delivery requires identification of best available evidence in order to produce quality, safe, and effective patient care. Finding, critiquing, and ultimately implementing the best available evidence for practice is a formidable task for many clinical nurses. Development and implementation of a nursing journal club (NJC) became one organizations successful attempt to help clinical nurses better understand and use best available evidence in actual practice. METHODS The process and structure for the NJC evolved from an additional activity scheduled outside of work to a fully established endeavor of Nursing Research and Evidence Based Practice Council (NR&EBP). The Nursing Professional Practice Model was foundational to establishing the NJC as a formal component within the NR&EBP Council shared governance structure. Efforts to embed the NJC included taking advantage of resources available at an academic medical center and incorporating them into the council structure. RESULTS Successful outcomes of the NJC include a quarterly schedule, with topics selected in advance that are based on nursing department as well as organizational driven goals and initiatives. The structure and process in place has eliminated frequently mentioned deterrents to evidence based practice such as not enough time, lack of knowledge, or no immediate application to practice. CONCLUSIONS Incorporating the NJC as a component of NR&EBP Council has provided clinical nurses time away from clinical care that supports scholarship for nursing practice. Committed leadership and garnering of available resources have been key factors for success.

The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review

Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM) is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

Individualized Patient-Centered Care: A Physician Assistant Curriculum in Information Mastery, Clinical Reasoning, and Shared Decision Making

This article describes a novel preclinical physician assistant (PA) curriculum that teaches skills in point-of-care information mastery, patient-centered communication, clinical reasoning, and the process of shared decision making—all leading to a truly individualized patient-centered care model. In the 1990s, Sackett described evidence-based medicine (EBM) as the conscientious, explicit, and judicious use of the best current evidence in making decisions about the care of individual patients. In 2002, Guyatt et al stated the principle that evidence is never enough: patient values and preferences must also be considered. Using EBM to develop an appropriate plan of care for an individual patient, therefore, means integrating clinical expertise with the best available external clinical evidence andwith thepatient’s values inmind. Shared decisionmaking is the process bywhich thebest evidence and individual patient preferences are considered and acted upon by the health care provider and the patient as partners. EBM and shared decision making are both essential for patientcentered care. Practicing these principles is crucial because an estimated average of 3.2 clinical questions arise for every 10 patient encounters in primary care, yet only one-third of these questions are answeredor pursued.AlthoughMEDLINEpublishes over 2000 articles daily, health professionals spend an averageof just 2minutes to search for information. Toaddress this problem, Slawson and Shaughnessy incorporate the best evidence into the busyworld of clinical practice by focusing on finding, evaluating, and using information at the point of care. They use the term “information mastery” for this process and note that it requires sources that have critically appraised and graded thequality of the evidence. Extensive application of sophisticated statistical skills and the time to perform them can now be delegated to evaluation services such as the United States Preventative Services Task Force (USPSTF) or a validated database such as DynaMed. By contrast, traditional EBMeducation inmedical school and PA curricula often focuses on statistical analysis and critical appraisal of articles. Information mastery, point-of-care use, and shared decision making are not typically part of this traditional curriculum and are inadequately described in the PA literature. Goldgar and Keahey describe their experience of connecting the curriculum to patient care using the EBMwrite-up method that requires learners to apply concepts of EBM to a clinical question arising from a patient encounter. These same authors describe the best clinical information tools according to the individual student’s stage of training. Werner and Richter highlight educational instruction of reliability concepts in EBM appraisal and how this type of training prepares PAs to communicate scientific results with other clinicians. Physician assistant training continues to be anchored by the fundamental concepts of anatomy and pathophysiology, physical diagnosis, and principles of pharmacology. Our curriculum teaches the foundational concepts of EBM and information mastery in one course and patient-centered communication skills, clinical reasoning, and shared decision making in a second and parallel course, comprising the pillars of our model for teaching individualized patientcentered care (Figure 1). The focus of this article is the design and outcome of that model. The curriculum allows PA students, while they study EBM and information management, to learn and practice entering into a dialoguewith thepatient, guiding thepatient to choices and leading the patient to take ownership of disease management through incorporating individual patient preferences. Consequently, our goal is to provide PA students with the skillset needed to engage patients in shared decision Feature Editor’s Note:

Starting a Fee-Based Systematic Review Service

ABSTRACT The George T. Harrell Health Sciences Library at Penn State College of Medicine began a fee-based systematic review service, a model for cost recovery, in October 2013. This article describes the library’s experience in establishing, introducing, and promoting the new service, which follows the Institute of Medicine’s recommended standards for performing systematic reviews. The goal is to share this information with librarians who are contemplating starting such a service.

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of endometrial cancer: a scoping review of the current literature

Objective: To describe, synthesize, and interpret literature on the role of poly (ADP-ribose) polyermase inhibitors in the treatment of endometrial cancer and to identify areas of interest for future reasearch. Design: Scoping review of the literature covering several study designs. Setting: Literature review. Methods: Systematic Searches of the electronic databases PubMed® (MEDLINE®), Cochrane Library®, CINAHL®, and Web of ScienceTM were performed, as well as web-based searches (ClinicalTrials.gov, Canadian Clinical Trials & Cancer Trials, Australian Clinical Trials, WHO ICTRP, NIH Reporter, the CDC, and Google Scholar) for additional material, such as reports commissioned by government as well as non-governmental agencies. Literature was identified and organized into categories then synthesized to form conclusions and identify knowledge gaps. Results: 96 records were identified after searching the literature and 69 records were subsequently reviewed. Conclusion: There is conflicting evidence regarding the utility of proposed biomarkers in predicting sensitivity of endometrial cancer to PARP inhibitor treatment. Current in vitro and in vivo studies suggest that PARP inhibitors may be effective in the treatment of certain subsets of endometrial cancer, but further research is warranted. Correspondence to: Joshua P. Kesterson, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17036, Tel: (717) 531-8144 (ext. 5); Fax: (717) 531-0007; E-mail: jkesterson@hmc.psu.edu Received: April 28, 2016; Accepted: May 30, 2016; Published: June 03, 2016 Introduction Endometrial cancer is the most common gynecologic cancer in the United States [1]. While early-stage cancer is generally cured with surgery, the therapeutic options for advanced and recurrent endometrial cancer are limited, with minimal efficacy, short-lived responses and significant toxicity [2-4]. In fact, the most effective regimens result in an overall survival of 12-15 months [5,6]. These results highlight the need for novel agents, including a shift toward targeting specific molecular and genetic pathways involved in endometrial carcinogenesis. One such target is Poly (ADP-ribose) polymerase, or PARP. PARP is a family of 17 enzymes that catalyze the polyADPribosylation of proteins involved in the repair of single stranded DNA breaks via the base excision repair (BER) pathway [7,8]. PARP1 is activated in response to metabolic, chemical, or radiation-induced breaks in the DNA strand. Once a single stranded break is detected, PARP1 recruits and activates enzymes needed to repair the damaged strand via the transfer of ADP-ribose molecules from NAD+ to itself and other DNA repair proteins [7,9]. In addition to its role in the repair of single strand break (SSB) DNA, PARP aids in the prevention of formation of double strand breaks (DSB) in DNA via its recognition of stalled replication forks and recruitment of MRE11, which initiates the homologous recombination (HR) pathway [10]. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) inhibit PARP function by two major mechanisms. First, they compete with NAD+ for access to the substrate binding site [11] and secondly, they trap PARP1 and PARP2 while complexed with DNA leading to cell death due to blocked DNA repair ability [12]. PARP inhibitors therefore lead to persistence of single stranded breaks in DNA due to impaired BER [9]. If unrepaired, these single stranded breaks lead to replication fork collapse or the generation of double-stranded breaks in DNA. Cells with intact homologous recombination (HR) DNA repair mechanisms are able to repair the double stranded breaks and the cells remain viable. However, in the absence of intact HR, cells are unable to repair double-stranded breaks and subsequently undergo apoptosis [13-15]. This exemplifies the concept of synthetic lethality, in which two specific defects, neither of which are overtly detrimental to the cell individually, but lethal when they occur together. The synthetic lethality of PARP inhibitor treatment in tumor cells Ricci S (2016) The role of poly(ADP-ribose) polymerase inhibitors in the treatment of endometrial cancer: a scoping review of the current literature Volume 1(1): 10-15 Clin Med Invest, 2016 doi: 10.15761/CMI.1000102 with defects in HR repair, including BRCA-mutated ovarian cancers has been demonstrated [16-19]. Clinical trials of monotherapy with the oral PARP inhibitor olaparib have shown objective antitumor activity in ovarian cancer [17-19]. Additional studies have focused on the efficacy of other PARP inhibitors in BRCA mutation carriers [20] and BRCA-mutated cancer cells [21]. Similarly, PARP inhibitors may have increased efficacy in tumors which exhibit “BRCAness”; that is, tumor cells deficient in HR but without a known or detectable BRCA1 or BRCA2 mutation [22]. Mutations in phosphatase and tensin homolog (PTEN) and MRE11 may cause tumor cells to exhibit a “BRCAness” phenotype, due to their role in DNA repair. PTEN is a tumor suppressor gene located on chromosome 10q23.3 that functions as an antagonist of the prosurvival/proliferative PI3K/AKT pathway [23]. In addition to its role in regulating the cell cycle, PTEN is also involved in DNA double-stranded break repair via upregulation of the gene encoding RAD51, a protein involved in DNA repair [23]. A diverse group of mutations in PTEN can lead to the generation of solid tumors; in fact, PTEN mutations are the most common molecular defect in endometrioid endometrial adenocarcinoma [24,25], seen in up to 83% of these endometrial cancers [24-27]. MRE11 is a protein that, together with RAD51 and NBS1, forms a complex involved in the detection and repair of DSBs in DNA [28,29]. The prevalence of MRE11 mutations in endometrial cancer is the subject of investigation, with studies suggesting mutation frequencies ranging from 1.9% to 50% [30,31]. Given the frequency of these mutations in endometrial and the implications of impaired DNA repair, it is plausible that endometrial cancers carrying these mutations have inadequate HR and therefore may be sensitive to PARP inhibitors. The purpose of this review is to analyze the current literature regarding the role of PARP inhibitors in the treatment of endometrial cancer, summarize results of available data, and identify areas warranting further research.

Partnering to Promote Evidence-Based Practice by Implementing Nursing Reference Center at the Point of Care

Nurses need easy access to authoritative resources for decision-making and development of nursing interventions at the point of care. Perceived lack of time, limited awareness of resources, and training opportunities are obstacles to accessing evidence-based resources at the bedside. A medical librarian and the nursing shared governance council for Nursing Research & Evidence Based Practice partnered to enhance education and training for nurses in evidence-based practice. Nursing Reference Center became one of the tools to accomplish the goal. This paper presents one organization’s attempt to overcome obstacles to evidence-based practice that clinical nurses encounter, namely, access to best available evidence at the patient’s bedside.

Worldwide need for a comprehensive database of stability data for pharmaceuticals stored in uncontrolled environments.

Developing a database to compile all known, relevant information on the stability of pharmaceuticals in tropical environments would vastly increase access to this information, improving safety and reducing cost. Many studies have examined the stability of pharmaceuticals stored under conditions that exceed manufacturer specifications, but this information is published across so many journals and Websites that it can be virtually inaccessible to clinics or suppliers needing to make pharmaceutical inventory management decisions. We have made progress toward the completion of a database of this nature, but resources and abilities of international public health organizations will be needed to bring the database fully to fruition.