Prevalence of Long COVID, and the Impact on Diabetes Management and Physical Activity Participation, in People with Type 2 Diabetes: An Australia-wide Cross-Sectional Online Survey.

BACKGROUND: The aim of this research was to understand the prevalence and impact of long COVID on people with type 2 diabetes (T2D). Specifically, to identify the proportion of people with T2D who have had COVID-19 and experience long COVID symptoms, and explore how these ongoing symptoms impact diabetes management and physical activity participation. METHODS: This study was an online survey of adults with T2D who had confirmed COVID-19 ≥12 weeks prior to participation, in Australia. Respondents were asked to report the presence (and severity) of long COVID symptoms, and for those with long COVID, the impact of their symptoms on diabetes management (blood glucose, body weight) and physical activity participation (activities of daily living, work/study, exercise). RESULTS: 1,046 people with T2D responded (median age 61.0[49.8-70.0]years; 56.0% male, 42.1% female, 1% non-binary/transgender; median T2D duration 10.0[5.0-18.0]years, median time since COVID-19 infection 33.0[20.3-36.1]weeks). Almost one third (30%) of respondents reported long COVID symptoms (present 12 weeks or more following most recent infection); 40% of respondents with long COVID symptoms reported a worsening of their diabetes management since their COVID-19 infection, with 29% reported trouble controlling their blood glucose and 43% reporting a higher body weight. Two thirds of respondents with ongoing symptoms reported that these symptoms moderately to severely impact their ability to perform activities of daily living, work, and/or exercise. The majority of those with long COVID reported reducing the frequency, duration, and/or intensity of exercise since their COVID-19 infection, with 36.1% not yet returning to their pre-infection exercise levels; 66% cite ongoing symptoms as the primary reason for this. CONCLUSIONS: Physical activity is a crucial component of diabetes management. However, the high prevalence of long COVID is hindering participation in this population, as well as deleteriously impacting diabetes management. Developing strategies to support people with T2D and long COVID to recommence safe levels of physical activity is of critical importance.

Outcomes of patients undergoing third hematopoietic cell transplantation for hematologic malignancies.

With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000-2020. Nine patients, with a median age of 18 (9-68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified. The median time between first HCT and HCT3 was 3.9 (0.7-13.6) years. Indication for HCT3 was relapse (n = 8) or graft failure (n = 1) after second HCT. At HCT3, seven of nine patients were in complete remission by flow cytometry. All experienced robust donor engraftment by one month after HCT3 (≥ 90% CD3) while one died at day + 24 of multi-organ failure and was not evaluable for chimerism. In total, eight patients died from relapse (n = 4), non-relapse, (n = 3) or unknown (n = 1) causes at a median of 0.6 (range, 0.1 - 9.9) years after HCT3. After HCT3, estimated overall survival at 6 months, 1 year, and 5 years was 88%, 63%, and 22%, respectively. In this highly selected group, HCT3 provided a treatment option although long-term survival was still dismal.

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 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.

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).

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.

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 .

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.

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.

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.

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.

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.

The influence of targeted education on medication persistence and generic substitution among consumer-directed health care enrollees.

OBJECTIVE: To evaluate an educational outreach among consumer-directed health plan (CDHP) enrollees on medication persistence and lower-cost generic substitution within four chronic medication therapies. STUDY SETTING: A cross-sectional analysis using pharmacy claims data from a national employer group that began offering a CDHP in 2006 and implemented an educational outreach to some CDHP enrollees in 2007 was used. METHODS: The intervention group was comprised of CDHP enrollees who received education outreach and was compared with CDHP enrollees without the educational outreach. Adjusted and unadjusted medication persistence and lower-cost generic substitutions were compared between groups. PRINCIPAL FINDINGS: There was no difference in medication persistence between groups. CDHP enrollees with the educational outreach were more likely to have converted to lower-cost generic alternative antihypertensive medication compared with CDHP enrollees without the educational outreach (OR(adj)=29.82, 95 percent CI=4.41-201.93). CONCLUSION: Educational outreach directed to CDHP enrollees was associated with increases in lower-cost generic alternatives with no change in patients' chronic medication use. However, considerable opportunity exists to assist CDHP enrollees in making sound health care decisions.

Patients' perceptions of generic medications.

Insurers and policymakers encourage the use of generic drugs to reduce costs, but generics remain underused. We conducted a national survey of commercially insured adults to evaluate their perceptions about generic drugs. Patients agreed that generics are less expensive and a better value than brand-name drugs, and are just as safe. However, although 56 percent reported that Americans should use more generics, only 37.6 percent prefer to take generics. We discuss perceptions about communicating with practitioners about generics, generic substitution, and policymakers' role in influencing generic use. These findings underscore the challenge that providers, insurers, and policymakers face in stimulating the cost-effective use of medications.

Lowering copayments: impact of simvastatin patent expiration on patient adherence.

OBJECTIVE: To assess the impact of a decrease in statin copayments on medication adherence and demand for statins. STUDY DESIGN: Quasi-experimental, pre/post design. METHODS: Patients in more than 700 health plans from June 2005 to May 2007 were evaluated. The intervention group (n = 13,319) and matched control group (n = 26,569) included patients who had at least 1 branded simvastatin or non-simvastatin statin purchase, respectively, before the simvastatin patent expired in June 2006. Intervention and control patients had to have purchased at least 1 generic simvastatin and non-simvastatin statin, respectively, after patent expiration. Intervention patients were matched to control patients up to 1:2 on incident statin use (yes/no) and pre-patent expiration copay (+/- $2). Adherence was calculated with the medication possession ratio (MPR). Adjusted and unadjusted changes in MPR were compared between groups. Elasticity of demand for statins was estimated. RESULTS: A small but statistically significant difference was observed between groups in the change in MPR (intervention = 0.52% adjusted mean increase, control = 2.02% adjusted mean decrease; adjusted P <.01). A marginally higher percentage of intervention patients (10.5%) compared with control patients (10.0%) increased their MPR from <80% in the preperiod to > or = 80% in the postperiod (adjusted P <.01). Elasticity of demand for statins was estimated at 0.02 and -0.02 for the copayment reduction categories of $0 to $5 and >$15, respectively. CONCLUSIONS: Decreasing statin copayments was associated with adherence increases. However, the overall increase in medication adherence was modest and its clinical significance uncertain.