Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits.

Antisecretory medications, primarily proton pump inhibitors (PPIs), have proven effective in reducing upper gastrointestinal toxicities, including upper gastrointestinal bleeding (UGIB), associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are among the most commonly used medications in the United States.1 Accordingly, professional guidance recommends PPIs for patients at high risk for UGIB.2-4 However, little is known about trends in use of antisecretory medications for gastrointestinal prophylaxis ("gastroprotection"). Herein, we examined contemporary use and prescribing of antisecretory medications in visits by patients at high risk for UGIB, relative to visits by patients diagnosed with acid-related disorders.

Emerging therapies for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus that is quickly becoming a more recognized cause of esophageal dysfunction and dysphagia. The cause of EoE is thought to be due to an inflammatory response triggered by exposure to dietary or environmental antigens. Symptoms may be progressive and include reflux, nausea, vomiting, dysphagia, and reduction in quality of life. Both children and adults may be affected. Initial treatments for EoE have focused on elimination diets to potentially identify and remove dietary triggers, acid suppression with proton pump inhibitors, and topical delivery of orally administered swallowed corticosteroids. These therapies are often ineffective in a large proportion of patients, leading to exploration of other approaches by focusing on cytokines involved in the inflammatory response. Most recently, dupilumab, a monoclonal antibody targeting IL-4 received approval for use in patients aged 12 years or older with EoE. Use of dupilumab has seen favorable improvements in disease progression and symptoms with chronic use. Other therapies targeting IL-5, such as mepolizumab, reslizumab, and benralizumab are currently being studied for use in EoE. Therapies targeting other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1-phosphate receptor (etrasimod) are currently being evaluated in clinical trials.

Decisional Guidance Tool for Antibiotic Prescribing in the Skilled Nursing Facility.

OBJECTIVES: To derive weighted-incidence syndromic combination antibiograms (WISCAs) in the skilled nursing facility (SNF). To compare burden of resistance between SNFs in a region and those with and without protocols designed to reduce inappropriate antibiotic use. DESIGN: Retrospective analysis of microbial data from a regional laboratory. SETTING: We analyzed 2484 isolates collected at a regional laboratory from a large mixed urban and suburban area from January 1, 2015, to December 31, 2015. PARTICIPANTS: A total of 28 regional SNFs (rSNFs) and 7 in-network SNFs (iSNFs). MEASUREMENTS: WISCAs were derived combining Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and reports restricted to fluoroquinolones, cefazolin, amoxicillin clavulanate, and trimethoprim/sulfamethoxazole. RESULTS: Pooling the target isolates into WISCAs resulted in an average of 28 of 37 achieving a number greater than 30 with an average of 50 isolates (range = 11-113; >97% urinary). Significant differences were found in antibiotic susceptibility between grouped rSNF data and iSNF data of 75% vs 65% (2.76-11.77; P = .002). The susceptibilities were higher in iSNFs with active antibiotic reduction protocols compared with iSNFs without protocols and rSNFs (effect size = .79 vs .67 and .65, respectively) (I2 = 93.33; P < .01). Susceptibilities to cefazolin (95% vs 76%; P < .001) and fluoroquinolones (72% vs 64%; P = .048) were significantly higher in iSNFs with active urinary tract infection protocols as compared with iSNFs without antibiotic reduction protocols. CONCLUSION: These results suggest that WISCAs can be developed in most SNFs, and their results can serve as indicators of successful antibiotic stewardship programs. J Am Geriatr Soc 68:55-61, 2019.

Trends in Warfarin Monitoring Practices Among New York Medicare Beneficiaries, 2006-2011.

Anticoagulation with warfarin requires frequent evaluation of the international normalized ratio (INR), and less invasive testing devices are available for use by clinicians at the point-of-care (POC) and by patients who self-test (PST). Despite commercial availability and positive results of published studies, evidence suggests that adoption of less invasive (POC/PST) testing in the United States is slow. Considering the equivalence of results and logistical advantages of POC/PST testing, slow uptake may indicate a gap in quality of care warranting evaluation and possibly intervention. This study used Medicare fee for service claims data to explore the uptake of POC/PST INR monitoring across New York State over a 6 year time frame (2006-11), with additional analyses based on beneficiary age, sex, race and ethnicity and income by county. In 2006, only 28.3% of 103,410 analyzable beneficiaries presumed to be chronic warfarin users based on INR testing patterns were monitored by POC/PST, and increased to only 37.6% by 2011. Utilization of POC/PST testing varied widely by county (baseline range 1.2-89.4%), and uptake of these testing modalities in New York State was significantly lower among the very elderly, women, and ethnic minorities. We hypothesize that poor penetration of these less invasive INR testing modalities into highly populated New York City and barriers to POC utilization in long term care facilities may account for a portion of the variability in INR testing patterns observed in this study. However, additional research is needed to further explore whether disparities in warfarin monitoring practices exist.

US-Based Drug Cost Parameter Estimation for Economic Evaluations.

INTRODUCTION: In the United States, more than 10% of national health expenditures are for prescription drugs. Assessing drug costs in US economic evaluation studies is not consistent, as the true acquisition cost of a drug is not known by decision modelers. Current US practice focuses on identifying one reasonable drug cost and imposing some distributional assumption to assess uncertainty. METHODS: We propose a set of Rules based on current pharmacy practice that account for the heterogeneity of drug product costs. The set of products derived from our Rules, and their associated costs, form an empirical distribution that can be used for more realistic sensitivity analyses and create transparency in drug cost parameter computation. The Rules specify an algorithmic process to select clinically equivalent drug products that reduce pill burden, use an appropriate package size, and assume uniform weighting of substitutable products. Three diverse examples show derived empirical distributions and are compared with previously reported cost estimates. RESULTS: The shapes of the empirical distributions among the 3 drugs differ dramatically, including multiple modes and different variation. Previously published estimates differed from the means of the empirical distributions. Published ranges for sensitivity analyses did not cover the ranges of the empirical distributions. In one example using lisinopril, the empirical mean cost of substitutable products was $444 (range = $23-$953) as compared with a published estimate of $305 (range = $51-$523). CONCLUSIONS: Our Rules create a simple and transparent approach to creating cost estimates of drug products and assessing their variability. The approach is easily modified to include a subset of, or different weighting for, substitutable products. The derived empirical distribution is easily incorporated into 1-way or probabilistic sensitivity analyses.

Pain responsiveness to opioids: central versus peripheral neuropathic pain.

Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. Neuropathic pain is composed of peripheral neuropathic pain (with a primary lesion or dysfunction in the peripheral nervous system) and central neuropathic pain (CNP; with a primary lesion or dysfunction in the central nervous system). CNP may be further subdivided into supraspinal central neuropathic pain and spinal central neuropathic pain. Opioids have a role in the pharmacologic management of neuropathic pain; however, there is a scarcity of literature on the treatment of CNP with opioids. One of the few statements in the literature regarding the analgesic efficacy of opioids for CNP suggests that despite limited data, the opioid responsiveness for neuropathic pain of central and peripheral etiologies is similar. After reviewing the extremely limited data, it is proposed that although there may be a subpopulation of patients with CNP who have a reasonable analgesic response to opioids, overall, when sensory pain rating is used as the yardstick, CNP appears to respond less well to opioids than peripheral neuropathic pain. Thus, opioids should be considered a second- or third-line agent in any algorithm of the pharmacologic treatment of CNP. Also within CAP, it appears that supraspinal central neuropathic pain may respond less well to a trial of opioids than spinal central neuropathic pain. Moreover, under close monitoring for side effects (eg, constipation), it is suggested that clinicians may want to consider titrating to higher doses of potent opioids before the trial is judged to be unsuccessful for refractory supraspinal central neuropathic pain.

Increasing frequency of opioid prescriptions for chronic abdominal pain in US outpatient clinics.

BACKGROUND & AIMS: Opioids are sometimes used to treat chronic abdominal pain. However, opioid analgesics have not been proven to be an effective treatment for chronic abdominal pain and have been associated with drug misuse, constipation, and worsening abdominal pain. We sought to estimate the national prescribing trends and factors associated with opioid prescribing for chronic abdominal pain. METHODS: Chronic abdominal pain-related visits by adults to US outpatient clinics were identified using reason-for-visit codes from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (1997-2008). Data were weighted to produce national estimates of opioid prescriptions over time. Logistic regression analyses, adjusted for complex survey design, were performed to identify factors associated with opioid use. RESULTS: The number of outpatient visits for chronic abdominal pain consistently decreased over time from 14.8 million visits (95% confidence interval [CI], 11.6-18.0 visits) in 1997 through 1999 to 12.2 million visits (95% CI, 9.0-15.6 visits) or 1863 visits per 100,000 population in 2006 through 2008 (P for trend = 0.04). Conversely, the adjusted prevalence of visits for which an opioid was prescribed increased from 5.9% (95% CI, 3.5%-8.3%) in 1997 through 1999 to 12.2% (95% CI, 7.5%-17.0%) in 2006 through 2008 (P = 0.03 for trend). Opioid prescriptions were most common among patients aged 25 to 40 years old (odds ratio [OR] 4.6; 95% CI, 1.2-18.4). Opioid prescriptions were less common among uninsured (OR 0.1; 95% CI, 0.04-0.40) and African American (OR 0.3; 95% CI, 0.1-0.9) patients. CONCLUSIONS: From 1997 to 2008 opioid prescriptions for chronic abdominal pain more than doubled. Further studies are needed to better understand the reasons for and consequences of this trend.

Overactive bladder drugs and constipation: a meta-analysis of randomized, placebo-controlled trials.

BACKGROUND: Anticholinergic drugs are commonly prescribed for symptomatic treatment of overactive bladder (OAB). While recent meta-analyses have characterized the prevalence of dry mouth among patients utilizing OAB medications, prevalence of constipation has not been systematically reviewed. AIMS: To provide an effect measure for constipation associated with anticholinergic OAB drugs versus placebo. METHODS: A meta-analysis of trials with darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium was conducted. All randomized, placebo-controlled studies of anticholinergic OAB drugs published in English language and identified in Medline and Cochrane databases were considered for inclusion in this meta-analysis. Those meeting predetermined design characteristics and having sufficient duration (≥2 weeks) were included. Constipation-related data from all included studies were abstracted. RESULTS: One hundred two English-language, randomized, placebo-controlled trials were originally identified. Thirty-seven studies were ultimately included in the analysis, involving 19,434 total subjects (12,368 treatment+7,066 placebo patients). The odds ratios for constipation compared with placebo were as follows: overall [odds ratio (OR) 2.18, 95% confidence interval (CI)=1.82-2.60], tolterodine (OR 1.36, 95% CI=1.01-1.85), darifenacin (OR 1.93, 95% CI=1.40-2.66), fesoterodine (OR 2.07, 95% CI=1.28-3.35), oxybutynin (OR 2.34, 95% CI=1.31-4.16), trospium (OR 2.93, 95% CI=2.00-4.28), and solifenacin (OR 3.02, 95% CI=2.37-3.84). CONCLUSIONS: Our results demonstrate that patients prescribed anticholinergic OAB drugs are significantly more likely to experience constipation. Differences in muscarinic receptor affinities among individual agents may possibly account for the modest variation in constipation rates observed; however, such a determination warrants additional research.

ACCP: economic evaluations of clinical pharmacy services: 2001-2005.

The objectives of this review were to summarize and evaluate studies that measured the economic impact of clinical pharmacy services published between 2001 and 2005 (inclusive) and to provide guidance on methodologic considerations to individuals performing such research in the future. A systematic literature search using the MEDLINE and International Pharmaceutical Abstracts databases was conducted to identify published economic evaluations of clinical pharmacy services. Studies were screened and then randomly assigned to reviewers, who reassessed inclusion and exclusion criteria and abstracted prespecified data from each study. Among the many characteristics examined in each study were study design and type of economic evaluation, setting and type of clinical pharmacy service, study quality, and results. Ninety-three articles were included in the final analysis. These studies were published in 43 different journals, most of which (68 [73.1%]) were pharmacy-based. Most studies were performed in hospitals (40 [43.0%]), ambulatory care clinics or physician's offices (20 [21.5%]), or community pharmacies (16 [17.2%]). The most common types of clinical pharmacy services evaluated were general pharmacotherapeutic monitoring services (32 [34.4%]), target drug programs (27 [29%]), and disease state-management services (21 [22.6%]). Full economic evaluations were performed in just less than half (45 [48.4%]) of the studies, and a positive economic benefit associated with clinical pharmacy services was noted in 31 (69%) of the 45 studies. Among 15 studies reporting data necessary to determine a benefit:cost ratio, the pooled median value was 4.81:1-meaning that for every $1 invested in clinical pharmacy services, $4.81 was achieved in reduced costs or other economic benefits. The quality of studies varied widely, with less than one half considered to be good to fair (40 [43.0%]); however, the proportion of studies using appropriate study designs increased compared with previous reviews. Based on the evidence examined in this review, clinical pharmacy services continue to provide a significant return on investment, but improvements are still needed in the methods used to evaluate the economic impact of these services.

Ambulatory care for constipation in the United States, 1993-2004.

OBJECTIVES: Chronic constipation is one of the most common disorders seen in primary care. In order to examine longitudinal changes in the ambulatory care that occur in constipation evaluation and management, we examined national trends in physician office visits associated with constipation between 1993 and 2004. METHODS: Data were derived from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Care Survey (NHAMCS) for 1993-2004. Patient visits were classified as encounters for constipation-related care. Analyses were performed by combining 4 yr of data (1993-1996, 1997-2000, and 2001-2004). RESULTS: Ambulatory visits for constipation increased from 4 million (95% CI 3.3-4.7 million) ambulatory visits for constipation annually during 1993-1996 period to 7.95 million (95% CI 6.6-9.4 million) visits during the 2001-2004 period. The proportion of medical visits for constipation increased for pediatricians, but decreased for adult primary care providers from 1993 to 2004. During the observed time period, the proportion of medical visits for constipation did not change for gastroenterologists. The primary treatment for constipation shifted from bulking agents (fiber) to osmotic laxatives. CONCLUSION: There has been a significant increase in physician office visits for constipation between 1993 and 2004, with the highest rate of increase in the pediatric population. Longitudinal trends indicate an increase in constipation-related visits for pediatricians. The primary treatment for constipation among medical providers shifted from using bulking agents to osmotic laxatives for unknown reasons.

Evidence of the economic benefit of clinical pharmacy services: 1996-2000.

We sought to summarize and assess original evaluations of the economic impact of clinical pharmacy services published from 1996-2000, and to provide recommendations and methodologic considerations for future research. A systematic literature search was conducted to identify articles that were then blinded and randomly assigned to reviewers who confirmed inclusion and abstracted key information. Results were compared with those of a similar review of literature published from 1988-1995. In the 59 included articles, the studies were conducted across a variety of practice sites that consisted of hospitals (52%), community pharmacies and clinics (41%), health maintenance organizations (3%), and long-term or intermediate care facilities (3%). They focused on a broad range of clinical pharmacy services such as general pharmacotherapeutic monitoring (47%), target drug programs (20%), disease management programs (10%), and patient education or cognitive services (10%). Compared with the studies of the previous review, a greater proportion of evaluations were conducted in community pharmacies or clinics, and the types of services evaluated tended to be more comprehensive rather than specialized. Articles were categorized by type of evaluation: 36% were considered outcome analyses, 24% full economic analyses, 17% outcome descriptions, 15% cost and outcome descriptions, and 8% cost analyses. Compared with the studies of the previous review, a greater proportion of studies in the current review used more rigorous study designs. Most studies reported positive financial benefits of the clinical pharmacy service evaluated. In 16 studies, a benefit:cost ratio was reported by the authors or was able to be calculated by the reviewers (these ranged from 1.7:1-17.0:1, median 4.68:1). The body of literature from this 5-year period provides continued evidence of the economic benefit of clinical pharmacy services. Although the quality of study design has improved, whenever possible, future evaluations of this type should incorporate methodologies that will further enhance the strength of evidence of this literature and the conclusions that may be drawn from it.

Risk factors for anti-inflammatory-drug- or aspirin-induced gastrointestinal complications in individuals receiving outpatient physical therapy services.

STUDY DESIGN: Prospective, multicenter, observational research study. BACKGROUND: Minimal research exists that describes the potential for serious gastrointestinal complications in individuals receiving outpatient physical therapy care. OBJECTIVE: To identify the prevalence of risk factors for gastrointestinal complications induced by anti-inflammatory drugs or aspirin in individuals receiving outpatient physical therapy services. METHODS AND MEASURES: A self-administered questionnaire was used at 65 ambulatory physical therapy clinics to document past medical history, history of present illness, and medication use. Risk factors for anti-inflammatory-drug- or aspirin-induced gastrointestinal complications were identified and the proportion of patients reporting each factor was determined. RESULTS: A total of 2433 patients completed the survey. Of the 2311 evaluable patients included in the study, 78.6% reported over-the-counter or prescribed use of an anti-inflammatory drug or aspirin during the week prior to the survey. Forty-nine percent of the patients reported at least 1 risk factor for drug-induced gastrointestinal complications, while 12.9% reported 2 or more risk factors. The most frequently reported established risk factors among anti-inflammatory drug or aspirin users were (1) combination (dual) therapy (22.3% reported concomitant use of anti-inflammatory and aspirin therapy), (2) advanced age (15.7% were over the age of 61 years), (3) history of peptic ulcer disease (7.8% had a history of peptic ulcer disease), and (4) significant systemic illness (6.8% reported having rheumatoid arthritis or heart disease). A frequently encountered risk factor combination was advanced age with a history of peptic ulcer disease (12.7%). CONCLUSIONS: Patients seen at physical therapy ambulatory clinics present with multiple risk factors for anti-inflammatory-drug- or aspirin-induced gastrointestinal complications and provide a potential opportunity for risk reduction by clinicians working in this environment.

Regional variation in stroke mortality in Wisconsin, 1989-1998.

OBJECTIVE: To evaluate the regional variation in stroke mortality and determine the level of excess stroke mortality in Wisconsin over the period 1989-1998. METHODS: Wisconsin stroke mortality (ICD-9 430-438) data from the Center for Disease Control and Prevention (CDC WONDER) were analyzed by county for the period 1989-1998 using indirect age standardization. RESULTS: Estimates of observed and excess number of deaths associated with cerebrovascular disease in Wisconsin varied considerably by county during the 10-year time frame studied. Twenty-five counties had an observed number of stroke deaths that were statistically significantly different from what was expected given the age structure of their population. Of these, 14 had significantly more deaths than expected while 11 had significantly fewer. DISCUSSION: There is substantial variation in stroke mortality between Wisconsin counties. Potential reasons for regional variation are unknown and warrant further research. This paper may give Wisconsin counties a benchmark of their progress in preventing stroke mortality to date and give direction for future public health efforts.

Pharmacy-based bone mass measurement to assess osteoporosis risk.

OBJECTIVE: To evaluate elderly women's knowledge of their skeletal status, assess adequacy of calcium intake, determine the prevalence of low bone density, and determine whether peripheral bone density testing led to medical interventions in a group of rural, elderly Wisconsin women recruited in community pharmacies. DESIGN: Recruiting notices were posted in each pharmacy, and eligible women were enrolled in the order in which they volunteered. Each completed a fracture-risk questionnaire. Calcaneal bone density was measured within the following 6 weeks, using peripheral dual-energy X-ray absorptiometry. Mail surveys were used to assess interventions subsequent to the womens' study participation. SETTING: The study was conducted at 5 community pharmacies in rural Wisconsin. RESULTS: Of 133 women, 20% had calcaneal osteoporosis, defined as a T score < or =2.5 (calcaneal bone density <2.5 SDs below the young reference database). Thirty percent of women met National Osteoporosis Foundation (NOF) treatment criteria based on heel bone density and NOF-designated risk factors. Of those meeting treatment criteria, 75% were unaware of their low bone mass. Half of the women received <1200 mg/d of calcium, the recommended dose for osteoporosis prevention. Those who were taking a calcium supplement were much more likely to receive the recommended amount. Women who had discussed bone density test results with their physicians were more likely to receive central dual energy X-ray absorptiometry (DXA) measurements and/or start antiresorptive therapy than women who did not. CONCLUSIONS: Rural, elderly Wisconsin women are at substantial risk for osteoporosis, based on calcaneal bone density, but most are unaware of their risk. Compounding this risk is low calcium intake. Community screening of rural, elderly women by peripheral bone density measurement can lead to medical interventions in such individuals.

Osteoporosis screening by community pharmacists: use of National Osteoporosis Foundation resources.

OBJECTIVES: To assess the feasibility of establishing an osteoporosis screening program in rural community pharmacies based on information and resources provided by the National Osteoporosis Foundation (NOF), to survey primary care providers regarding the usefulness of this screening program, and to recommend strategies for pharmacists interested in working with patients at risk for osteoporosis. DESIGN AND PARTICIPANTS: Pharmacists and/or nurses enrolled women 65 years of age and older into the study, measured calcaneal bone density, administered a questionnaire to ascertain subjects' osteoporosis risk factors, and provided NOF literature to subjects. With their agreement, women's bone mass data and risk factor assessments were provided to primary care providers along with NOF's Physician's Guide to Prevention and Treatment of Osteoporosis. These providers were surveyed as to whether they found this information useful. SETTING: Five independent community pharmacies in rural Wisconsin. RESULTS: We enrolled and tested 133 women. Of these, 122 (92%) agreed to have information mailed to their primary health care providers. These 57 providers were surveyed and 24 (42%) responded; of these 24, 20 (83%) found the information they received useful. CONCLUSION: A community pharmacy-based osteoporosis screening program using NOF materials was well accepted by physicians. NOF resources and recommendations can provide a strong foundation for such programs.