Oral Mucositis and Stomatitis Associated with Conventional and Targeted Anticancer Therapy

Oral mucositis and stomatitis are characterized by pain, inflammation, and redness in the oral cavity. In the case of mucositis, ulceration also occurs. Despite being understudied, these symptoms are some of the most troubling, and yet common, adverse effects associated with cancer treatment. The incidence of these toxicities is highly variable depending on treatment-related and patient-related risk factors. However, most cancer treatment regimens carry some risk of this toxicity. The presence of mucositis or stomatitis can result in a significant decrease in the patient?s quality of life due to severe pain and the inability to eat or drink. These toxicities can also negatively affect the overall outcome of cancer treatment, leading to dose reductions and delays in treatment. Although the mechanism is not yet understood, the rapid increase in the number of targeted anticancer therapies available on the market has increased the number of patients who experience oral toxicities. The toxicities caused by targeted agents are less severe than those caused by conventional anticancer agents, but due to prolonged dosing schedules, they can still lead to significant declines in quality of life. The pathobiology of oral mucositis is a complex five phase process. It involves injury, activation of enzymes and transcription factors, upregulation of cytokine genes, inflammation/damage to tissue, and healing. These processes not only involve cells in the oral mucosa, but also the surrounding fibroblasts and connective tissue cells. A better understanding of the mechanisms behind oral mucositis and stomatitis will facilitate the development of effective prediction, prevention, and treatment strategies

Assessment of the Use of Non-Pharmacological Methods for Managing Depression in Patients with Myotonic Dystrophy (DM) and Facioscapulohumeral Muscular Dystrophy (FSHD)

Background: Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are two types of muscular dystrophies with multi-system manifestations. Purpose: The purpose of this study was to determine 1: the prevalence of depression in patients with myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) and 2: which non-pharmacological methods DM and FSHD patients are using to manage their depression. Methods: A survey was conducted using the online system, Qualtrics. The voluntary and anonymous survey was emailed to 1,205 eligible patients from the National Registry for DM and FSHD Patients and Family Members at the University of Rochester. Participants were at least 18 years old, a member of the registry, and diagnosed with DM or FSHD. The 65 question survey included questions on basic demographic information, depression diagnosis, medication use and effectiveness, and non-pharmacological management. Surveys were collected between May 2017 and August 2017 and the responses were analyzed and compared to the general population. The study was approved by the St. John Fisher College Institutional Review Board and the Registry Scientific Advisory Committee. Results: Of the 1,205 surveys that were sent, 466 patients responded. A total of 46 percent of patients had DM (DM1 30 percent, n=138/460 and DM2 16 percent, n=75/460) and 48 percent (n=223/460) of respondents had FSHD. Of the study respondents, 34 percent (n=150/436) reported being diagnosed with depression, while 8 percent (n=24/294) feel depressed, but haven’t been diagnosed. Non-pharmacological techniques used by patients who were diagnosed with depression or feel that they are depressed included: exercise (33 percent, n=57/150), relaxation techniques once per week (51 percent, n=50/98), and visiting a counselor or therapist once per week (11 percent, n=4/37). The most common type of relaxation technique used was meditation (52 percent, n=77/147) followed by yoga (18 percent, n=24/147). In conclusion, 32 percent (n=34/107) stated that relaxation techniques helped them, and 49 percent (n=52/107) stated that relaxation techniques may have helped them. Conclusion: Patients with both DM and FSHD have been diagnosed with depression. To manage their depression, and similar to what occurs in the general population, DM and FSHD patients are using a combination of both pharmacologic and non-pharmacologic strategies. DM and FSHD patients also believe that these non-pharmacologic methods, which include exercise, counseling, and relaxation techniques are helpful in their managing depression

Analyzing Pain Medication Use and Adherence in Patients with Myotonic Dystrophy and Facioscapulohumeral Dystrophy

Objectives: Myotonic dystrophy (DM) and facioscapulohumeral dystrophy (FSHD) are two of the most common muscular dystrophies in adults. It has been reported that patients with these two disorders may suffer from pain and inadequate pain management. The purpose of this study is to analyze the current use of pain medications and develop a survey to assess pain medication use and adherence in this patient population. Methods: Patients registered in the National Registry for DM and FSHD at the University of Rochester were surveyed on pain medication use and the most significant problem of their disease. After analysis of these surveys, an additional survey was created that contained questions specifically on pain medication use, adherence, and general questions about the patients’ pain. Questions for the survey were devised from previous studies on medication adherence, questionnaires on medication adherence and beliefs, and questions from the Brief Pain Inventory. Results: In the first survey, pain medication was used by 34% of the survey respondents (n=519/1527). Specifically, NSAIDs were used by 23.5% and opioids were used by 4% of survey respondents. In a separate survey, pain was reported as the most burdensome problem by 8% of patients (n= 27/355). This was greater than problems related with balance (n=10/355), fatigue (n=20/355), or gastrointestinal distress (n=8/355). Conclusion: Despite the low reported response that pain was the most significant problem associated with their disease, the prevalence of pain medication use indicates that further study into the impact of pain and pain medication use in this patient population is warranted. Specifically, investigating questions about adherence, use, and beliefs toward pain medication will lead to an increased understanding of pain and its treatment in this patient population. This knowledge can lead to the ability of pharmacists to optimize pain management and to reduce adverse reactions to pain medications

Course-Level Curriculum Map Pilot Program

Objective: To pilot a newly developed course level curriculum map that documents course learning outcomes, corresponding teaching activities, assessments, student achievement on assessments, and evidence-based changes made subsequently at the course level. Method: The newly developed course level curriculum map was piloted in twelve courses involving nine faculty members. Faculty either retroactively recorded data or utilized the map during the semester. At the conclusion of the pilot period, a focus group was conducted during which seven of the faculty members shared experiences and recommendations. Focus group comments were recorded by three people. Recorders’ notes were compared for accuracy and completeness. Notes were analyzed using ATLAS.ti, a qualitative research program. Results: Qualitative analysis of focus group notes yielded four principal comment codes: learning outcomes, changing activities, documenting changes, and changing assessments. These four main codes document that faculty believe work is needed on writing better course learning outcomes, creating more appropriately matched course activities, better documenting data-driven changes that occur at the course level, and developing appropriate assessments. Implications: Faculty comments support school-wide adoption of course level curriculum mapping. They also suggest a need to provide faculty development on writing precise learning outcomes and mapping them to specific classroom activities to support outcomes achievement. Additionally, curricular changes made at the course level need to be carefully documented and linked to appropriate evidence derived from assessments. The value of the map for inclusion in the dossier for promotion and tenure was also noted

A Transgender Health Care Panel Discussion in a Required Diversity Course

OBJECTIVES: To examine the impact of a panel discussion on transgender health care on first-year (P1) pharmacy students\u27 knowledge and understanding of transgender experiences in an Introduction to Diversity course. DESIGN: The panel consisted of both transgender males and females. After panelists shared their healthcare experiences, students asked them questions in a moderated setting. Students completed evaluations on the presentation and learning outcomes. They also wrote a self-reflection paper on the experience. ASSESSMENT: Ninety-one percent of students agreed that they could describe methods for showing respect to a transgender patient and 91.0% evaluated the usefulness of the presentation to be very good or excellent. Qualitative analysis (phenomenological study) was conducted on the self-reflection papers and revealed 7 major themes. CONCLUSION: First-year students reported that they found the panel discussion to be eye opening and relevant to their pharmacy career. Our panel may serve as model for other pharmacy schools to implement

The Need for Transgender Health Content in the Pharmacy Curriculum

The article, “The Need for Transgender Health Content in the Pharmacy Curriculum,” addresses transgender patients and how they often have complex medical, psychological, and social concerns. According to the article, these patients may not only need to learn to manage complicated medication regimens, which can have significant side effects, but may also face many barriers to treatment. Some of those barriers include difficulties with insurance, fear of discrimination, lack of support, and a mistrust of the healthcare system. Given the important role that medications play in maintaining their quality of life, the article suggests that pharmacists are in a unique position to not only improve the healthcare that transgender patients receive, but also to improve their perceptions of the system. The article also talks about how current literature shows that little has been done to educate pharmacists on the specific needs of the transgender patient. Parkhill and Mathews say that the likelihood that pharmacy students will encounter transgender patients in their pharmacies will increase as more transgender individuals begin to live their lives authentically. And for that reason, they are recognizing the critical need to increase pharmacy student awareness of the healthcare issues facing this population. The article concludes that by increasing education and awareness of the barriers to healthcare that transgender patients face, students will receive the training required to care for their patients in a culturally competent way

Medication adherence in patients with myotonic dystrophy and facioscapulohumeral muscular dystrophy

Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients. The purpose of our study was to survey medication adherence and disease manifestations in patients enrolled in the NIH-supported National DM and FSHD Registry. The study was completed by 110 DM1, 49 DM2, and 193 FSHD patients. Notable comorbidities were hypertension in FSHD (44 %) and DM2 (37 %), gastroesophageal reflux disease in DM1 (24 %) and DM2 (31 %) and arrhythmias (29 %) and thyroid disease (20 %) in DM1. Each group reported high levels of adherence based on regimen complexity, medication costs, health literacy, side effect profile, and their beliefs about treatment. Only dysphagia in DM1 was reported to significantly impact medication adherence. Approximately 35 % of study patients reported polypharmacy (taking 6 or more medications). Of the patients with polypharmacy, the DM1 cohort was significantly younger (mean 55.0 years) compared to DM2 (59.0 years) and FSHD (63.2 years), and had shorter disease duration (mean 26 years) compared to FSHD (26.8 years) and DM2 (34.8 years). Future research is needed to assess techniques to ease pill swallowing in DM1 and to monitor polypharmacy and potential drug interactions in DM and FSHD

Implementing a Substances of Abuse Outreach Program in the Rochester City School District.

Objective: This program aims to provide substances of abuse education to local high school students. Methods: An outreach program, modeled after the National Institute on Drug Abuse instructional materials, was developed by student pharmacists and faculty for delivery to the Rochester City School District. Strict regulations prevented admittance into any classrooms until the program was presented to all health teachers at a district-wide meeting. Approval was given to begin working in the classrooms in April 2011. The program was first adopted in two health education classes at Edison Tech (May 2011). Information was presented to students using lecture, small group discussion, and printed materials. The topic covered, marijuana, was based on the teacher\u27s preference. A formative assessment was used to address student perceptions of the program due to the small number of students in each of the classes (n = 5–7). The teacher of record in the classroom conducted the assessment interviews. Results: Student feedback included comments such as, “We liked them and appreciate the time they took to come in,” “I didn\u27t know about pharm parties” and, “I learned a lot”. Feedback from the teacher also reflected the positive impact of the program in his classroom: “There is a perception that the outside community does not care about urbanites and this program at the very root reverses that dynamic very clearly. My hope is that we can develop an ongoing relationship.” Conclusion: The timing of program approval by the school district impeded broad implementation for spring 2011; however, plans are in place for several schools in spring 2012. The opportunity to pilot the program with Edison Tech was beneficial and provided valuable feedback for improvement. Student pharmacists are in a unique position to provide this education and are viewed as approachable and non-threatening to high school–aged students

O-Antigen-Dependent Colicin Insensitivity of Uropathogenic Escherichia coli.

The outer membrane of Gram-negative bacteria presents a significant barrier for molecules entering the cell. Nevertheless, colicins, which are antimicrobial proteins secreted by Escherichia coli, can target other E. coli cells by binding to cell surface receptor proteins and activating their import, resulting in cell death. Previous studies have documented high rates of nonspecific resistance (insensitivity) of various E. coli strains toward colicins that is independent of colicin-specific immunity and is instead associated with lipopolysaccharide (LPS) in the outer membrane. This observation poses a contradiction: why do E. coli strains have colicin-expressing plasmids, which are energetically costly to retain, if cells around them are likely to be naturally insensitive to the colicin they produce? Here, using a combination of transposon sequencing and phenotypic microarrays, we show that colicin insensitivity of uropathogenic E. coli sequence type 131 (ST131) is dependent on the production of its O-antigen but that minor changes in growth conditions render the organism sensitive toward colicins. The reintroduction of O-antigen into E. coli K-12 demonstrated that it is the density of O-antigen that is the dominant factor governing colicin insensitivity. We also show, by microscopy of fluorescently labelled colicins, that growth conditions affect the degree of occlusion by O-antigen of outer membrane receptors but not the clustered organization of receptors. The result of our study demonstrate that environmental conditions play a critical role in sensitizing E. coli toward colicins and that O-antigen in LPS is central to this role.IMPORTANCEEscherichia coli infections can be a major health burden, especially with the organism becoming increasingly resistant to "last-resort" antibiotics such as carbapenems. Although colicins are potent narrow-spectrum antimicrobials with potential as future antibiotics, high levels of naturally occurring colicin insensitivity have been documented which could limit their efficacy. We identify O-antigen-dependent colicin insensitivity in a clinically relevant uropathogenic E. coli strain and show that this insensitivity can be circumvented by minor changes to growth conditions. The results of our study suggest that colicin insensitivity among E. coli organisms has been greatly overestimated, and as a consequence, colicins could in fact be effective species-specific antimicrobials targeting pathogenic E. coli such as uropathogenic E. coli (UPEC)

The secondary resistome of multidrug-resistant Klebsiella pneumoniae.

Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the "secondary resistome". As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial "helper" drugs that restore the efficacy of existing antimicrobials