Depression,Self-efficacy,and Adherence in Patients With Type 2 Diabetes

Depression and self-efficacy can be major factors in treatment adherence for patients with type 2 diabetes. Fifty-five adults with diabetes completed a depression inventory, a self-efficacy questionnaire, and a diabetes self-care inventory. As depressive symptoms increased, self-efficacy decreased (P = .000). As depressive symptoms increased, participants reported following the appropriate diet (P = .020) and exercise (P = .034) recommendations less often. Participants with higher self-efficacy were less likely to smoke (P = .031), and were more likely to adhere to diet (P = .000) and exercise (P = .000). Interventions should be multifaceted to address various factors that affect diabetes adherence.     

Randomized Controlled Trial of Insulin Supplementation for Correction of Bedtime Hyperglycemia in Hospitalized Patients With Type 2 Diabetes

OBJECTIVE

Clinical guidelines recommend point-of-care glucose testing and the use of supplemental doses of rapid-acting insulin before meals and at bedtime for correction of hyperglycemia. The efficacy and safety of this recommendation, however, have not been tested in the hospital setting.

RESEARCH DESIGN AND METHODS

In this open-label, randomized controlled trial, 206 general medicine and surgery patients with type 2 diabetes treated with a basal-bolus regimen were randomized to receive either supplemental insulin (n = 106) at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin (n = 100) except for BG >19.4 mmol/L. Point-of-care testing was performed before meals, at bedtime, and at 3:00 a.m. The primary outcome was the difference in fasting BG. In addition to the intention-to-treat analysis, an as-treated analysis was performed where the primary outcome was analyzed for only the bedtime BG levels between 7.8 and 19.4 mmol/L.

RESULTS

There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis.

CONCLUSIONS

The use of insulin supplements for correction of bedtime hyperglycemia was not associated with an improvement in glycemic control. We conclude that routine use of bedtime insulin supplementation is not indicated for management of inpatients with type 2 diabetes.     

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes.     

A Randomized Controlled Trial Comparing Motivational Interviewing in Education to Structured Diabetes Education in Teens With Type 1 Diabetes

OBJECTIVE

To compare motivational interviewing–based education (MI) and structured diabetes education (SDE) for improving A1C and psychosocial measures in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS

This study was a 9-month randomized controlled trial comparing MI (n = 21) to SDE (n = 23). Interventions were at baseline (T0) and 3 months (T1), with A1C and psychosocial measures obtained at 6 months (T2) and 9 months (T3).

RESULTS

Over the 6 months of follow-up, the SDE group had lower adjusted mean A1C value (least squares mean 10.31, SE 0.32) than the MI group (least squares mean 11.35, SE 0.34) (P = 0.03, d = −0.66). There were no differences on any of the psychosocial measures.

CONCLUSIONS

SDE is effective at improving metabolic control in adolescents with type 1 diabetes. Diabetes educators were proficient in learning MI.Adolescents with poorly controlled type 1 diabetes represent a challenge. They report adequate knowledge of diabetes, yet have poor compliance with self-care activities (1). They are difficult to engage and often demonstrate poor self-awareness regarding the need for change (2).     

Effects of Traditional Cupping Therapy in Patients With Carpal Tunnel Syndrome: A Randomized Controlled Trial

We investigated the effectiveness of cupping, a traditional method of treating musculoskeletal pain, in patients with carpal tunnel syndrome (CTS) in an open randomized trial. n = 52 outpatients (58.5 ± 8.0 years) with neurologically confirmed CTS were randomly assigned to either a verum (n = 26) or a control group (n = 26). Verum patients were treated with a single application of wet cupping, and control patients with a single local application of heat within the region overlying the trapezius muscle. Patients were followed up on day 7 after treatment. The primary outcome, severity of CTS symptoms (VAS), was reduced from 61.5 ± 20.5 to 24.6 ± 22.7mm at day 7 in the cupping group and from 67.1 ± 20.2 to 51.7 ± 23.9mm in the control group [group difference –24.5mm (95%CI –36.1; –2.9, P < .001)]. Significant treatment effects were also found for the Levine CTS-score (–.6 pts: 95%CI –.9; -.2, P = .002), neck pain (-12.6mm; 95%CI ?18.8; ?6.4, P < .001), functional disability (DASH-Score) (–11.1 pts; 95%CI –17.1; –5.1, P < .001), and physical quality of life (.3; 95%CI .0; .3, P = .048). The treatment was safe and well tolerated. We conclude that cupping therapy may be effective in relieving the pain and other symptoms related to CTS. The efficacy of cupping in the long-term management of CTS and related mechanisms remains to be clarified.PerspectiveThe results of a randomized trial on the clinical effects of traditional cupping therapy in patients with carpal tunnel syndrome are presented. Cupping of segmentally related shoulder zones appears to alleviate the symptoms of carpal tunnel syndrome.     

Cognitive Behavioral Therapy With Stabilization Exercises Affects Transverse Abdominis Muscle Thickness in Patients With Chronic Low Back Pain: A Double-Blinded Randomized Trial Study

ObjectiveNonspecific chronic low back pain (NCLBP) is a major public health and global socioeconomic burden with a variety of symptoms, such as fear-avoidance behaviors. This study aimed to evaluate the effect of cognitive behavioral therapy (CBT) associated with stabilization exercise (SE) on thickness of transverse abdominis (TrA) muscle in patients with NCLBP.MethodsForty patients with NCLBP were randomly assigned into experimental CBT associated with SE (n = 20) and control groups without SE (n = 20). Transverse abdominis muscle thickness was assessed during abdominal drawing in maneuver (ADIM) and active straight leg raise (ASLR) of the right lower limb using ultrasound imaging. Fear-avoidance belief and disability were evaluated using a fear-avoidance belief questionnaire (FABQ) and a Roland-Morris disability questionnaire (RMDQ) before and after intervention.ResultsMixed-model analysis of variance indicated that the effect of time was significant for the right and left TrA contraction thickness during ADIM and left TrA contraction thickness during ASLR (P < .05). However, the experimental group exhibited higher right and left TrA muscle thickness compared with the control group during ADIM (P = .001). Moreover, there were no significant differences between groups in the thickness of TrA muscle during ASLR (P > .05). The effect of time was significant for FABQ (P = .02) and RMDQ (P = .01); however, the effect of group was significant for the FABQ after intervention (P = .04).ConclusionsStabilization exercise associated with CBT is more effective than SE alone in improving fear avoidance belief and in increasing the thickness of the TrA muscle during ADIM task.     

Lixisenatide Treatment for Older Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetics: Meta-Analysis of Five Randomized Controlled Trials

Aim

Evaluate the efficacy and safety of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in older patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on oral antidiabetics (OADs).

Methods

A meta-analysis was conducted on data from older patients (≥65 years) from five of the GetGoal trials, in which patients with T2DM were treated with lixisenatide 20 µg once daily or placebo, as an add-on to OADs. The primary endpoint in all trials was change from baseline at week 24 in glycated hemoglobin (HbA_1c). Other endpoints included changes in post-prandial plasma glucose (PPG), fasting plasma glucose (FPG) and weight. Composite and safety endpoints were also analyzed.

Results

A total of 501 patients aged ≥65 years were included in this meta-analysis: 304 received lixisenatide plus OADs and 197 received placebo as add-on to OADs. Lixisenatide as an add-on to OADs significantly reduced HbA_1c, PPG, FPG and weight, with placebo-corrected treatment effects at week 24 of ?0.54% (p < 0.0001), ?126 mg/dL (p < 0.0001), ?13 mg/dL (p = 0.0005) and ?0.90 kg (p = 0.0021), respectively. Patients receiving lixisenatide plus OADs were significantly more likely to achieve composite (HbA_1c levels <7%, HbA_1c levels <7% and no symptomatic hypoglycemia, and HbA_1c levels <7%, no weight gain and no symptomatic hypoglycemia) and safety endpoints than those receiving placebo plus OADs. Symptomatic hypoglycemia was experienced by 8.55% and 3.55% of patients in the lixisenatide plus OADs and placebo plus OADs groups, respectively (p = 0.0276), although no serious hypoglycemic episodes were reported.

Conclusions

Lixisenatide plus OADs improved glycemic control in older patients inadequately controlled on OADs compared with placebo plus OADs. Lixisenatide is well tailored to the pathophysiology of T2DM in older patients.     

Effects of Cardiovascular Disease Risk Communication for Patients With Type 2 Diabetes on Risk Perception in a Randomized Controlled Trial: The @RISK Study

OBJECTIVE

Patients with type 2 diabetes mellitus (T2DM) underestimate their risk of developing severe complications, and they do not always understand the risk communication by their caregivers. The aim of this study was to investigate the effects of an intervention focused on the communication of the absolute 10-year risk of developing cardiovascular disease (CVD) in patients with T2DM.

RESEARCH DESIGN AND METHODS

A randomized controlled trial was performed in T2DM patients newly referred to the Diabetes Care System (DCS) West-Friesland, a managed-care system in the Netherlands. The intervention group (n = 131) received a six-step CVD risk communication. Control subjects (n = 130) received standard managed care. The primary outcome measure was appropriateness of risk perception (difference between actual CVD risk calculated by the UK Prospective Diabetes Study risk engine and risk perception). Secondary outcome measures were illness perceptions, attitude and intention to change behavior, satisfaction with the communication, and anxiety and worry about CVD risk. Patients completed questionnaires at baseline, at 2 weeks (immediately after the intervention), and at 12 weeks.

RESULTS

Appropriateness of risk perception improved between the intervention and control groups at 2 weeks. This effect disappeared at 12 weeks. No effects were found on illness perceptions, attitude and intention to change behavior, or anxiety and worry about CVD risk. Patients in the intervention group were significantly more satisfied with the communication.

CONCLUSIONS

This risk communication method improved patients’ risk perception at 2 weeks but not at 12 weeks. Negative effects were not found, as patients did not become anxious or worried after the CVD risk communication.Care for patients with type 2 diabetes mellitus (T2DM) is focused on optimal control of the disease and the prevention of the development of severe complications, in particular cardiovascular disease (CVD) (1). Increasing evidence suggests that patients who take a more active role in their care achieve better health outcomes (2), and appropriate risk communication may facilitate this process (3). Although studies have shown that general risk communication is helpful for patients with T2DM, studies incorporating patients’ individual risk are scarce, and, in particular, the effects on the intention to perform self-management activities are unclear (4–7).In the current study, a cardiovascular risk communication intervention was developed for T2DM patients incorporating the individual risk for CVD. Three principles that have been shown to be important in risk communication were used in the development of this intervention. The first principle was to provide a simple and clear message on the causes and consequences of the risk of developing CVD and on what actions can possibly prevent CVD (3,8). The second was to use a simple format, such as visual presentations of the risk rather than percentages, which patients might be able to better understand, although evidence is mixed (5,9–14). Third, communication of the benefits of change in a so-called positive frame, rather than a negative presentation—for example, in terms of loss of healthy years—has been shown to increase patients’ motivation (4,13,15). The rationale for this study was based on Leventhal’s self-regulation theory and the Theory of Planned Behavior (TPB). According to the self-regulation theory, patients have perceptions concerning their disease that are either correct or incorrect (16,17). These perceptions determine how patients cope with their disease and manage their risks of developing complications (18). It is hypothesized that providing understandable risk information may change the illness perceptions, which in turn may change the attitude concerning importance of behavior change and intention to change—as laid down in the TPB (19).The aim of the current study was to investigate the effects of a CVD risk communication intervention on appropriateness of risk perception in patients with T2DM. Secondary objectives were to investigate the effects on illness perceptions, attitude, and intention to change behavior. In addition, patients’ general satisfaction with the communication and anxiety and worry about CVD risk were assessed to check for adverse effects of risk communication.     

A Randomized Controlled Trial on the Effects of Low-Dose Extracorporeal Shockwave Therapy in Patients With Knee Osteoarthritis

ObjectiveTo test the efficacy of low-dose extracorporeal shockwave therapy (ESWT) on osteoarthritis knee pain, lower limb function, and cartilage alteration for patients with knee osteoarthritis.DesignRandomized controlled trial with placebo control.SettingOutpatient physical therapy clinics within a hospital network.ParticipantsEligible volunteers (N=63) with knee osteoarthritis (Kellgren-Lawrence grade II or III) were randomly assigned to 2 groups.InterventionsPatients in the experimental group received low-dose ESWT for 4 weeks while those in the placebo group got sham shockwave therapy. Both groups maintained a usual level of home exercise.Main Outcome MeasuresKnee pain and physical function were measured using a visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index at baseline, 5 weeks, and 12 weeks. Cartilage alteration was measured analyzing the transverse relaxation time (T2) mapping.ResultsThe VAS score, WOMAC, and Lequesne index of the ESWT group were significantly better than those of the placebo group at 5 and 12 weeks (P<.05). Both groups showed improvement in pain and disability scores over the 12-week follow-up period (P<.05). In terms of imaging results, there was no significant difference in T2 values between groups during the trial, although T2 values of the ESWT group at 12 weeks significantly increased compared to those at baseline (P=.004). The number and prevalence of adverse effects were similar between the 2 groups, and no serious side effects were found.ConclusionsA 4-week treatment of low-dose ESWT was superior to placebo for pain easement and functional improvement in patients with mild to moderate knee osteoarthritis but had some negative effects on articular cartilage.     

Cognitive Behavioral Therapy Versus Progressive Muscle Relaxation Training for Multiple Somatoform Symptoms: Results of a Randomized Controlled Trial

Although unexplained multiple symptoms and somatoform disorders are a highly prevalent condition in primary practice, few randomized controlled trials of cognitive behavioral therapy (CBT) have been conducted. Moreover, most of these trials have used only the usual medical treatment or wait list control groups. The present study included 134 outpatients showing at least two medically unexplained symptoms. They were randomly assigned to eight weekly group sessions of either CBT or progressive muscle relaxation (PMR) or wait list control and were assessed before and after treatment as well as 6 months after the end of treatment. The number and intensity of somatoform symptoms were the primary outcome measures; depression, anxiety and physical and mental health constituted the secondary outcome measures. CBT showed small effects (Cohen’s d = 0.44) for the treatment of somatoform disorders. Benefits of the treatment were sustained over 6 months of follow-up. However, no differential effects of CBT and PMR were found. In conclusion, both CBT and PMR appear to be effective treatments for multiple somatoform symptoms.     

Yoga,Eurythmy Therapy and Standard Physiotherapy (YES-Trial) for Patients With Chronic Non-specific Low Back Pain: A Three-Armed Randomized Controlled Trial

We aimed to evaluate the effects of yoga and eurythmy therapy compared to conventional physiotherapy exercises in patients with chronic low back pain. In a three-armed, multicentre, randomized controlled trial, patients with chronic low back pain were treated for 8 weeks in group sessions (75 minutes once per week). Primary outcome was patients’ physical disability (measured by RMDQ) from baseline to week 8. Secondary outcome variables were pain intensity and pain-related bothersomeness (VAS), health-related quality of life (SF-12) and life satisfaction (BMLSS). Outcomes were assessed at baseline, after the intervention at 8 weeks and at a 16-week follow up. Data of 274 participants were used for statistical analyses. There were no significant differences between the three groups for the primary and all secondary outcomes. In all groups, RMDQ decreased comparably at 8 weeks, but did not reach clinical meaningfulness. Pain intensity and pain-related bothersomeness decreased, while quality of life increased in all 3 groups. In explorative general linear models for the SF-12’s mental health component participants in the eurythmy arm benefitted significantly more compared to physiotherapy and yoga. Furthermore, within-group analyses showed improvements of SF-12 mental score for yoga and eurythmy therapy only. All interventions were safe.Clinical Trials Register: DRKS-ID: DRKS00004651Perspective: This article presents the results of a multicentre three-armed randomized controlled trial on the clinical effects of three 8-week programs in patients with chronic low back pain. Compared to the ‘gold standard’ of conventional physiotherapeutic exercises, eurythmy therapy and yoga therapy lead to comparable symptomatic improvements in patients with chronic low back pain. However, the within-group effect sizes were small to moderate and did not reach clinical meaningfulness on patients’ physical disability (RMDQ).     

Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11)

OBJECTIVETo compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.RESEARCH DESIGN AND METHODSPatients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA_1c reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients.RESULTSMean baseline HbA_1c and BMI in randomly assigned patients (N = 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m², respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA_1c reductions compared with 1.5 mg (treatment-regimen estimand: −1.77 vs. −1.54% [−19.4 vs. −16.8 mmol/mol], estimated treatment difference [ETD] −0.24% (−2.6 mmol/mol), P < 0.001; efficacy estimand: −1.87 vs. −1.53% [−20.4 vs. −16.7 mmol/mol], ETD −0.34% (−3.7 mmol/mol), P < 0.001). Dulaglutide 3.0 mg was superior to 1.5 mg for reducing HbA_1c, using the efficacy estimand (ETD −0.17% [−1.9 mmol/mol]; P = 0.003) but not the treatment-regimen estimand (ETD −0.10% [−1.1 mmol/mol]; P = 0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment regimen: −4.6 vs. −3.0 kg, ETD −1.6 kg, P < 0.001; efficacy: −4.7 vs. −3.1 kg, ETD −1.6 kg, P < 0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%).CONCLUSIONSIn patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA_1c and body weight with a similar safety profile.     

The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy

OBJECTIVE

A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone.

RESEARCH DESIGN AND METHODS

A total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a day) or placebo added to a stable dose of metformin (1,500–2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio.

RESULTS

After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was −0.44% (P < 0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (−0.91 mg/dL and −7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally well-tolerated with a comparable safety profile to metformin-placebo.

CONCLUSIONS

Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes.Imeglimin is the first in a new tetrahydrotriazine-containing class of oral antidiabetic agents, the glimins. Imeglimin decreases hepatic glucose production, increases muscle glucose uptake, and improves pancreatic glucose-dependent insulin secretion (1).Previous studies have demonstrated imeglimin to be as effective as metformin in improving glycemia (2). Since metformin is the preferred first-line therapy for type 2 diabetes, the current study examined the efficacy, safety, and tolerability of imeglimin in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone.     

Music Therapy Reduces Pain in Palliative Care Patients: A Randomized Controlled Trial

ContextTreatment of pain in palliative care patients is challenging. Adjunctive methods of pain management are desirable. Music therapy offers a nonpharmacologic and safe alternative.ObjectivesTo determine the efficacy of a single music therapy session to reduce pain in palliative care patients.MethodsTwo hundred inpatients at University Hospitals Case Medical Center were enrolled in the study from 2009 to 2011. Patients were randomly assigned to one of two groups: standard care alone (medical and nursing care that included scheduled analgesics) or standard care with music therapy. A clinical nurse specialist administered pre- and post-tests to assess the level of pain using a numeric rating scale as the primary outcome, and the Face, Legs, Activity, Cry, Consolability Scale and the Functional Pain Scale as secondary outcomes. The intervention incorporated music therapist-guided autogenic relaxation and live music.ResultsA significantly greater decrease in numeric rating scale pain scores was seen in the music therapy group (difference in means [95% CI] ?1.4 [?2.0, ?0.8]; P < 0.0001). Mean changes in Face, Legs, Activity, Cry, Consolability scores did not differ between study groups (mean difference ?0.3, [95% CI] ?0.8, 0.1; P > 0.05). Mean change in Functional Pain Scale scores was significantly greater in the music therapy group (difference in means ?0.5 ([95% CI] ?0.8, 0.3; P < 0.0001).ConclusionA single music therapy intervention incorporating therapist-guided autogenic relaxation and live music was effective in lowering pain in palliative care patients.     

Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes

OBJECTIVE

Quick-release bromocriptine (bromocriptine-QR), a D2 dopamine receptor agonist, is indicated as a treatment for type 2 diabetes. The Cycloset Safety Trial, a 52-week, randomized, double-blind, multicenter trial, evaluated the overall safety and cardiovascular safety of this novel therapy for type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 3,095 patients with type 2 diabetes were randomized 2:1 to bromocriptine-QR or placebo in conjunction with the patient''s usual diabetes therapy (diet controlled only or up to two antidiabetes medications, including insulin). The all-cause–safety end point was the occurrence of any serious adverse event (SAE), with a hazard ratio (HR) noninferiority margin of 1.5. In a prespecified analysis, the frequency of cardiovascular disease (CVD) events defined as a composite of myocardial infarction, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure was evaluated using modified intent-to-treat analysis (clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00377676","term_id":"NCT00377676"}}NCT00377676).

RESULTS

In the bromocriptine-QR group, 176 (8.6%) people reported SAEs compared with 98 (9.6%) in the placebo group (HR 1.02 [96% one-sided CI 1.27]). Fewer people reported a CVD end point in the bromocriptine-QR group versus the placebo group (37 [1.8%] vs. 32 [3.2%], respecively) (HR 0.60 [95% two-sided CI 0.35–0.96]). Nausea was the most commonly reported adverse event in the bromocriptine-QR group.

CONCLUSIONS

The frequency of SAEs was comparable between the treatment arms. Compared with patients in the placebo arm, fewer patients taking bromocriptine-QR experienced a cardiovascular end point.Type 2 diabetes is a growing global pandemic that is estimated to afflict approximately 350 million people by the year 2030 (1,2). This growing threat to human health requires medical interventions to lessen the morbidity associated with type 2 diabetes. Results from several recent clinical trials have raised concerns about the cardiovascular safety of current therapies and therapeutic strategies (3–10). Therefore, the U.S. Food and Drug Administration has established cardiovascular safety standards that must be met for type 2 diabetes therapies prior to their marketing approval. The Cycloset Safety Trial was designed to assess the overall safety and specifically address cardiovascular safety for a novel treatment for type 2 diabetes, quick-release bromocriptine (bromocriptine-QR) (11).Bromocriptine is a dopamine D2 receptor agonist, and bromocriptine-QR was designed to provide a short duration pulse of this dopamine agonist to centers in the brain (12,13) that regulate peripheral fuel metabolism (14). Bromocriptine-QR is administered in the morning, within 2 h of waking, to effectuate an increase in central dopaminergic tone at the time of day it normally peaks in healthy individuals (15). This circadian peak in central dopaminergic tone has been linked to preservation and/or induction of normal insulin sensitivity and glucose metabolism in several preclinical studies (14). Although bromocriptine-QR had demonstrated improvements in various metabolic parameters in patients with type 2 diabetes as well as improvements in many surrogate markers of cardiovascular disease, (16,17) data from these previous clinical studies were insufficiently powered to adequately assess cardiovascular safety. This article reports the results of a 1-year, double-blind, placebo-controlled, randomized clinical trial where the overall safety and specifically cardiovascular safety of bromocriptine-QR was the primary outcome.     

Efficacy of Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A Randomized Controlled Trial (IMPACT Study)

This study examined the efficacy of adding a remote, synchronous, group, videoconference-based form of acceptance and commitment therapy (ACT) or behavioral activation therapy for depression (BATD) to treatment-as-usual (TAU) in 234 patients with chronic low back pain (CLBP) plus comorbid depressive symptoms. Participants were randomly assigned to ACT, BATD, or TAU. Compared to TAU, ACT produced a significant reduction in pain interference at posttreatment (d = .64) and at follow-up (d = .73). BATD was only superior to TAU at follow-up (d = .66). A significant reduction in pain catastrophizing was reported by patients assigned to ACT and BATD at posttreatment (d = .45 and d = .59, respectively) and at follow-up (d = .59, in both) compared to TAU. Stress was significantly reduced at posttreatment by ACT in comparison to TAU (d = .69). No significant between-group differences were found in depressive or anxiety symptoms. Clinically relevant number needed to treat (NNT) values for reduction in pain interference were obtained at posttreatment (ACT vs TAU = 4) and at follow-up (ACT vs TAU = 3; BATD vs TAU = 5). In both active therapies, improvements in pain interference at follow-up were significantly related to improvements at posttreatment in psychological flexibility. These findings suggest that new forms of cognitive-behavioral therapy are clinically useful in improving pain interference and pain catastrophizing. Further research on evidence-based change processes is required to understand the therapeutic needs of patients with chronic pain and comorbid conditions.Trial numberNCT04140838.PerspectiveGroup videoconference-based ACT and BATD showed greater efficacy than TAU for reducing pain interference and pain catastrophizing in patients with CLBP plus clinically relevant depression. Psychological flexibility appeared to be the main contributor to treatment effects for both ACT and BATD.