Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

High-Intensity Interval Training is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Dialysis and plasmapheresis for schizophrenia: a systematic review.

Increasing evidence suggests that circulating factors and immune dysfunction may contribute to the pathogenesis of schizophrenia. In particular, proinflammatory cytokines, complement and autoantibodies against CNS epitopes have recently been associated with psychosis. Related concepts in previous decades led to several clinical trials of dialysis and plasmapheresis as treatments for schizophrenia. These trials may have relevance for the current understanding of schizophrenia. We aimed to identify whether dialysis or plasmapheresis are beneficial interventions in schizophrenia. We conducted a systematic search in major electronic databases for high-quality studies (double-blinded randomised trials with sham controls) applying either haemodialysis or plasmapheresis as an intervention in patients with schizophrenia, published in English from the start of records until September 2018. We found nine studies meeting inclusion criteria, reporting on 105 patients in total who received either sham or active intervention. One out of eight studies reported a beneficial effect of haemodialysis on schizophrenia, one a detrimental effect and six no effect. The sole trial of plasmapheresis found it to be ineffective. Adverse events were reported in 23% of patients. Studies were at unclear or high risk of bias. It is unlikely that haemodialysis is a beneficial treatment in schizophrenia, although the studies were of small size and could not consider potential subgroups. Plasmapheresis was only addressed by one study and warrants further exploration as a treatment modality in schizophrenia.

Testing the 'seizure scaffold': What can experimental simulation tell us about functional seizures?

INTRODUCTION: It has been suggested for over 100 years that patterns of neurological symptoms and signs in functional neurological disorders may be shaped at a neural level by underlying ideas or preconceptions how neurological symptoms present. This study used experimental simulation to probe ideas about seizures in healthy volunteers, with a view to compare with features commonly observed in functional and epileptic seizure disorders. METHODS: Sixty healthy volunteers were instructed to simulate an epileptic seizure. The episodes were video-recorded and assessed by three qualified markers for the presence of clinical features commonly observed in functional seizures (FS), epileptic seizures, and syncope. RESULTS: Simulated seizures were hyperkinetic (83%), hypokinetic (7%), or staring (10%). Fifty-two percent had their eyes open and 45% eyes closed. Tremor was observed in 70%, while clonic jerking was only present in 17%. The majority of volunteers maintained a normal or floppy body posture. Head shaking side-to-side was observed in 38%, while guttural cries, stertorous breathing, tearfulness, and hyperventilation were absent in all volunteers. DISCUSSION: Our results suggest that simulated seizures not only resemble FS more closely than epileptic seizures but also show some important differences. Subjective seizure experiences in people with FS, not captured by this experimental simulation, remain a core determinant of semiology.

High-intensity Interval Training for the Management of Nonalcoholic Steatohepatitis: Participant Experiences and Perspectives.

Background and Aims: High-intensity interval training (HIIT) is a therapeutic option for people with nonalcoholic steatohepatitis (NASH). However, the perspectives and experiences of HIIT for people with NASH are unknown, limiting translation of research. We explored the experiences and perspectives of both professionally supervised and self-directed HIIT in people with NASH and evaluated participant-reported knowledge, barriers, and enablers to commencing and sustaining HIIT. Methods: Twelve participants with NASH underwent 12 weeks of supervised HIIT (3 days/week, 4×4 minutes at 85-95% maximal heart rate, interspersed with 3 minutes active recovery), followed by 12-weeks of self-directed (unsupervised) HIIT. One-on-one, semistructured participant interviews were conducted by exercise staff prior to HIIT and following both supervised and self-directed HIIT to explore prior knowledge, barriers, enablers, and outcomes at each stage. Interviews were audio-recorded, transcribed, coded, and thematically analyzed by two independent researchers. Results: Four dominant themes were identified: (1) no awareness of/experience with HIIT and ambivalence about exercise capabilities; (2) multiple medical and social barriers to commencing and continuing HIIT; (3) exercise specialist support was a highly valued enabler, and (4) HIIT was enjoyed and provided holistic benefits. Conclusions: People with NASH may lack knowledge of and confidence for HIIT, and experience multiple complex barriers to commencing and continuing HIIT. Exercise specialist support is a key enabler to sustained engagement. These factors need to be addressed in future clinical programs to augment the uptake and long-term sustainability of HIIT by people with NASH so they can experience the range of related benefits.

Structured Observations of Child Behaviors during a Mastery-Motivational Climate Motor Skill Intervention: An Exploratory Study.

This exploratory study aimed to quantify children's engagement behaviors during a mastery-motivational climate intervention. We also completed an exploratory factor analysis to elucidate if child engagement changed across intervention sessions. METHOD: 35 children (17 boys; 18 girls) completed a 10-week mastery-motivational climate motor skill intervention. Engagement was operationalized as the time children were appropriately involved in the intervention and was assessed using momentary time sampling during the motor skill practice portion of the intervention. RESULTS: Overall, children were engaged 36% of the motor skills practice time (37% for boys; 36% for girls). Children who initially had below-average skills engaged for 36% (36% for boys; 35% for girls) of the motor skills practice time, and children who were average or above-average at the start of the intervention engaged in skill practice for 39% (39% for boys; 36% for girls). Differences in engagement in skill type (e.g., locomotor vs. ball skills) and trends over time were observed. CONCLUSION: These findings support that children engage in mastery-motivation climates, but the amount of participation may be influenced by individual factors of sex and initial skill level.

Effects of fitness and fatness on age-related arterial stiffening in people with type 2 diabetes.

People with type 2 diabetes (T2D) are at a greater risk of cardiovascular disease than the general population. Both non-modifiable (age) and modifiable (low aerobic fitness, high body fatness) factors are separately predictive of cardiovascular risk, although they often occur concomitantly. This study aimed to examine the (1) association between age and arterial stiffness, a subclinical marker of cardiovascular risk; and (2) effects of body fatness and aerobic fitness on age-related increases in arterial stiffness in people with T2D. Data from 64 individuals with T2D (age 59.8 ± 8.7 years, 40% female, HbA1c 8.4 ± 1.6%) were included in this cross-sectional analysis. Carotid-femoral pulse wave velocity (cfPWV) was used to quantify arterial stiffness. Aerobic fitness (relative V̇O2peak ) was determined via indirect calorimetry during maximal exercise testing. Central body fatness was determined using waist circumference. Data were analysed using hierarchical multiple regressions. After adjustment for sex and duration of T2D, each one standard deviation (SD) increase in age (8.68 years) was associated with a 0.63 m·s-1 increase in cfPWV (ß = 0.416, p = 0.001). Following adjustment for aerobic fitness and body fatness, the standardized ß was unchanged (0.417). A one SD increase in waist circumference (13.9 cm) and relative V̇O2peak (5.3 ml·kg-1 ·min-1 ) were associated with a similar magnitude of difference in cfPWV (0.47 m·s-1 and -0.44 m·s-1 , respectively). Therefore, age is a significant correlate of increased arterial stiffness in T2D, with higher aerobic fitness attenuating, and higher body fatness exacerbating, this increase. Interventions aimed at improving cardiovascular outcomes in people with T2D should target both increased aerobic fitness and reduced body fatness.

Personal Activity Intelligence e-Health Program in People with Type 2 Diabetes: A Pilot Randomized Controlled Trial.

INTRODUCTION: Innovative strategies are needed to enable people with type 2 diabetes (T2D) to self-manage physical activity (PA). Personal Activity Intelligence (PAI) is a new metric that uses the heart rate response to PA to inform the user as to whether they are doing enough PA to reduce the risk of premature mortality. The PAI score reflects PA over the previous 7 d with the goal to maintain a score ≥100. The aim of this study was to investigate the feasibility, acceptability, and efficacy of the PAI e-Health Program in people with T2D. METHODS: Thirty participants with T2D who were not meeting PA guidelines were randomly assigned to 12 wk of either 1) PAI e-Health Program or 2) PA attention control. The PAI e-Health Program consisted of receiving a wrist-worn heart rate monitor and an app with the PAI metric, and attending 4 × 2 h·wk-1 sessions of exercise and counseling. Feasibility and acceptability of the program were evaluated by achievement of a PAI score ≥100 and participant feedback. Efficacy was determined from changes in glycemic control, cardiorespiratory fitness, exercise capacity (time-on-test), body composition, sleep time, and health-related quality of life. RESULTS: Program participants in the PAI e-Health Program had a mean ± SD PAI score of 119.7 ± 60.6 and achieved ≥100 PAI on 56.4% of the days. The majority of participants (80%) intended to continue to use PAI monitoring. Compared with control, the PAI group significantly improved their exercise capacity (mean difference, 95% confidence interval) (63 s, 17.9-108.0 s), sleep time (67.2 min, 7.2-127.1 min), total percent body fat (-1.3%, -2.6% to -0.1%), and gynoid fat percent (-1.5%, -2.6 to -0.5). CONCLUSIONS: The PAI e-Health Program is feasible, acceptable, and efficacious in people with T2D.

Gender differences in self-reported symptom awareness and perceived ability to manage therapy with disease-modifying medication among commercially insured multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic, neurodegenerative inflammatory disease that affects approximately 400,000 Americans, the majority of whom are female. Although MS prevalence is higher among females, males are more likely to have a more progressive clinical course. For both genders, use of disease-modifying medications (DMMs) in the clinical management of MS is pivotal in altering the natural course and diminishing progressive disability over time. OBJECTIVES: To evaluate gender differences in self-reported symptom awareness and perceived ability to manage therapy among MS patients taking a DMM. METHODS: During February 2008, a self-administered, 42-item survey was mailed to 4,700 commercially insured patients taking a DMM to treat MS. Survey items measured self-reported clinical characteristics, symptom awareness, and perceived ability to manage therapy. Bivariate analyses assessed associations of gender with other predictor and outcome variables, including demographic characteristics, clinical disease characteristics, specific DMM used at the time of the survey, self-reported symptom awareness, and perceived ability to manage therapy. Logistic regression analyses further assessed the associations of gender with symptom awareness and perceived ability to manage MS after adjustment for relevant covariates (age at diagnosis, educational level, income, current DMM, type of pharmacy where drug was dispensed, frequency of flare-ups, and clinical course of disease). RESULTS: The response rate was 44.1% (n = 2,074). Of the 2,022 respondents with useable surveys, 80.6% were female; 82.3% had relapsing remitting MS; and 83.1% were taking one of the most commonly used DMMs (intramuscular interferon beta-1a 33.4%, subcutaneous interferon beta-1a 15.9%, and glatiramer acetate 33.8%). Compared with female patients, males were older and a greater proportion had a more progressive clinical course of disease. In multivariate models, female patients were more likely than males to report recognition of a relapse/exacerbation (odds ratio [OR] = 1.37, 95% CI = 1.03-1.82) and to report knowing what to do when experiencing a relapse/exacerbation (OR = 1.34, 95% CI = 1.01- 1.77) or if they missed a dose of medication (OR = 1.78, 95% CI = 1.08-2.43). Females were also more likely to report awareness of treatment options (OR = 1.48, 95% CI = 1.07-2.07) and to think that DMMs were helping their MS (OR = 1.32, 95% CI = 1.02-1.77). CONCLUSIONS: Female MS patients report better awareness of disease symptoms and have more positive perceptions of their ability to manage therapy with DMMs than male MS patients. These findings suggest that male MS patients may require additional education and support to manage their disease and therapy needs. Knowledge of these gender differences potentially could help managed care organizations to improve therapy adherence by guiding gender-specific patient support programs.

Effect of different exercise training intensities on musculoskeletal and neuropathic pain in inactive individuals with type 2 diabetes - Preliminary randomised controlled trial.

AIMS: People with type 2 diabetes (T2D) have a greater prevalence of musculoskeletal and neuropathic pain. This exploratory analysis investigated whether exercise of different intensities leads to changes in self-reported musculoskeletal pain or symptoms of diabetic neuropathy in inactive individuals with type 2 diabetes. METHODS: Thirty-two inactive adults with T2D (59% male, mean age 58.7 ± 9.1yrs, median HbA1c 7.8%) were randomised to usual care (CON), supervised combined aerobic and resistance moderate-intensity continuous training (C-MICT), or supervised combined high-intensity interval training (C-HIIT). At baseline and 8-weeks, musculoskeletal and neuropathic pain were evaluated using a modified Nordic Musculoskeletal Questionnaire and the Neuropathy Total Symptom Score-6 respectively. Quantitative sensory testing was used to determine thermal, mechanical and vibration detection thresholds, as well as pain pressure thresholds. Adverse events were recorded throughout the intervention. RESULTS: Compared to CON, reduction in musculoskeletal pain intensity was significantly greater for C-HIIT (MD -5.4, 95% CI [-10.6 to -0.2], p = 0.04) and non-significantly greater for C-MICT (MD -5.9 [-12.4 to 0.7], p = 0.08). Changes in neuropathy symptoms were not different between C-HIIT and CON (MD 1.0 [-0.9 to 2.8], p = 0.31), or C-MICT and CON (MD 0.2 [-3.1 to 3.6], p = 0.89). No differences in sensory function were observed between groups. Similar rates of adverse events were seen in both exercise interventions (19 C-HIIT; 17 C-MICT), all but one of which were mild. CONCLUSIONS: Preliminary data suggests 8-weeks of high-intensity combined aerobic and resistance exercise may be safely prescribed for inactive individuals with T2D and may reduce musculoskeletal pain but not neuropathic symptoms. TRIAL REGISTRATION: ACTRN12615000475549.

Not a Painless Condition: Rheumatological and Musculoskeletal Symptoms in Type 2 Diabetes, and the Implications for Exercise Participation.

OBJECTIVES: People with type 2 diabetes (T2D) are more likely to develop a range of rheumatological and musculoskeletal symptoms (RMS), and experience both chronic and widespread pain, compared with the general population. However, these symptoms are not commonly acknowledged by researchers, which hampers our understanding of the impact on this population. Since exercise is a key lifestyle management strategy for T2D and participation levels are typically low, understanding the potential impact of RMS on exercise participation is critical. The aim of this review is to summarise the literature regarding the prevalence and pathophysiology of RMS in T2D, the evidence for the benefits and risks associated with exercise on RMS, and the currently available tools for the reporting of RMS in both research studies and community settings. METHODS: A narrative review. RESULTS: There are numerous exercise trials in T2D, but few have sufficiently reported pain-related adverse events and even fewer have investigated the effects of exercise on RMS and chronic pain. DISCUSSION: Recommendations for future research are provided.

Potential Utility of Self-Report Measures of Affect to Optimise Exercise Adherence in People with Type 2 Diabetes.

Exercise is essential for managing type 2 diabetes, however approximately only 40% of people with the condition meet guidelines. The aim of this review is to examine the evidence regarding the use self-report measures of affect to understand and predict exercise adherence. Self-reported affect has been successfully used to regulate exercise intensity, monitor training load, prevent injury, and predict future physical activity participation in otherwise healthy and some clinical populations. Specific recommendations are provided for research to explore the utility of self-report measures of affect to promote exercise adherence in people with type 2 diabetes.

Impact of patient and plan design factors on switching to preferred statin therapy.

BACKGROUND: Changing formulary status is a common strategy to encourage greater use of lower-cost brand and generic drugs. OBJECTIVE: To examine the relationship between patient and plan design factors and formulary adherence after the formulary status change of atorvastatin. METHODS: We conducted a cross-sectional, cohort study of patients enrolled in one of 2139 commercial (no Medicare or Medicaid) plans that offer a 3-tier benefit design and changed atorvastatin from formulary to nonformulary status on January 1, 2006. Adults on atorvastatin therapy who were receiving targeted communications in the fourth quarter of 2005 were included for analysis. We used bivariate and multivariate logistic regression analyses to examine the relationship between covariates and formulary adherence for patients receiving atorvastatin through retail or home delivery (HD) pharmacies. RESULTS: A total of 211,083 patients met the study inclusion criteria, and more than 42% switched from atorvastatin to a formulary statin (33.1% retail, 51.8% HD). Patient-related factors that consistently and positively predicted switching across retail and HD channels included female sex, prior statin switching, and member outreach to the pharmacy benefit manager through telephone or Web use. Plan design factors that positively influenced switching to the preferred agent included step therapy, brand preferred/nonpreferred copayment differential, and among retail users, receipt of a rapid response education letter. Adoption of step therapy and the rapid-response program in retail settings increased the odds of switching by 1.3. Compared with patients who were paying a differential of $10 or less in retail channels, those who were paying $11-15, $16-20, and $21 and higher had increased odds of switching of 35% (95% CI 1.31 to 1.39), 41% (95% CI 1.37 to 1.46), and 80% (95% CI 1.74 to 1.86), respectively. In HD, compared with patients who were paying a differential of $15 or less, those who were paying $16-30, $31-40, and $41 and higher had increased odds of switching to a formulary preferred agent of 20% (95% CI 1.17 to 1.23), 23% (95% CI 1.19 to 1.26), and 59% (95% CI 1.55 to 1.64), respectively. CONCLUSIONS: Through appropriate program and plan design, plan sponsors' impact on formulary adoption is maximized.

Plan-sponsor savings and member experience with point-of-service prescription step therapy.

OBJECTIVE: To examine the effect of prescription step-therapy programs in terms of plan-sponsor savings and member experience at the point of service. STUDY DESIGN: Plan-sponsor savings were measured using a quasi-experimental, case-control design. Member experience with step therapy was measured using a self-administered mailed survey. METHODS: A 20,000-member plan implemented 3 step therapy programs in September 2002: proton pump inhibitors, selective serotonin reuptake inhibitors, and nonsteroidal anti-inflammatory drugs. Pharmacy claims from September 1, 2001, through June 30, 2003, were examined to compare changes in per-member-per-month (PMPM) net cost between the intervention group and a random sample of members from commercial plans without the step therapy programs. A mailed, self-administered survey was sent to members with a step edit from September 1, 2002 to December 31, 2002. RESULTS: The employer experienced a decrease of 0.83 dollars in net cost after implementing step therapy, while the comparison group had an upward trend of 0.10 dollars PMPM for these therapy classes. Member-reported outcomes indicated that approximately 30% of patients received a generic, 23% were granted a medical exception for the brand, 17% received no medication, and 16% paid the full retail price for the brand. If the pharmacist vs the patient contacted the physician, members were 8 times more likely to receive a medication covered by the health plan (OR, 8.10; 95% CI, 2.94-22.33 vs OR, 8.23; 95% CI, 3.11-21.93). Compared with those who received first-line therapy, those who paid out of pocket for the brand medication vs those who did not receive any medication were less likely to be satisfied with their pharmacy benefit (OR, 0.25; 95% CI, 0.08-0.80 vs OR, 0.12; 95% CI, 0.04-0.41). CONCLUSIONS: Step therapy produces significant drug savings. However, there appear to be opportunities to further members' and providers' understanding of these programs.

Verification of a decision analytic model assumption using real-world practice data: implications for the cost effectiveness of cyclo-oxygenase 2 inhibitors (COX-2s).

OBJECTIVE: To verify the gastroprotective agent (GPA) rate assumption used in cost-effectiveness models for cyclo-oxygenase 2 inhibitors (COX-2s) and to re-estimate model outcomes using GPA rates from actual practice. METHODS: Prescription and medical claims data obtained from January 1, 1999, through May 31, 2001, from a large preferred provider organization in the Midwest, were used to estimate GPA rates within 3 groups of patients aged at least 18 years who were new to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 therapy: all new NSAID users, new NSAID users with a diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), and a matched cohort of new NSAID users. RESULTS: Of the more than 319,000 members with at least 1 day of eligibility, 1900 met the study inclusion criteria for new NSAID users, 289 had a diagnosis of OA or RA, and 1232 were included in the matched cohort. Gastroprotective agent estimates for nonselective NSAID and COX-2 users were consistent across all 3 samples (all new NSAID users, new NSAID users with a diagnosis of OA or RA, and the matched cohort), with COX-2 GPA rates of 22%, 21%, and 20%, and nonselective NSAID GPA rates of 15%, 15%, and 18%, respectively. Re-estimation of the cost-effectiveness model increased the cost per year of life saved for COX-2s from $18,614 to more than $100,000. CONCLUSIONS: Contrary to COX-2 cost-effectiveness model assumptions, the rate of GPA use is positive and marginally higher among COX-2 users than among nonselective NSAID users. These findings call into question the use of expert opinion in estimating practice pattern model inputs prior to a product's use in clinical practice. A re-evaluation of COX-2 cost-effectiveness models is warranted.

Prescribing COX-2s for patients new to cyclo-oxygenase inhibition therapy.

OBJECTIVES: To profile the pattern of cyclo-oxygenase 2 inhibitor (COX-2) use, including length of therapy, medical conditions treated, and gastrointestinal (GI) risk profile of users. STUDY DESIGN: Descriptive retrospective analysis of medical and prescription claims data from a large preferred provider organization in the Midwest. METHODS: During an index period of January through May 31, 2000, patients new to COX-2 therapy were evaluated 365 days before and after their first prescription. Among the inclusion criteria, patients had to have no previous use of COX-2 therapy, be at least 18 years of age, and be continuously eligible during the entire study period. RESULTS: Of the more than 300 000 members with at least 1 day of coverage in the index window, 1312 members met the inclusion criteria. The average age of COX-2 users was 49.5 years (SD = 11.4) and 60% were female. The number of days' supply of COX-2 agent obtained by members was highly skewed, with a mean of 116 days (SD = 119.5) and a median of 60 days. The medical conditions associated with COX-2 use included a variety of musculoskeletal conditions, the most common being low back pain (22%) and osteoarthritis (18%). Approximately 19% of members did not have a diagnosis associated with COX-2 use. Sixty-five percent of those new to COX-2 therapy did not have an indication of being at risk for GI events, and 68% had no indication for trying a lower-cost nonselective nonsteroidal anti-inflammatory drug (NSAID) prescription prior to beginning COX-2 therapy. Taken together, 45% did not have a GI risk factor or prior use of nonselective NSAID prescription therapy. CONCLUSIONS: These findings suggest that opportunities exist to encourage the cost-effective prescribing of COX-2 therapy. Possible methods include implementation of step therapy, academic detailing, and physician education programs, among others.

Prescription use behavior among medicare beneficiaries with capped prescription benefits.

OBJECTIVE: To evaluate the strategies Medicare beneficiaries adopt to manage their out-of-pocket prescription costs in a prescription drug plan with maximum (.capped.) benefits and to evaluate differences in the likelihood of participating in any one strategy before and after exhaustion of capped prescription benefits. METHODS: Self-administered surveys were mailed to 786 Medicare+Choice members with capped annual prescription drug benefits of 500 dollars or 1,000 dollars. RESULTS: Two hundred twenty-one surveys were returned, for a 28% response rate. More than 70% of respondents participated in at least one strategy to manage prescription costs. The most frequently reported strategies included obtaining samples from their physician (45%), reducing spending on food and/or clothing (37%), shopping around at other pharmacies to obtain medications at a lower cost (29%), taking less than the prescribed amount (24%), receiving financial assistance from family or friends (17%), and stopping one or more regular-use medications (15%). More than two thirds of those who participated in at least one strategy participated in 2 or more strategies. While the combinations of strategies suggested prudence on the part of respondents (e.g., obtaining samples, shopping around), a subset of respondents participated in strategies that would be considered less desirable (e.g., stopping medications and taking less than prescribed). Finally, more than 35% indicated that they did not know their cap amount, and 24% did not know whether they had exhausted their benefit in 2000. CONCLUSION: These findings highlight the difficulties many Medicare beneficiaries face in managing prescription costs, even those with some coverage for prescription costs. In the design of prescription coverage for the elderly, policy makers should recognize the impact that capped benefits have on member behavior. The apparent high rate of reliance upon prescription drug samples to reduce prescription drug expenditures for many Medicare+Choice members raises the question of whether prescription drug samples may discourage the prescribing of lower-cost therapeutic alternatives.

Health plan member experience with point-of-service prescription step therapy.

OBJECTIVE: To better understand health plan member experience with point-of-service prescription step-therapy edits and outcomes in terms of drug received. METHODS: Self-administered mailed surveys were sent to 1,000 members who experienced a step-therapy edit from September 1, 2002, through January 31, 2003, for proton pump inhibitors or nonsteroidal anti-inflammatory drugs. Based upon these findings, a second survey was conducted by telephone among 617 members who experienced a step-therapy edit from January through April 25, 2003, and who had no subsequent prescription claim for the drug therapy class associated with the edit. RESULTS: The mailed survey generated a 23% response rate, and the telephone survey generated a 33% response rate. Just over 66% of the mail survey respondents indicated that they contacted their physician directly to try to remedy the situation, while 40% indicated that their pharmacist contacted their physician. Forty-four (44%) percent of members indicated that they received a different medication than was originally prescribed, 15% obtained prior authorization for the brand medication, 11% received no medication, 11% paid full price for the branded medication, 8% got an over-the-counter medication, and 4% received samples from their physician. Approximately 7% sought other means of obtaining coverage (i.e., they used spouse.s insurance) or did not remember the outcome. Member and pharmacy contact with the physician significantly influenced whether the member obtained a medication covered by their health plan (odds ratio [OR] = 6.5; 95% confidence interval [95% CI], 2.76-15.12 and OR = 4.6; 95% CI, 1.96-10.60, respectively). In a separate survey conducted by telephone among a different group of members, insight into reasons why members did not obtain any medication was obtained. Using a closed-ended question, 12% (n = 25) of members indicated receiving no medication. Upon further questioning, however, 32% of those who indicated that they had not received a medication said that they had in fact received a medication to treat their condition some time after the step edit. The second most common reason for not receiving a medication included issues related to cost (i.e., willingness to pay) or affordability (16% and 28%, respectively). CONCLUSIONS: The results of this study suggest that a majority of members receive a medication covered by their health plan subsequent to rejection of a claim for a prescribed drug that is the target of a step-therapy edit. However, there are opportunities for better member and provider communication designed to increase the use of first-line drugs and reduce the number of members paying out-of-pocket or receiving no medication.