Impact of changing U.S. demographics on the decline in smoking prevalence, 1980-2010.

INTRODUCTION: U.S. smoking prevalence has been declining over the last several decades. During this time, the population has also experienced changes in its demographic composition, as Americans are living longer and becoming increasingly racially and ethnically diverse. Since smoking rates vary across age and race/ethnicity groups, demographics alone could contribute to changes in smoking prevalence among the general population. We examined the effect of changing age and race/ethnicity distributions on total smoking prevalence from 1980 to 2010. METHODS: Using the National Health Interview Survey weighting scheme, we applied the distribution of smokers across age and race/ethnicity categories for the years 1980 and 2010 to the distribution of adults in those categories for both years. The total number of smokers was summed to determine resulting smoking prevalence. RESULTS: The combined effect of aging and the changing racial/ethnic composition of the U.S. population has contributed 2.1% points to the decline in smoking prevalence. If the age and racial/ethnic demographic composition had not changed since 1980, smoking prevalence would have been 21.3% in 2010 (with rounding)--statistically significantly higher than the reported 19.3%. Of the 3 demographic factors we considered (age, race, and ethnicity), ethnicity--specifically the rising share of Hispanics in the population--is the most important contributor to declines in smoking. CONCLUSIONS: Our changing demographics have had an impact on smoking prevalence over the last 3 decades. Future declines in smoking may be driven even more by the aging of the population and increasing racial and ethnic diversity.

The burden of undertreatment and non-treatment among patients with non-valvular atrial fibrillation and elevated stroke risk: a systematic review.

OBJECTIVE: Global treatment guidelines recommend treatment with oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and an elevated stroke risk. However, not all patients with NVAF and an elevated stroke risk receive guideline-recommended therapy. A literature review and synthesis of observational studies were undertaken to identify the body of evidence on untreated and undertreated NVAF and the association with clinical and economic outcomes. METHODS: An extensive search (1/2010-4/2020) of MEDLINE, the Cochrane Library, conference proceedings, and health technology assessments (HTAs) was conducted. Studies must have evaluated rates of nontreatment or undertreatment in NVAF. Nontreatment was defined as absence of OACs (but with possible antiplatelet treatment), while undertreatment was defined as treatment with only antiplatelet agents. RESULTS: Sixteen studies met our inclusion criteria. Rates of nontreatment for patients with elevated stroke risk ranged from 2.0-51.1%, while rates of undertreatment ranged from 10.0-45.1%. The clinical benefits of anticoagulation were reported in the evaluated studies with reductions in stroke and mortality outcomes observed among patients treated with anticoagulants compared to untreated or undertreated patients. Adverse events associated with all bleeding types (i.e. hemorrhagic stroke, major bleeding or gastrointestinal hemorrhaging) were found to be higher for warfarin patients compared to untreated patients in real-world practice. Healthcare resource utilization was found to be lower among patients highly-adherent to warfarin compared to untreated patients. CONCLUSIONS: Rates of nontreatment and undertreatment among NVAF patients remain high and are associated with preventable cardiovascular events and death. Strategies to increase rates of treatment may improve clinical outcomes.

The IMPact of untReated nOn-Valvular atrial fibrillation on short-tErm clinical and economic outcomes in the US Medicare population: the IMPROVE-AF model.

BACKGROUND: Despite treatment guidelines recommending the use of oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and moderate to high risk of stroke (CHA2DS2-VASc score ≥1), many patients remain untreated. A study conducted among Medicare beneficiaries with AF and a CHA2DS2-VASc score of ≥2 found that 51% of patients were not prescribed an OAC despite being eligible for treatment. When left untreated, NVAF poses an enormous burden to society, as stroke events are estimated to cost the US healthcare system about $34 billion each year in both direct medical costs and indirect productivity losses. This research explored the short-term clinical implications and budget impact (BI) of increasing OAC use among Medicare beneficiaries with NVAF. METHODS: A decision-analytic model was developed from the payer and societal perspectives to estimate the impact of increasing treatment rates among Medicare-eligible NVAF patients with a moderate-to-high risk of stroke over 1 year. Results of the model compared (1) a base case scenario using literature-derived rates of OAC use, and (2) a hypothetical scenario assuming an absolute 5% increase in overall OAC use. Clinical outcomes included the incremental annual number of ischemic stroke, hemorrhagic stroke, and gastrointestinal bleeding events, and stroke-related deaths. Economic outcomes included incremental annual and per-member per-month (PMPM) direct medical costs for the payer perspective and the incremental sum of annual direct medical and indirect costs from productivity loss and caregiver burden for the societal perspective. RESULTS: In total, 1.95 million Medicare patients with NVAF were estimated to be treated with OACs in the base case (3.8% of beneficiaries). In the hypothetical scenario analysis, nearly 200,000 more patients were treated resulting in 3,705 fewer ischemic strokes, 14 fewer gastrointestinal bleeds, 141 more hemorrhagic strokes, and 175 fewer deaths. The total incremental BI was $399.16 million ($0.65 PMPM) from the payer perspective and $377.10 million from the societal perspective due to indirect cost savings ($22.06 million). CONCLUSION: Our findings suggest that increased overall OAC use has a positive clinical benefit on the annual number of ischemic stroke events and deaths avoided in the Medicare population, while maintaining a modest increase in the overall BI to the Medicare system.

The evolving role of oral hormonal therapies and review of conjugated estrogens/bazedoxifene for the management of menopausal symptoms.

This review describes the evolving role of oral hormone therapy (HT) for treating menopausal symptoms and preventing osteoporosis, focusing on conjugated estrogens/bazedoxifene (CE/BZA). Estrogens alleviate hot flushes and prevent bone loss associated with menopause. In nonhysterectomized women, a progestin should be added to estrogens to reduce the risk of endometrial cancer. Use of HT declined since the Women's Health Initiative (WHI) studies showed that HT does not prevent coronary heart disease (CHD) and that conjugated estrogens/medroxyprogesterone acetate increased the risk of invasive breast cancer after nearly 5 years of use. However, re-analyses of the WHI data suggest that some risks (eg, CHD, all-cause mortality) may be reduced when HT is initiated in women <60 years of age and <10 years since menopause, compared with later. CE/BZA is the first menopausal HT without a progestogen for nonhysterectomized women. Instead, BZA, a selective estrogen receptor modulator, in combination with CE, protects against estrogenic effects on uterine and breast tissue. Data from 5 large, randomized clinical trials show that CE/BZA reduces hot flush frequency/severity, prevents bone loss, reduces bone turnover, improves the vaginal maturation index and ease of lubrication, and improves some measures of sleep and menopause-specific quality of life. In studies of up to 2 years, there was no increase in endometrial hyperplasia, vaginal bleeding, breast density, or breast pain/tenderness compared with placebo. Venous thromboembolism and stroke are risks of all estrogen-based therapies. The choice of HT should be individualized, with consideration of the risk/benefit profile and tolerability of therapy, as well as patient preferences.

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Pretreatment pattern of symptom expression in premenstrual dysphoric disorder.

BACKGROUND: Use of intermittent dosing strategies for the treatment of premenstrual dysphoric disorder (PMDD) highlights the need for detailed empirical data on the onset, duration and pattern of symptom expression in women suffering from PMDD. METHOD: Data were analyzed from 276 women who met DSM-IV criteria for PMDD and prospectively charted two menstrual cycles prior to commencing sertraline treatment. The presence and severity of PMDD symptoms were measured using the Daily Record of Severity of Problems (DRSP). RESULTS: The most frequent PMDD symptoms (moderate-to-severe for > or = 3 days) included anger/irritability (76%), anxiety/tension (71%), tired/lethargic (58%), and mood swings (58%). Mean DRSP scores peaked at day -2 (2 days prior to the onset of menses), but the within-patient day of onset of PMDD-level symptoms was highly variable, differing from cycle-to-cycle by > or = 4 days in 45% of women. Similarly, the within-patient duration of PMDD symptoms varied from cycle-to-cycle by 3 or more days in > or = 50% of women. Depending on the criteria used, 1 day after the onset of menstruation, 34-46% of women continued to report moderate to severe symptoms. LIMITATION: Women in this sample were recruited for participation in a treatment study, and the results may not generalize to women with PMDD in the community. CONCLUSION: The results of this analysis found significant within-patient variability in the time-to-onset and offset of PMDD symptoms, as well as their duration. The temporal pattern and high degree of within-patient variability across menstrual cycles of PMDD symptoms may have treatment implications.

Luteal phase treatment of premenstrual dysphoric disorder improves symptoms that continue into the postmenstrual phase.

BACKGROUND: Despite the proven efficacy of luteal phase medication dosing for women with premenstrual dysphoric disorder (PMDD), it is not known whether this approach adequately treats symptoms that linger into the first 2-3 days of the follicular phase, a time when up to one-third of women diagnosed with PMDD report residual symptoms. Furthermore, no previous study has explored whether abruptly stopping medication after 2 weeks of treatment is associated with discontinuation symptoms. METHODS: To evaluate the efficacy of luteal phase medication dosing, symptom data from the Daily Record of Severity of Problems (DRSP) during first few days of menses were compared from two studies with similar designs but different treatment strategies. The first study used continuous dosing of sertraline, 50-150 mg/day, throughout the menstrual cycle, while the second study used intermittent dosing with sertraline, 50-100 mg/day in the 14-16 days prior to onset of menses. To investigate whether abruptly stopping pills led to discontinuation symptoms, DRSP data for the first 5 days after the onset of menses were analyzed in the second (intermittent dosing) study. Symptom scores were compared for subjects who took either sertraline or placebo premenstrually and ceased taking pills at the onset of menses. RESULTS: The baseline (pretreatment) to on-treatment effect sizes were similar for continuous vs. luteal phase dosing on the first day of menses (0.73 vs. 0.89), second day of menses (0.40 vs. 0.55), and third day of menses (0.42 vs. 0.44), respectively. Subjects who abruptly discontinued sertraline had fewer symptoms indicative of withdrawal at Day 3 (p < 0.01) and no difference during Days 4-5 compared to subjects abruptly discontinuing placebo. CONCLUSION: Patients given active medication during the luteal phase demonstrate reductions in DRSP total scores into the first few days of menses regardless of whether active treatment was continuous throughout the menstrual cycle or was discontinued at the onset of menses. This analysis finds no support for discontinuation symptoms following abrupt cessation of sertraline after 2 weeks of treatment for two cycles.

Incidence of symptomatic gallstones after gastric bypass: is prophylactic treatment really necessary?

BACKGROUND: Because rapid weight loss after bariatric surgery increases gallstone formation, a 6-month treatment regimen with ursodiol has been recommended. Even prophylactic cholecystectomy at the time of gastric bypass in the absence of stones has been proposed. However, the incidence of symptomatic gallstones requiring cholecystectomy in untreated patients after gastric bypass has not yet been established. METHODS: The patients in our study were not treated with ursodiol after open Roux-en-Y gastric bypass. Additional inclusion criteria were no palpable gallstones at bypass, at least 16 months of follow-up after bypass, and continuous coverage by the same health insurance plan extending from the time of the operation to study completion, to track subsequent cholecystectomies by claims paid. RESULTS: A total of 100 females and 25 males met the study inclusion criteria. Follow-up extended from 16 to 48 months. Symptomatic gallstones requiring cholecystectomy developed in 10 patients, all females. Laparoscopic cholecystectomy was performed in 9 of these patients and open cholecystectomy was performed in the remaining patient, between 3 and 21 months after bypass. There were no serious complications from the stones or the cholecystectomy. CONCLUSIONS: Prophylactic cholecystectomy would have been unnecessary in 115 of the 125 patients in the study group. A 6-month course of ursodiol for all 125 patients, at a cost of 56,250 dollars, would have had to decrease the number of cholecystectomies from 10 to 3 to demonstrate a treatment effect (P < .05). Therefore, most newly formed gallstones after gastric bypass are likely asymptomatic, prophylactic cholecystectomy is not indicated, and ursodiol therapy may be better reserved for symptomatic patients who refuse surgery.

Improving clinical practice guidelines for practicing cardiologists.

Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as "Expert Consensus Statements" or "Task Force Committee Opinions," so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.

Sertraline versus fluoxetine in the treatment of major depression: a combined analysis of five double-blind comparator studies.

The aim of this study was to examine response and remission rates in outpatients treated with sertraline or fluoxetine who were suffering from two depression subtypes: anxious-depression and severe depression. Data were pooled from five double-blind studies comparing fluoxetine versus sertraline for the treatment of DSM-III-R or IV major depression. Clinical outcome was assessed using the Hamilton Depression Rating Scale (HAM-D) and the Clinical Global Impression-Improvement scale (CGI-I). One thousand and eighty-eight patients were randomized, with 654 (60%) meeting criteria for anxious depression and 212 (19%) meeting criteria for high severity depression. For the total sample, treatment response was similar for both sertraline and fluoxetine. In the high severity subgroup, the mean (+/-SD) HAM-D score at week 12 was 8.9+/-5.7 for sertraline and 10.8+/-6.9 for fluoxetine (P=0.07), and the mean (+/-SD) CGI-I score was 1.5+/-0.7 for sertraline and 2.0+/-1.1 for fluoxetine (P=0.005). CGI-I responder rates were 88% versus 71% (P=0.03) in the high severity subgroup, and 84% versus 79% (P=0.16) in the anxious-depression subgroup. Overall, sertraline and fluoxetine showed comparable antidepressant efficacy, although sertraline may offer an advantage in those patients with severe depression.

Food effect on the bioavailability of two distinct formulations of megestrol acetate oral suspension.

OBJECTIVE: Megestrol acetate oral suspension (MAOS) is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace (MAOS), and as a nanocrystal dispersion, Megace ES (MA-ES). Three studies were conducted to evaluate the pharmacokinetic properties of these formulations under fed and fasting conditions. METHODS: An open-label, crossover trial was conducted in 24 healthy males randomized to MA-ES 625 mg/5 mL given with a high-calorie, high-fat meal, or after an overnight fast. Blood samples were drawn at multiple time points and pharmacokinetic parameters were determined. Two separate, open-label reference studies evaluated MAOS 800 mg/20 mL in 40 fed or 40 fasting healthy male volunteers. RESULTS: In fasting MA-ES subjects, the average maximum concentration (C(max)) was 30% less than the fed C(max) value. For MAOS, fasting C(max) was 86% less than fed C(max). In fasting subjects, the area under the curve was 12,095 ng.h/mL for MA-ES, and 8,942 ng.h/mL for MAOS. In fed subjects, the absorption of the two formulations was comparable. CONCLUSION: Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects. MA-ES may be a preferred formulation of megestrol acetate when managing cachectic patients whose caloric intake is reduced.

Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies.

OBJECTIVE: Many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of premenstrual dysphoric disorder, but few studies have investigated the efficacy of SSRIs in the treatment of premenstrual syndrome (PMS). The objective of this study was to evaluate the safety and efficacy of sertraline in the treatment of moderate-to-severe PMS using 3 different dosing strategies: luteal phase (2 cycles), followed by continuous dosing throughout the month (1 cycle), followed by dosing begun at the first onset of PMS symptoms, or "symptom-onset" dosing (1 cycle). METHOD: 314 women with PMS from 22 U.S. sites were randomly assigned to fixed-dose treatment with sertraline (25 or 50 mg/day) or placebo for 4 menstrual cycles after a single-blind, placebo lead-in cycle. Assessments included the Daily Symptom Report (DSR), the Clinical Global Impressions-Severity of Illness and -Improvement scales, the Patient Global Evaluation scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, and the Social Adjustment Scale-Self Report. RESULTS: Intermittent luteal-phase dosing with low doses of sertraline (25 and 50 mg/day) produced significant improvement across 2 menstrual cycles, based on total DSR scores, compared with placebo. Continuous and symptom-onset dosing were also effective in treating PMS symptoms, particularly at the lower dose of 25 mg/day. CONCLUSIONS: The results of the current study suggest that low doses of sertraline may be a safe, effective, and well-tolerated treatment for moderate-to-severe PMS.

ACCF/ASNC appropriateness criteria for single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI): a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group and the American Society of Nuclear Cardiology endorsed by the American Heart Association.

Under the auspices of the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC), an appropriateness review was conducted for radionuclide cardiovascular imaging (RNI), specifically gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The review assessed the risks and benefits of the imaging test for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid range (4 to 6) implies that the test may be generally acceptable and may be a reasonable approach for the indication. The indications for this review were primarily drawn from existing clinical practice guidelines and modified based on discussion by the ACCF Appropriateness Criteria Working Group and the Technical Panel members who rated the indications. The method for this review was based on the RAND/UCLA approach for evaluating appropriateness, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first- and second-round ratings of 52 clinical indications. The ratings were done by a Technical Panel with diverse membership, including nuclear cardiologists, referring physicians (including an echocardiographer), health services researchers, and a payer (chief medical officer). These results are expected to have a significant impact on physician decision making and performance, reimbursement policy, and future research directions. Periodic assessment and updating of criteria will be undertaken as needed.