Elderly patients with chronic obstructive pulmonary disease may be at increased risk of exacerbation due to physical and cognitive deficits that make proper inhaled medication adherence more difficult despite consistent medication access. This retrospective study utilized administrative medical and pharmacy claims data to examine the likelihood of having a COPD exacerbation requiring acute medical care by means of an emergency room visit or hospitalization in elderly patients receiving maintenance COPD medications from mail order and retail pharmacies. It was hypothesized that mail order patients would be more likely to experience exacerbations despite differences in medication access when compared to retail patients. The primary outcome of interest was exacerbation frequency expressed as the incidence density rate, and the secondary outcome was the proportion of days covered (PDC). The incidence rate ratio for acute exacerbations was not significantly different for mail order and retail groups, indicating patients using mail-order pharmacies were not significantly more likely to experience an exacerbation requiring acute medical care. Despite insignificant differences in incidence rates, mail order patients had significantly higher adherence rates.

The study aimed to identify leading practices to promote environmentally friendly and efficient efforts in surgical healthcare. Despite widespread enthusiasm for going green in the U.S. economy, little information is available to inform the medical community on the effort. We explore safe and efficient strategies for hospitals and healthcare providers to protect the environment while delivering high-quality care. As part of the study design, we performed a systematic review of the literature using relevant Pubmed search terms and surveyed a panel of hospital managers and CEOs of healthcare organizations pursuing green initiatives. Recommendations were itemized and reviewed with each panelist for a consensus agreement. At the end, we identified forty-three published articles and obtained interview data from the 7-member expert panel. Five green recommendations for surgical practices were identified: (1) OR Waste Reduction and Segregation; (2) Environmentally Preferable Purchasing; (3) Energy Consumption Management; (4) Pharmaceutical Waste Management; (5) Reprocessing of Single Use Medical Devices. We concluded that the medical community has a large opportunity to implement green practices in surgical units. These practices can have significant benefits to both the healthcare community and the environment.

Background Maternal opioid use and neonatal abstinence syndrome (NAS) incidence have increased markedly in the US in recent years. Objectives (1) To assess prescribers’ and community pharmacists’ guideline-based NAS prevention behaviors; (2) to describe providers’ perceptions of contraceptive appropriateness in female patients of childbearing age. Method Cross-sectional study of 100 randomly selected primary care physicians, 100 prescribers authorized to engage in in-office treatment of opioid use disorders with buprenorphine, 100 pain management clinic directors, and 100 community pharmacists in Tennessee (N = 400 providers total) to evaluate self-reported engagement in 15 NAS prevention behaviors and perceived appropriateness of 8 contraceptive methods in opioid using women of childbearing age. Results An overall response rate of 17.5% was obtained. Pain clinic directors reported the most engagement in NAS prevention, engaging 80% or more of female patients of childbearing age prescribed an opioid in 11 prevention behaviors, followed by buprenorphine prescribers (8 behaviors), primary care physicians (5 behaviors), and community pharmacists (2 behaviors). Pain clinic directors, primary care physicians, and community pharmacists perceived oral contraceptive pills and patches to be as appropriate as long-acting, reversible forms of contraception (e.g., implants, injectable depots, intrauterine devices). Conclusion Provider engagement in behaviors that could prevent NAS is variable. Interventions should be implemented that equip providers to engage patients in conversations about long-acting, reversible contraception.

For patients afflicted with symptoms of anxiety and insomnia, benzodiazepines are generally a safe and effective short-term pharmacological treatment option. Although considered safer than other sedative-hypnotic medications, substantial concern exists regarding the addictive nature and abuse potential of benzodiazepines along with potentially inappropriate prescribing and utilization in clinically vulnerable populations. These medication misadventures can have a significant impact on public health. Examples of medication misadventures as they pertain to benzodiazepines include the prescribing and use in clinically vulnerable populations for whom they are contraindicated or their efficacy has not been evaluated, the development of tolerance or addiction, abuse of the medication, and the manifestation of negative health outcomes including cognitive impairment, withdrawal symptoms upon discontinuation, or the reoccurrence of a preexisting substance use disorder. In order to better understand medication misadventures associated with benzodiazepines retrospective analyses using populations extracted from large health claims databases are employed. To understand how benzodiazepine use may lead to adverse events causing patient harm, the risk of exacerbations in benzodiazepine users diagnosed with chronic obstructive pulmonary disease was estimated. The inherent risk of benzodiazepine addiction and abuse was estimated in an HIV-infected population, a population with a high prevalence of substance use disorders. This risk was estimated by first determining whether HIV-infected individuals are more likely to have any benzodiazepine use compared to their uninfected counterparts, and secondly, by examining the association between HIV-infection and potentially problematic benzodiazepine use. Finally, in an effort to mitigate unexpected and undesirable consequences to public health associated with the prescription drug abuse epidemic in the US, states have implemented prescription drug monitoring programs (PDMPs) to track the prescribing and dispensing of controlled substance medications. The effect of these programs on benzodiazepine dispensing is evaluated on a state and national level. Findings will provide healthcare professionals a better understanding regarding the risk of medication misadventures involving benzodiazepines when evaluating their appropriateness in patients with anxiety, depression, and insomnia. Additionally, policymakers will understand the implications of PDMPs on the dispensing of benzodiazepines as they become a more widely used tool to combat prescription drug abuse and diversion.

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes to indicate that a sentinel lymph node biopsy had been performed. Hormone receptor status was verified by patients receiving at least one month of hormonal therapy including: tamoxifen, anastrozole, letrozole, or exemestane. Exclusion criteria will include patients less than 18 years of age, procedure codes indicating axillary lymph node dissection, or charges for trastuzumab. The administration of Oncotype DX® was not found to significantly affect a physician’s decision to prescribe chemotherapy. However, there were significant regional differences in Oncotype DX® utilization by region. Future studies should be conducted at a population level to determine the effects of Oncotype DX®.

Regardless of the setting, medication errors are of great concern when associated with an individual’s health outcomes, along with the increased costs to society, healthcare institutions, and providers. Current research focuses on medication error data primarily in acute and extended care facilities. However, there is a paucity of research examining the causes of medication errors that occur post hospital discharge when individuals transition to the home. The purpose of this integrative literature review is to examine risk factors for medication errors outside of these settings, specifically in the home. A systematic literature search was conducted using multiple databases for relevant articles in the English language between 2006 to 2017, including CINAHL, MEDLINE, PubMed, and PsycINFO. Search terms included ‘medication errors’, ‘home care’, ‘post-discharge’, ‘hospital readmission’, and ‘medication error risks in the home’. Exclusion criteria included medication errors in acute and extended care settings. The integrative review involved reading, analyzing and selecting articles, and summarizing on a matrix. Findings on occurrences of medication errors in the home included impaired client mental status, confusion related to medication names, limited understanding of medication purpose in the care plan and its side effects, level of health literacy, and client-provider miscommunication in discharge planning. Consistent and conflicting findings are discussed along with gaps in the literature. Limitations and implications for nursing practice, policy, research, and education are also noted.

<p></p> <p><strong><em>Background </em></strong></p> <p>Oral pharmacotherapy has the potential to offer multiple sclerosis patients improved clinical outcomes compared to traditional therapies.</p> <p><strong><em>Objectives </em></strong></p> <p>This review assesses the effects of oral therapies compared to placebo and interferon beta-1a in adults with relapsing-remitting multiple sclerosis (RRMS).</p> <p><strong><em> </em></strong></p> <p><strong><em>Search methods </em></strong></p> <p>We searched the MEDLINE, EMBASE, Cochrane Library, Web of Science (January 1980 to April 2011) and clinincaltrials.gov (April 2011) databases and reference lists of articles. The FDA website was also searched.</p> <p><strong><em>Selection criteria </em></strong></p> <p>Double-blind, placebo-controlled, randomized trials of RRMS patients who were treated with fingolimod, cladribine, laquinimod or interferon beta-1a.</p> <p><strong><em>Data collection and analysis </em></strong></p> <p>Two reviewers independently assessed articles for inclusion. Data extraction and quality assessment was completed by one reviewer and verified for accuracy. Meta-analysis and indirect treatment comparison methods were used to estimate relative measures of efficacy.</p> <p><strong><em>Results </em></strong></p> <p>Although 11 trials involving 7,127 participants were included in this review, only 2,109 (30%) and 1,738 (24%) participants contributed to the direct and indirect estimates respectively, for the primary outcome, annualized relapse rate. Oral therapy and interferon beta-1a had a significantly different rate of relapse compared to placebo (Mean difference [MD] -0.21, 95% confidence interval [CI] -0.27 to -0.16 , p < 0.00001 and MD -0.33 95% CI -0.65 to -0.01). There was a significant risk reduction of 37% and 19% in the number of patients with at least one relapse for oral therapy and interferon beta-1a compared to placebo respectively. Safety analysis favoured placebo for both sets of trials (p=0.002 and p=0.04). Indirect estimates were not significant for all three outcomes however; comparability between direct evidence was noted.</p> <p><strong><em>Conclusions </em></strong></p> <p>Oral pharmacotherapy and interferon beta-1a are effective compared to placebo in controlling relapse rate in patients with RRMS. The indirect measures of effect provide initial estimates of comparative efficacy and incorporation of future evidence will be necessary.</p> / Master of Science (MSc)

QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL or QNOAEL) of a New Molecular Entity (NME) in order to anticipate a safe starting dose for beginning clinical trials. The NOAEL from QBEST (called the QNOAEL) can be calculated using multiple disparate studies in the literature and/or from the lab. The QNOAEL is similar in some ways to the Benchmark Dose Method (BMD) used widely in toxicological research, but is superior to the BMD in some ways. The QNOAEL simulation generates an intuitive curve that is comparable to the dose-response curve. The NOAEL of ellagic acid (EA) is calculated for clinical trials as a component therapeutic agent (in BSN476) for treating Chikungunya infections. Results are used in a simulation based on nonparametric cluster analysis methods to calculate confidence levels on the difference between the Effect and the No Effect studies. In order to evaluate the statistical power of the algorithm, simulated data clusters with known parameters are fed into the algorithm in a separate study, testing the algorithm’s accuracy and precision “Around the Compass Rose” at known coordinates along the circumference of a multidimensional data cluster. The specific aims of the proposed study are to evaluate the accuracy and precision of the QBEST Simulation and QNOAEL compared to the Benchmark Dose Method, and to calculate the QNOAEL of EA for BSN476 Drug Development.

Background Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients. Objectives 1) To assess the economic burden of RCC among older adults in the targeted therapy era 2) To compare the overall survival (OS) and total healthcare cost (THC) among older mRCC patients receiving CN and targeted therapy versus patients receiving targeted therapy alone 3) To describe prescribing patterns of targeted therapies and associated OS and THC among older mRCC patients. Methods This dissertation was conducted using the Surveillance Epidemiology and End Results (SEER) - Medicare linked data. For the first objective, the study included a prevalent cohort of RCC patients from 2013, diagnosed during 2005 - 2013 and continuously enrolled in Medicare. RCC patients were matched to non-cancer beneficiaries using propensity score matching. Generalized linear models estimated the incremental healthcare costs. Incremental total healthcare cost (THC) was multiplied by the estimated number of RCC patients on Medicare to calculate the total economic burden of RCC. For the second objective, we included patients diagnosed with mRCC between 2007-2014 and compared overall survival (OS), and THC between patients who received CN + targeted therapy and targeted therapy alone. A propensity score based inverse probability of treatment weighting (IPTW) method was used to balance the two treatment groups. A Cox proportional hazard model assessed the risk for death and a GLM compared healthcare costs between the groups. For the third objective, patients with mRCC were defined as patients who were diagnosed at stage-IV or at earlier stages but were currently using targeted therapies. Further, we restricted our sample to patients who initiated targeted therapy. We described the frequencies of the most common first and second line targeted therapies. We also described OS and THC per month for clear-cell and non-clear cell mRCC for each therapy and line of therapy. Results The first study included 10,392 each of RCC and control patients. The average THC associated with RCC was $7,419. The average THC was $4,584 for patients diagnosed at stage-I, $4,727 for stage-II, $9,331 for stage-III, and $31,637 for stage-IV. The annual economic burden of RCC on Medicare was estimated to be $1.5 billion. The second study included 471 mRCC patients that received CN + targeted therapy or targeted therapy alone. The median OS from the adjusted survival curves was significantly higher (p Conclusions The economic burden of RCC varied substantially between early stage and metastatic patients. Among mRCC patients, use of CN among targeted therapy users was associated with a higher median OS and similar monthly THC over a lifetime. Sunitinib and everolimus were the most common first and second line targeted therapies among mRCC patients. The descriptive analysis suggested that OS and THC were similar across types of targeted therapy sequences.

Nursing homes are an essential yet understudied provider of cancer-related care for those with complex health needs. Nine percent of nursing home residents have a cancer diagnosis at admission, and it is estimated that one-third of them experience pain on a daily basis. Although pain management is an essential component of disease treatment, few studies have evaluated analgesic medication use among adults with cancer in this setting. Use of opioids, which are the mainstay of pain management in older adults because of their effectiveness in controlling moderate to severe pain, may be significantly related to coverage by the Medicare Part D prescription drug benefit. However, little is known about Medicare Part D’s effects on opioid use in this patient population. A limited body of evidence also suggests that despite known risks of overdose and respiratory depression in opioid-naïve patients treated with long-acting opioids, use of these agents may be common in nursing homes. This dissertation examined access to appropriate and effective pain-related health care services among US nursing home residents, with a special focus on those with cancer. Objectives of this dissertation were to: 1) estimate the prevalence, and identify resident-level correlates, of pain and receipt of analgesic medications; 2) use a quasi-experimental research design to examine the relationship between implementation of Medicare Part D and changes in the use of fentanyl patches and other opioids; and 3) to estimate the prevalence, and identify resident-level correlates, of naïve initiation of long-acting opioids. Data on residents’ health status from the Resident Assessment Instrument/Minimum Data Set (versions 2.0 and 3.0) were linked with prescription drug transaction data from a nationwide long-term care pharmacy (January 2005–June 2007) and the Centers for Medicare and Medicaid Services (January–December 2011). From 2006 to 2007, more than 65% of residents of nursing homes throughout the US with cancer experienced pain (28.3% on a daily basis), among whom 13.5% reported severe pain. More than 17% of these residents who experienced daily pain received no analgesics (95% confidence interval [CI]: 16.0–19.1%), and treatment was negatively associated among those with advanced age, cognitive impairment, feeding tubes, and restraints. These findings coincided with changing patterns in opioid use among residents with cancer, including relatively abrupt 10% and 21% decreases in use of fentanyl patches and other strong opioids, respectively, after the 2006 implementation of Medicare Part D. In the years since Medicare Part D was introduced, some treatment practices in nursing homes have not been concordant with clinical guidelines for pain management among older adults. Among a contemporary population of long-stay nursing home residents with and without cancer, 10.0% (95% CI: 9.4–10.6%) of those who began receiving a long-acting opioid after nursing home admission had not previously received opioid therapy. Odds of naïve initiation of these potent opioids were increased among residents with terminal prognosis, functional impairment, feeding tubes, and cancer. This dissertation provides new evidence on pharmaceutical management of pain and on Medicare Part D’s impact on opioid use in nursing home residents. Results from this dissertation shed light on nursing home residents’ access to pain-related health care services and provide initial directions for targeted efforts to improve the quality of pain treatment in nursing homes.