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Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians, policymakers, and researchers. To describe the epidemiology of gastrointestinal and liver diseases in the United States using data from privately and publicly held databases. We collected data from the National Center for Health Statistics, the National Ambulatory Medical Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease incidence from these databases, and extracted data specific to gastrointestinal diseases. Because of the high costs associated with medications used to treat gastrointestinal diseases, we also include in this year's report a special section on pharmacoepidemiology and pharmacoeconomics. Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis following. Americans spend in excess of US dollars 10 billion/yr on proton pump inhibitors (PPIs), and two of the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent changes, likely reflecting both new drug entries into the field, as well as drug marketing. The number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs used for gastrointestinal diseases are among the top 200 generic drugs used in the United States. Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and health-care expenditures of the U.S. population.

To examine patterns of generic escitalopram initiation and substitution among Medicare beneficiaries. This retrospective new user cohort used a 5% random sample of 2013-2015 Medicare administrative claims data. Fee-for-service Medicare beneficiaries continuously enrolled in Parts A, B, and D during a 6-month washout period prior to their initial generic or brand oral escitalopram prescriptions were included (n = 12,351). The primary outcomes were generic escitalopram treatment initiation, and among brand escitalopram initiators, generic substitution within 12 months. Patient demographics, health service utilization, and prescription level factors were measured and assessed. Among all escitalopram initiators, about 88.2% Medicare beneficiaries initiated generic escitalopram. Beneficiaries who were younger age, male, residing in non-Northeast regions or urban area, in the Part D plan deductible benefit phase, and filling prescriptions at community/retail pharmacies were more likely to initiate generic treatment. Among brand escitalopram initiators (n = 1,464), about 20.7% switched to generic escitalopram, 31.2% switched to another alternative antidepressant, 25.1% discontinued treatment, and 8.7% were lost to follow up or passed away within 12 months after brand initiation. Factors associated with generic escitalopram substitution included region (Midwest vs. Northeast, adjusted hazard ratio (HR) = 1.46, 95% CI = 1.04-2.05), pre-index hospitalization (HR = 1.31; 95% CI = 1.16-1.48) and lower escitalopram average daily dosage (HR = 0.97; 95% CI = 0.95-0.99). In 2013-2015, almost 90% Medicare beneficiaries initiated generic escitalopram treatment. Among brand escitalopram initiators, about 1 in 5 patients switched to generic escitalopram within 1 year, as compared to 1 in 4 or 1 in 3 who discontinued current or switched to alternative treatment, respectively. Medicare beneficiary's geographic region was independently associated with generic escitalopram initiation and substitution. Findings from this study not only provide up-to-date evidence in generic escitalopram use patterns among Medicare population, but also can guide educational and practice interventions to further increase generic escitalopram use.

Reviews have compared the efficacy and tolerability of newer second-generation antidepressants with those of placebo or older treatments, but comparative evidence for use of second-generation antidepressants to treat major depressive disorder has not been evaluated. To systematically evaluate comparative data on the efficacy, effectiveness, and tolerability of commonly prescribed second-generation antidepressants (selective serotonin reuptake inhibitors, bupropion, duloxetine, mirtazapine, and venlafaxine) in the treatment of major depressive disorder. MEDLINE, EMBASE, and PsychLit; the Cochrane Library; and the International Pharmaceutical Abstracts were searched from January 1980 through February 2005 for reviews; randomized, controlled trials; meta-analyses; and observational studies. The authors reviewed 46 head-to-head randomized, controlled trials comparing one second-generation antidepressant with another. Twenty-four observational studies and placebo-controlled trials were also included for assessment of safety and tolerability. Two researchers independently reviewed titles and abstracts. Trained reviewers abstracted data from each study and assigned an initial quality rating. A second reviewer verified the data extraction and quality rating. According to fair to good evidence, the second-generation antidepressants that were compared had only minimal differences in efficacy, and 88% of comparative efficacy studies reported no statistically significant difference in any outcome measure at the end of the study. One effectiveness trial rated good and 2 effectiveness trials rated fair reported no statistically significant differences in primary outcome measures for compared drugs. Meta-analyses showed a modest but statistically significant additional treatment effect for sertraline and venlafaxine compared with fluoxetine. About 96% of comparative trials were sponsored by or had at least 1 author affiliated with a pharmaceutical company; the remaining trials did not report funding sources. Adverse event profiles differed among drugs; however, the degree and quality of adverse event assessment varied and only 13% of trials used a standardized scale to assess adverse events. Quantitative analyses could not be done for many drug comparisons because the quantity and quality of the evidence were inadequate. Most published evidence was from trials sponsored by pharmaceutical companies, and publication bias may have occurred. Overall, second-generation antidepressants probably do not differ substantially for treatment of major depressive disorder. Choosing the agent that is most appropriate for a given patient is difficult.

This study compares the risks of arrhythmia among patients with depression receiving selective serotonin reuptake inhibitors (SSRIs) and those receiving other classes of antidepressants and among patients with depression receiving citalopram-escitalopram and those receiving other SSRIs. This retrospective cohort study used data from the 2000–2011 National Health Insurance Research Database in Taiwan. Patients with depression who were new antidepressant users were included in the study sample. Propensity score matching was used to balance the covariates between the comparison groups. Crude incidence rates were generated by Poisson regressions, and Cox proportional hazards regression models were used to assess the rates of arrhythmia among SSRI users and nonusers of SSRI antidepressants as well as between citalopram-escitalopram users and users of other SSRIs. Neither SSRI (hazard ratio [HR] = 0.95; 95% CI, 0.83–1.08) nor citalopram-escitalopram (HR = 1.20; 95% CI, 0.95–1.51) exposure was associated with a risk of arrhythmia compared with other, newer non-SSRI antidepressants or noncitalopram SSRIs. An increase in mortality was, however, observed among citalopram-escitalopram users (HR = 1.21; 95% CI, 1.08–1.31). Citalopram, escitalopram, and other SSRIs were not associated with an elevated risk of arrhythmia compared with each other or with non-SSRI antidepressants. Nevertheless, citalopram and escitalopram were associated with an increase in mortality risk compared with other SSRIs and deserve further investigation.

Antihypertensive drugs are prescribed to patients with chronic kidney disease (CKD) for their cardioprotective and renoprotective effects. Nationally representative information on the use of antihypertensive drugs among CKD patients is limited. The purpose of this study was to assess the utilization patterns of antihypertensive drugs among the CKD population (stages I–IV) in the United States. We conducted a retrospective cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) panels from 2005–2006, 2007–2008, and 2009–2010. The estimated glomerular filtration rate was calculated and kidney damage was assessed to identify participants with CKD. The demographic and clinical characteristics of the participants with CKD were reported, as were the antihypertensive drugs they used. A total weighted sample of 116,231,361 participants representative of the CKD population in the United States (stages I–IV) was identified. Less than one half of the participants with CKD in the NHANES were using antihypertensive drugs. β-blockers were the most commonly used and angiotensin II receptor blockers were the least used antihypertensive agents among participants with CKD. Age (≥70 years), awareness of hypertension or diabetes, and higher stage of CKD were associated with an increased likelihood of antihypertensive drug use among participants with CKD. The results of our analyses suggest that antihypertensive drugs are underused in the CKD population, and the use of preferred agents (ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) is low. Efforts should be directed toward emphasizing the importance of using antihypertensive drugs in the CKD population.

Objectives: The aims of this study were to compare all-cause total health care costs and diabetes mellitus (DM)-specific health care costs between patients who were adherent or nonadherent to monotherapy with metformin, pioglitazone, or a sulfonylurea and to examine whether cost differences varied among patients using these oral antidiabetic drugs. Methods: This was a retrospective cohort study using data from the MEDSTAT MarketScan Research Databases. Patients aged 18 to 90 years who were continuously insured between 2003 and 2005 and had ≥2 outpatient claims or ≥1 inpatient claim with a diagnosis of DM ( International Classification of Diseases, Ninth Revision, Clinical Modification code 250.xx) in 2003 were eligible for the study. To be part of the final sample, patients had to fill ≥2 prescriptions for metformin, pioglitazone, or a sulfonylurea during 2003, including ≥1 prescription during the last 3 months of the year. Patients were not eligible if they were taking polytherapy or a combination drug. All eligible patients were followed in 2004 and 2005. Adherence was calculated for each year using a medication possession ratio, and was dichotomized at ≥80% as either adherent or nonadherent. Annual all-cause health care costs and diabetes-specific costs were estimated using generalized linear models, adjusting for demographic characteristics, insurance, and comorbid conditions. Results: A total of 108,592 patients who met the inclusion criteria were identified. Their mean age was 63 years; 49.8% (54,037/108,592) were women. More pioglitazone users resided in the north-central or south regions (81.3% [9364/11,520]) compared with metformin (62.4% [32,550/52,156]) or sulfonylurea (62.6% [28,105/44,916]) users ( P < 0.001). Mean comorbidity scores were higher in the sulfonylurea (1.78) and pioglitazone (1.69) group than in the metformin group (1.45) ( P < 0.001). Mean adherence ranged from 61.3% to 73.8% during the 2 years of follow-up. After adjustment, all-cause health care costs were $12,412 annually among adherent patients and $13,258 among nonadherent patients (difference, $846 [95% CI, $747 to $945]). Diabetes-related health care costs were $2230 annually among adherent patients and $2284 among nonadherent patients (difference, $55 [95% CI, $33 to $77]). In specific monotherapy groups, adjusted annual all-cause health care costs were $336 higher (95% CI, $216 to $456) for nonadherent metformin users, $1140 higher (95% CI, $793 to $1486) for nonadherent pioglitazone users, and $1509 higher (95% CI, $1339 to $1679) for nonadherent sulfonylurea users compared with adherent users. Compared with metformin users, sulfonylurea and pioglitazone users had greater adherence-related differences in all-cause health care costs ( P < 0.05). There was no significant difference in diabetes-specific total costs between nonadherent and adherent patients taking metformin (difference, $6; 95% CI, −$31 to $20). Patients who were nonadherent to sulfonylureas had $271 higher (95% CI, $235 to $307) diabetes-specific costs per year than patients who were adherent to sulfonylureas. Patients who were nonadherent to pioglitazone had $433 lower (95% CI, −$516 to −$350) diabetes-specific costs per year than patients who were adherent to pioglitazone. Conclusions: Adherence with metformin, pioglitazone, or a sulfonylurea was associated with overall cost reductions in the patients studied, but these cost reductions varied by monotherapy. Adherence to sulfonylureas or pioglitazone was associated with greater total cost reductions than was adherence to metformin. Health systems that commit resources to improving interventions may be able to achieve a return on investment if adherence to oral antidiabetic agents can be improved.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension. Methods We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy. Results Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure (95% CI, 0.7 to 3.3). Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen (95% CI, 0.5 to 4.6), and a 5 mmHg increase compared to celecoxib (95% CI, 0.4 to 10). The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant. Conclusion Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible.

Background The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. Objective To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Methods Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Results Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Conclusion Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA.

Background Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGADs) that are commonly used to treat the condition. Evidence indicates under-reporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life. Objectives Our objective was to systematically assess the harms of SD associated with SGADs in adult patients with MDD by drug type. Methods We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least 6 weeks’ duration and observational studies with at least 1,000 participants. Study Selection Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk-of-bias ratings. Analyses Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies. Results/Synthesis Data from 63 studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGADs were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs. However, credible intervals were wide and included differences that would be considered clinically relevant. We observed three main patterns: bupropion had a statistically significantly lower risk of SD than some other SGADs, and both escitalopram and paroxetine showed a statistically significantly higher risk of SD than some other SGADs. We found reporting of harms related to SD inconsistent and insufficient in some trials. Limitations Most trials were conducted in highly selected populations. Search was restricted to English-language only. Conclusion and Implications Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients’ preferences before initiating antidepressant therapy.