A systematic literature review of the clinical and health economic burden of schizophrenia in privately insured patients in the United States.

PURPOSE: The aim of this study was to conduct a systematic literature review on the burden of schizophrenia in privately insured US patients. MATERIALS AND METHODS: A systematic literature review of English language peer-reviewed journal articles of observational studies published from 2006 to 2016 was conducted using EMBASE/MEDLINE databases. Abstracts covering substantial numbers of patients with schizophrenia or schizoaffective disorder (i.e., N ≥ 100) were included for full-text review. Articles that did not clearly specify private insurance types were excluded. RESULTS: A total of 25 studies were reviewed; 10 included only privately insured patients; and 15 included a mix of different types of insurance. The review of the clinical burden of schizophrenia revealed the following: compared to patients with no mental disorders, those with schizophrenia had significantly increased odds of systemic disorders and both alcohol and substance abuse. Antipsychotic (AP) adherence was low, ranging from 31.5% to 68.7%. The medication possession ratio for AP adherence ranged from 0.22 to 0.73. The review of the health economic burden of schizophrenia revealed the following: patients with a recent (vs. chronic) diagnosis of schizophrenia had significantly higher frequencies of emergency department visits and hospitalizations and greater length of stay (LOS) and total annual per-capita costs. Mean all-cause hospitalizations and LOS decreased significantly after (vs. before) initiating long-acting injectable APs (LAIs). Patients also had significantly decreased mean all-cause, and schizophrenia-related, hospitalization costs after initiating LAIs. Total direct per-capita costs of care (but not pharmacy costs) for patients who were nonadherent to their oral APs within the first 90 days of their index event were significantly higher (vs. early adherent patients). Despite these potential benefits, only 0.25%-13.1% of patients were treated with LAIs across all studies. CONCLUSION: Privately insured US patients with schizophrenia experience a substantial clinical and health economic burden related to comorbidities, acute care needs, nonadherence, and polypharmacy and have relatively low use of LAIs. Further study is warranted to understand prescribing patterns and clinical policies related to this patient population.

Total and low-density lipoprotein cholesterol in high-risk patients treated with atorvastatin monotherapy in the United Kingdom: analysis of a primary-care database.

OBJECTIVE: British clinical guidelines recommend statins as first-line lipid-modifying treatment (LMT) for patients at high risk of cardiovascular disease (CVD). We undertook an observational study to assess total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-risk patients who were treated with atorvastatin monotherapy by UK general practitioners. METHODS: This retrospective database study included patients with a prescription for atorvastatin monotherapy between November 30, 2008, and November 30, 2011, with the index date defined as the first atorvastatin prescription during this period. Eligible high-risk patients with evidence of coronary heart disease (CHD), atherosclerotic vascular disease (AVD), diabetes mellitus (DM), or familial hypercholesterolemia (FH) were required to have ≥1 TC and LDL-C measurement between 3 and 12 months after the index date, and continuous enrollment 1 year before and 1 year after the index date. Cholesterol levels were assessed using the National Institute for Health and Care Excellence (NICE) guidelines: TC <4.0 mmol/L or LDL-C <2.0 mmol/L. RESULTS: Of 2999 high-risk patients (60.2% men; mean [SD] age = 67.9 [10.6] years) meeting selection criteria, 23.9% 28.2%, 36.2%, and 11.6% received prescriptions for atorvastatin 10, 20, 40, and 80 mg, respectively (percentages do not sum to 100 because of rounding). Across all doses, the mean (SD) follow-up TC was 4.08 (0.80) mmol/L and LDL-C 2.08 (0.65) mmol/L. A large proportion of patients (88.8%) had TC < 5.0 mmol/L. However, only 45.8% had TC < 4.0 mmol/L, and 46.5% had LDL-C < 2.0 mmol/L. Although a larger proportion of patients with CHD/AVD + DM reached guideline-recommended lipid levels, only 63.7% of such patients had TC < 4.0 or LDL-C < 2.0 mmol/L, which are the current targets for this subgroup as recommended by NICE. CONCLUSIONS: Less than half of UK high-CVD-risk patients receiving atorvastatin monotherapy achieved guideline-recommended treatment targets for TC, and less than two-thirds of patients with CHD/AVD + DM had values below TC (4.0 mmol/L) or LDL-C (2.0 mmol/L) targets. More effective lipid-lowering strategies may be warranted to optimize cholesterol lowering and target attainment in high-risk patients. Limitations of this study include its retrospective, observational nature.

Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied. OBJECTIVE: To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults. METHODS: Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale. RESULTS: Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 - 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 -0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each). CONCLUSIONS: No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. TRIAL REGISTRATION (BASE STUDY): ClinicalTrials.gov identifier: NCT00190957.

Optimizing treatment outcomes with phosphodiesterase type 5 inhibitors for erectile dysfunction: opening windows to enhanced sexual function and overall health.

PURPOSE: Phosphodiesterase type 5 (PDE5) inhibitors have proved to be efficacious, safe, and well tolerated, in clinical trials and practice, for men with erectile dysfunction (ED). However, many patients are not satisfied with treatment and discontinue it prematurely. This review discusses evidence-based strategies that nurse practitioners (NPs) can use to improve diagnosis of ED, optimize patient outcomes, and identify opportunities to detect other potentially serious comorbid conditions. DATA SOURCES: This article was based on a previously published review, which involved a PubMed-MEDLINE search of the clinical literature from January 1, 1998 (year of sildenafil's approval in many markets), through August 30, 2008 (date of search). CONCLUSIONS: Strategies to optimize responses to PDE5 therapy are summarized by the mnemonic "EPOCH": Evaluating and educating to ensure realistic expectations of therapy; Prescribing a treatment individualized to the couple's needs and preferences; Optimizing drug dose/regimen and revisiting key educational messages at follow-up visits; Controlling comorbidities via lifestyle counseling, medications, and/or referrals; and Helping patients and their partners to seek other forms of therapy if they have decided not to use a PDE5 inhibitor. IMPLICATIONS FOR PRACTICE: The "EPOCH" mnemonic may remind NPs of steps to optimize treatment outcomes with PDE5 inhibitors.

Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies.

BACKGROUND: The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD. METHODS: Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. RESULTS: The median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (p = .33). CONCLUSIONS: Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00191633, NCT00216918, NCT00191880.

Sexual satisfaction in men with erectile dysfunction: correlates and potential predictors.

INTRODUCTION: Sexual satisfaction is an important treatment objective for men with erectile dysfunction (ED). AIMS: To evaluate potential associations between International Index of Erectile Function (IIEF) satisfaction at study endpoint and a range of baseline, on-treatment, and endpoint variables. METHODS: An exploratory analysis was conducted involving 3,935 subjects with ED randomized to on-demand tadalafil (N = 2,824) or placebo (N = 1,111) in randomized, controlled trials across 28 countries. Patients achieving scores > or =16 on IIEF questions 7, 8, 13, and 14 at study endpoint were operationally defined as satisfied (vs. <16, not satisfied). Multivariate logistic regression and other analyses were conducted to ascertain correlates and potential predictors of improvements in the IIEF-erectile function domain (IIEF-EF). MAIN OUTCOME MEASURES: Satisfaction on the IIEF at study endpoint, on-treatment improvements in IIEF-EF, and endpoint sexual frequency. RESULTS: Patients who were satisfied with sexual function were on average younger and had less severe ED, a shorter history of the condition, and no history of vascular disorders, hypertension, or diabetes mellitus/insulin use at baseline (P < 0.01 vs. not satisfied for each). Satisfied patients were also more likely to experience a > or =4-point increase on the IIEF-EF domain on treatment (adjusted odds ratio [OR] = 22.4; 95% CI = 17.6-28.5; P < 0.0001) or IIEF-EF > or =26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6-50.2; P < 0.0001). Satisfaction emerged as a strong correlate of a > or =4-point increase in the IIEF-EF on treatment; however, as a correlate of endpoint sexual frequency, baseline sexual frequency was stronger than endpoint satisfaction. CONCLUSIONS: Satisfaction is associated with certain baseline, on-treatment, and endpoint variables in ED patients. Further studies are needed to confirm these preliminary findings and explore their meaning for female partners.

Effects of modifying triglycerides and triglyceride-rich lipoproteins on cardiovascular outcomes.

Elevated levels of triglycerides (and triglyceride-rich lipoproteins) are increasingly being recognized as treatment targets to lower cardiovascular risk in certain patient subgroups, including individuals receiving HMG-CoA reductase inhibitors (statins). Evidence suggests that these agents reduce the risk of coronary events more markedly in patients with elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C). Further, intensive long-term statin therapy that reduces both low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL and triglycerides to <150 mg/dL results in a decreased risk of cardiovascular events compared with more moderate statin treatment. Long-term therapy with fibric-acid derivatives, which lower triglycerides and raise HDL-C, appears to reduce mortality in patients with elevated triglycerides and/or those experiencing the most marked reductions in triglycerides on therapy. However, randomized clinical trials involving fibrates have not shown consistent benefit. Niacin (nicotinic acid), which is the most effective available medication for raising HDL-C and also lowers triglycerides, has not been as extensively studied as fibrates in long-term randomized controlled trials. Initial reports (eg, Coronary Drug Project) demonstrated a reduction in coronary disease but not total mortality in patients randomized to niacin. However, a 15-year follow-up demonstrated that all-cause mortality was significantly reduced in those initially randomized to niacin. At the pathophysiologic level, elevated triglycerides and triglyceride-rich lipoproteins are recognized as potential factors in driving atherosclerotic progression, particularly in mild-to-moderate lesions. Elevated triglycerides also constitute a plausible therapeutic target in certain patients with coronary heart disease (and/or insulin resistance) but without profound LDL-C elevations. The foregoing and other evidence has led consensus panels to lower the upper limit for "normal" triglycerides to 150 mg/dL. Adequately powered randomized controlled trials that specifically assess the effects of lowering triglycerides and raising HDL-C, and trials that target individuals with high triglycerides and low HDL-C, may provide data for recommending specific treatment targets for triglycerides and HDL-C, as well as effective and well-tolerated therapies to achieve these goals.

Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?

Type 2 diabetes mellitus is associated with progressive decreases in pancreatic beta-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet alpha- and beta-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve beta-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.

Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia.

BACKGROUND: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters. OBJECTIVES: To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels. METHODS: A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10 mg, simvastatin (10-80 mg), and atorvastatin (10-80 mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipo protein [LDL-C] = 145-250 mg/dL; triglycerides < or = 350 mg/dL; N = 975) but without a recent (< or = 6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus. RESULTS: Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p < 0.001), whereas statins significantly lowered desmo sterol and lathosterol levels (p < 0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p < 0.001). CONCLUSIONS: The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe-statin) doses and circulating non-cholesterol levels.

Effects of a global risk educational tool on primary coronary prevention: the Atherosclerosis Assessment Via Total Risk (AVIATOR) study.

OBJECTIVE: The use of Framingham equations to determine 10-year absolute coronary risk ('global risk') represents an accepted strategy to target coronary prevention measures and enhance clinical outcomes. The aim of this study was to determine the effects of providing global risk scores to physicians on the prescription of lipid-lowering therapy for patients at increased coronary risk. RESEARCH DESIGN AND METHODS: This prospective, randomized controlled trial enrolled 368 primary-care patients without a history of coronary heart disease and not on therapy with a hydroxymethylglutaryl coenzyme A reductase inhibitor (i.e. statin). The study was conducted in the general medical clinics of an academic US teaching hospital. In the intervention group (n = 186) patients' charts were reviewed, 10-year absolute coronary risk computed, and this information conveyed via a simple educational tool appended to charts. In the control group (n = 182), charts were accompanied by a form with general information on coronary prevention goals and strategies. MAIN OUTCOME MEASURE: The primary endpoint was the proportion of high-risk patients receiving a new statin prescription. Secondary and tertiary endpoints included (1) the proportion of moderate-risk patients receiving a statin prescription; and (2) the proportion of patients in the whole cohort who had other coronary prevention measures recommended. RESULTS: There was no significant difference in statin prescription to high-risk individuals in the intervention group (40.0%) compared with the control group (37.9%; p = 0.86). Moderate-risk individuals who were not eligible for treatment according to the National Cholesterol Education Program Adult Treatment Panel II guidelines were more likely to receive a statin prescription in the intervention group versus the control group (28.8% vs. 12.5%. p = 0.036) CONCLUSIONS: Although a simple global risk educational tool did not improve the targeting of statin therapy to patients at high absolute coronary risk, it may be of benefit in targeting moderate-risk individuals who do not have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. Future research should evaluate the effects of physicians performing their own Framingham risk calculations on statin prescribing and on cholesterol goal attainment.