Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.

OBJECTIVES: To examine the association between metabolic syndrome (MetS) and frailty, and determine whether co-existent MetS and frailty affect disability-free survival (DFS), assessed through a composite of death, dementia or physical disability. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling older adults from Australia and the United States (n=18,264) from "ASPirin in Reducing Events in the Elderly" (ASPREE) study. MEASUREMENTS: MetS was defined according to American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2018). A modified Fried phenotype and a deficit accumulation Frailty Index (FI) were used to assess frailty. Association between MetS and frailty was examined using multinomial logistic regression. Cox regression was used to analyze the association between MetS, frailty and DFS over a median follow-up of 4.7 years. RESULTS: Among 18,264 participants, 49.9% met the criteria for MetS at baseline. Participants with Mets were more likely to be pre-frail [Relative Risk Ratio (RRR): 1.22; 95%Confidence Interval (CI): 1.14, 1.30)] or frail (RRR: 1.66; 95%CI: 1.32, 2.08) than those without MetS. MetS alone did not shorten DFS while pre-frailty or frailty alone did [Hazard Ratio (HR): 1.68; 95%CI: 1.45, 1.94; HR: 2.65; 95%CI:1.92, 3.66, respectively]. Co-existent MetS with pre-frailty/frailty did not change the risk of shortened DFS. CONCLUSIONS: MetS was associated with pre-frailty or frailty in community-dwelling older individuals. Pre-frailty or frailty increased the risk of reduced DFS but presence of MetS did not change this risk. Assessment of frailty may be more important than MetS in predicting survival free of dementia or physical disability.

The Association between Frailty and All-Cause Mortality in Community-Dwelling Older Individuals: An Umbrella Review.

Frailty is associated with multiple adverse health outcomes, including mortality. Several methods have been used to characterize frailty, each based on different frailty scales. These include scales based on phenotype, multidomain, and deficit accumulations. Several systematic reviews have examined the association between frailty and mortality; however, it is unclear whether these different frailty scales similarly predict mortality. This umbrella review aims to examine the association between frailty assessed by different frailty scales and all-cause mortality among community-dwelling older adults. A protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched. Methodological quality was assessed using the JBI critical appraisal checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales; one evaluated Fried's physical frailty phenotype and its modifications; another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All of the systematic reviews found that frailty was significantly associated with all-cause mortality. This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale.

Indication-specific 6-h systolic blood pressure thresholds can approximate 24-h determination of blood pressure control.

Ambulatory blood pressure monitoring (ABPM) is an accurate method for evaluating hypertension, yet its use in clinical practice may be limited by availability, cost and patient inconvenience. The objective of this study was to investigate the ability of a 6-h ABPM window to predict blood pressure control, judging by that of the full 24-h ABPM session across several clinical indications in a cohort of 486 patients referred for ABPM. Sensitivities and specificities of the 6-h systolic blood pressure mean to accurately classify patients as hypertensive were determined using a fixed reference point of 130 mm Hg for the 24-h mean. For four common indications, in which ABPM was ordered, prediction tables were constructed varying the thresholds for the 6-h mean to find the optimal value that best predicted the 24-h hypertensive status as determined from the full 24-h interval. Using a threshold of 137 mm Hg for the indications of borderline hypertension, evaluation of current antihypertensive regimen and suspected white-coat hypertension, sensitivity and specificity ranged from 0.83-0.88 to 0.80-0.88, respectively, for the ability of 6-h ABPM to correctly categorize hypertensive status. Using 133 mm Hg as the threshold for treatment resistance resulted in a sensitivity and specificity of 0.93 and 0.83, respectively. We conclude that a shortened ABPM session of 6 h can be used to accurately classify blood pressure as controlled or not, based on the results of a 24-h session. The optimal 6-h threshold for comparison depends upon indication for referral.

Do antibiotics affect the quality of life of patients with upper respiratory tract illnesses? It might depend on one's luck.

OBJECTIVE: Upper respiratory tract illnesses (URTI) are known to cause measurable decline in health-related quality of life (HRQL). We studied whether antibiotics impacted patients' HRQL after obtaining medical care for URTI. METHODS: Adults seeking care for URTI at a family medicine office were eligible for this study. Decisions to prescribe antibiotics were left to their physicians. Subjects completed the Quality of Well-Being questionnaire on enrolment and on days 3, 7, 14 and 28. Analysis of HRQL was undertaken using repeated measures ANOVA and ANCOVA. RESULTS: Seventy-three patients (mean age 35.8 years) were studied. Thirty-six of the subjects (50.7%) received prescriptions for antibiotics from their physicians at the index visit. By day 28, 78.4% of the subjects in the antibiotic group and 77.8% of the other group reported cure (p = 0.95). Receiving a prescription for an antibiotic at the initial visit did not influence subsequent HRQL reported by subjects (p = 0.98). However, when subjects receiving antibiotics were subgrouped by whether they reported an antibiotic adverse event we found significant differences in final HRQL. Subjects receiving antibiotics but not experiencing adverse events reported higher HRQL by day 28 than did subjects receiving an antibiotic but also reporting adverse events and subjects not receiving any antibiotics (p = 0.02). CONCLUSION: Providing patients experiencing URTIs with prescriptions for antibiotics does not, on average, positively impact HRQL over the following 28 days. However, the subgroup of patients who receive antibiotics and do not experience an adverse event may come out ahead.

Use of point-of-service health status assessments by community pharmacists to identify and resolve drug-related problems in patients with musculoskeletal disorders.

STUDY OBJECTIVE: To determine whether community pharmacists can use point-of-service health status assessments to identify and resolve drug-related problems (DRPs) in ambulatory patients with selected musculoskeletal (MSK) disorders. DESIGN: Twelve-month, prospective, multicenter demonstration project. SETTING: Twelve independent community pharmacies in eastern Iowa. PATIENTS: Ambulatory patients with self-reported diagnosis of osteoarthritis, rheumatoid arthritis, or low back pain. MEASUREMENTS: During quarterly pharmacy visits for 1 year, patients used touch-screen computers to report their health status. Patients answered questions on the Short Form-36 (SF-36) general health survey, as well as questions assessing limitations associated with their MSK condition. Pharmacists used this data in interviewing patients to assess for DRPs. MAIN RESULTS: The study enrolled 461 patients, of whom 388 returned for the 12-month visit. During this 1-year period, community pharmacists identified 926 cumulative DRPs. Patients with no DRPs had significantly higher physical component summary scores on the SF-36 (p<0.05) than patients with more than one DRP at baseline (36.2 vs 31.6), 6 months (39.2 vs 33.3), and 12 months (40.1 vs 35.4). At 12 months, actions performed by pharmacists led to resolution or improvement of 70.7% of DRPs. CONCLUSION: Drug-related problems are numerous in community-dwelling patients with MSK disorders and correspond to decreased physical health status. Community pharmacists can use patient-reported measures of health status to identify DRPs and initiate processes to resolve them.

Leukotriene receptor antagonists in the treatment of allergic rhinitis.

OBJECTIVE: To review the literature examining the clinical use of leukotriene receptor antagonists in the treatment of allergic rhinitis. DATA SOURCES: Biomedical literature accessed through MEDLINE (1990-November 2000) and Current Contents (week 35 of 1999 to week 48 of 2000). Key terms included leukotriene antagonists, montelukast, zafirlukast, and rhinitis (allergic). DATA SYNTHESIS: Preliminary evidence on the clinical use of either montelukast or zafirlukast as monotherapy is equivocal, with one study noting benefit and another noting lack of benefit in symptom amelioration. A third study suggests that these agents may have a role in further modifying allergic rhinitis symptoms when used in combination with standard treatments. CONCLUSIONS: Future large-scale studies should assess the efficacy of these agents in the treatment of allergic rhinitis, in particular, to identify subsets of patients likely to derive the most benefit. Available data suggest it is reasonable and safe to add these agents to standard therapy if symptomatology remains unresolved.

Newer dopamine agonists in the treatment of restless legs syndrome.

OBJECTIVE: To review the use of newer dopamine agonists pramipexole and ropinirole, in the treatment of restless legs syndrome (RLS). DATA SOURCES: Biomedical literature was accessed through MEDLINE (1990-June 2000); key terms included restless legs syndrome, pramipexole, ropinirole, and dopamine agonists. References cited in those articles were also evaluated. DATA SYNTHESIS: A number of small clinical studies of short duration have examined the use of pramipexole and ropinirole in the treatment of RLS. Patients treated with either agent demonstrated marked improvement in RLS symptoms with minimal adverse effects. Recent postmarketing surveillance of the use of these drugs for Parkinson's disease reported problems with daytime somnolence; thus, patients should be counseled appropriately. CONCLUSIONS: Although the published trials show promising results for efficacy of pramipexole and ropinirole in the treatment of RLS, they are subject to many limitations. At present, these agents can be considered a reasonable alternative after failure of traditional therapies for RLS, such as carbidopa/levodopa. The encouraging results underscore the need for a large double-blind study comparing pramipexole and ropinirole with traditional agents.

Physician perceptions about administration of immunizations outside of physician offices.

BACKGROUND: Expanding nonphysician participation in the administration of immunizations has been suggested as a means of increasing immunization rates. However, there is little information about physician interest in collaborating with nonphysicians to provide out-of-office immunizations. METHODS: All active members of the Iowa Academy of Family Physicians were surveyed by mail. Physicians reported on their collaboration histories, their willingness to collaborate in the future, their concerns with collaboration, and whether they approved of their patients' using nonphysicians for immunizations. RESULTS: Of 898 eligible physicians, 476 (53%) returned questionnaires that were analyzed. Seventy-five percent (n = 357) of the physicians reported that they had voluntarily collaborated with a person outside their office to provide immunizations. Ninety-five percent (n = 452) of physicians indicated a willingness to collaborate in some form in the future. However, physicians had concerns about (a) being able to be kept informed about immunizations their patients receive outside of their offices, (b) adequate training of the nonphysician to administer immunizations and respond to complications of immunization, and (c) loss of preventive health opportunities if patients ceased coming to physicians for routine immunizations. CONCLUSION: The majority of family physicians have collaborated to deliver immunizations and indicate support for nonphysician participation. Almost all physicians would consider future collaborative arrangements although they have concerns about record keeping and the safety of out-of-office immunization programs.

Patients' acceptance of traditional and nontraditional immunization providers.

OBJECTIVE: To examine patients' acceptance and reported use of traditional and nontraditional immunization providers and settings. DESIGN: Survey. SETTING: Stratified sample of private family physician clinics, family medicine residency training programs, community pharmacies that provide immunizations under standing order protocols, and nonimmunizing community pharmacies, all located in Iowa. PATIENTS OR OTHER PARTICIPANTS: Individuals presenting for medical care or pharmacy services. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sources of past immunizations, 'access to immunizations, importance of immunization records, and future use of different health care providers and settings for immunizations. Univariate and multivariate analyses were performed to examine the relationships between patient demographics and recruitment site on the question responses. RESULTS: 420 surveys were returned (67% response rate). Respondents frequently received immunizations at sites other than physician offices. Younger patients and those living in smaller towns were more likely to report receiving an immunization from a nonphysician. Patients recruited in immunizing pharmacies more often reported previous immunization by a pharmacist (P < .001), most often for influenza. Respondents often reported that it was more convenient to receive an immunization outside a physician office. Greater support was noted for receiving adult immunizations from nonphysicians and in nontraditional settings, whereas traditional settings and providers (physician offices, community health departments) were preferred for childhood immunizations. CONCLUSION: Iowans report accessing different health care providers and settings for their routine immunizations. In general, they are more likely to support using traditional immunization providers and settings for childhood immunizations but are less exclusive about where they receive adult immunizations. Pharmacists should consider focusing initial efforts on administering adult immunizations, due to greater patient acceptance of nontraditional immunizers for adult immunizations.

Use of metformin in polycystic ovary syndrome.

OBJECTIVE: To review the use of the insulin-sensitizing agent metformin in women with polycystic ovary syndrome (PCOS). DATA SOURCES: Biomedical literature was accessed through MEDLINE (1996-March 2001) and the Iowa Drug Information Service. Key terms included metformin and polycystic ovary syndrome. DATA SYNTHESIS: A number of small clinical studies have examined the use of metformin in the treatment of PCOS. Women treated with metformin demonstrated normalization of endocrine function with minimal adverse effects. CONCLUSIONS: Metformin can be beneficial in normalizing menstrual irregularities and stimulating ovulation in previously anovulatory women. Metformin therapy is well tolerated by the majority of patients and should be considered for use in women with PCOS.

Prescription medication costs: a study of physician familiarity.

BACKGROUND: Studies in the past 25 years have suggested that physicians are not familiar with the costs of common prescription medications. OBJECTIVES: To determine physician familiarity with the cost of common prescription medications and to determine the value physicians place on knowing information regarding the cost of medications. DESIGN: Survey. SETTING: Seven community-based family medicine residency teaching clinics in Iowa. PARTICIPANTS: Two hundred five practicing resident and faculty physicians. INTERVENTIONS: From a series of $10 price intervals (range, $0.01-$80.00), physicians were asked to select the interval containing the cash price of the medication to an uninsured patient for 50 medications commonly prescribed in outpatient family medicine clinics. Physicians were also questioned about the value of medication cost information to their practice. MAIN OUTCOME MEASURES: The percentage of correct responses and the mean pricing scores were calculated for each respondent and for all medications. RESULTS: One hundred seventy-eight physicians responded (86.8%). Only 22.9% of the responses correctly identified the cost of the medication. More than two thirds (68.3%) of the responses underestimated the correct price interval. Branded drugs were underestimated in 89.9% of responses, while generic drugs were overestimated in 90.2% of responses. Overall, 64.4% of physicians believed they did not receive sufficient information in their practices regarding prescription drug costs, and nearly all (93.6%) reported that regular information on prescription medication costs would help them prescribe more cost-effectively. CONCLUSIONS: Physicians are unfamiliar with the costs of medications they commonly prescribe, and they report that regular access to information on prescription medication costs would help them prescribe more cost-effectively. Arch Fam Med. 2000;9:1002-1007

Assessment of patients' perceptions and beliefs regarding herbal therapies.

We evaluated the demographics and beliefs regarding safety and efficacy of herbal therapy among individuals in Iowa and assessed the willingness to discuss the use of these products with health care providers. We distributed 1300 surveys to two random samples: patients attending eight clinics, and residents of the state (mailing). Data were categorized according to herb use and compared between users and nonusers. The response rate was 61% (794 people), with 41.6% of respondents reporting herb use. They were predominately white women and were likely to have had education beyond high school (p<0.05). Their use of prescription drugs was high (p<0.05). Although users rated safety and efficacy of herbs higher than nonusers (p<0.05), both groups believed that health care providers should be aware of use and would provide this information.

Current perspectives on the management of seasonal affective disorder.

OBJECTIVE: To concisely review the etiology and current treatment modalities of seasonal affective disorder (SAD). DATA SOURCES: A MEDLINE search (1966-1999) was performed using the search term "seasonal affective disorder." The search was subsequently focused to "drug therapy" with limits of human studies and English-language papers. The search term "light therapy" was combined with "seasonal affective disorder." STUDY SELECTION AND DATA EXTRACTION: Articles discussing the epidemiology and treatment of SAD were independently examined by each author. Additional literature was reviewed from selected references identified by the original articles. DATA SYNTHESIS: SAD most likely results from a deficiency in serotonin. Light therapy remains the therapeutic intervention with the most experience and success. Selective serotonin reuptake inhibitors (SSRIs) have also shown benefit in treating the disorder. CONCLUSION: SAD is an important subtype of major depressive disorder. Clinicians should remain vigilant for signs and symptoms of the illness. Successful treatment may include light therapy or antidepressants, particularly SSRIs.

Effectively treating common infections in residents of long-term care facilities.

Clinicians involved in caring for institutionalized elderly frequently must treat common infections endemic to the setting. Numerous factors specific to these patients make accurate diagnosis and management more difficult than in healthy ambulatory adults. Three infections are commonly encountered in residents of long-term care facilities: bacterial pneumonia, urinary tract infections, and skin and soft tissue infections. More antimicrobial agents are available now than ever before; therefore, judicious administration of drugs and familiarity with current treatment recommendations are imperative.