Health-Related Quality of Life in Low-Income Older African Americans

This study examined the relationships among comorbid conditions, symptom stress, depression, functional status and health-related quality of life (HRQOL) in low-income older African Americans with chronic diseases. A convenience sample of 83 older African American adults living in subsidized housing for elders participated in the study. Data were collected in face-to-face interviews. Participants reported lower scores on HRQOL than the SF-36 norms for age 60 or older in the general U.S. population. Comorbid conditions, symptom distress, depression, and functional status significantly predicted both the physical (F = 38.92, p < .001) and mental (F = 23.21, p < .001) health components of HRQOL, accounting for 63% of variance in the SF-36 physical health score and 55% of the variance in the SF-36 mental health score. The findings suggested that developing interventions to assist older African Americans to better manage their symptoms and depression are of prime importance for improving HRQOL.     

Etanercept Treatment in Children With New-Onset Type 1 Diabetes: Pilot randomized, placebo-controlled, double-blind study

OBJECTIVE

To gather preliminary data on the feasibility and efficacy of etanercept therapy to prolong endogenous insulin production in pediatric patients with newly diagnosed type 1 diabetes.

RESEARCH DESIGN AND METHODS

This was a 24-week double-blind, randomized, placebo-controlled study conducted at the Diabetes Center, Women and Children''s Hospital of Buffalo. Eighteen subjects (11 male and 7 female, aged 7.8–18.2 years) were randomly assigned to receive either placebo or etanercept. Inclusion criteria included age 3–18 years, GAD-65 and/or islet cell antibody positivity, A1C >6%, three insulin injections per day, white blood cell count 3,000–10,000, platelets >100,000, and normal liver and renal function. Intention-to-treat analysis was used.

RESULTS

A1C at week 24 was lower in the etanercept group (5.91 ± 0.5%) compared with that in the placebo group (6.98 ± 1.2%; P < 0.05) with a higher percent decrease from baseline than in the placebo group (etanercept 0.41 ± 0.1 vs. placebo 0.18 ± 0.21; P < 0.01). The percent change in C-peptide area under the curve from baseline to week 24 showed a 39% increase in the etanercept group and a 20% decrease in the placebo group (P < 0.05). From baseline to week 24 insulin dose decreased 18% in the etanercept group compared with a 23% increase in the placebo group (P < 0.05). Seventeen patients completed the study, and none withdrew because of adverse events.

CONCLUSIONS

In this small pilot study, treatment of pediatric patients newly diagnosed with type 1 diabetes with etanercept resulted in lower A1C and increased endogenous insulin production, suggesting preservation of β-cell function. A larger study is needed to further explore safety and efficacy.Type 1 diabetes is a T-cell–mediated autoimmune disease characterized by selective destruction of insulin-producing β-cells within the pancreatic islet. This chronic disease affects 1 in 400–600 youth and poses a significant medical and psychological burden on patients and their families (1–3). In most patients, diagnosis and treatment are followed by a “partial remission period” (honeymoon period) during which transient partial recovery of endogenous insulin production occurs. Eventually, there is progressive, irreversible β-cell demise, leaving the patient totally dependent on exogenous insulin administered via multiple daily injections or continuous subcutaneous insulin infusion. Thus, the partial remission period represents a window of opportunity to halt the progression of the disease. Several clinical studies are currently conducted to test agents that may alter the natural history of type 1 diabetes.Tumor necrosis factor-α (TNF-α) and other cytokines play a role in the autoimmune process leading to pancreatic destruction (4,5). Evidence suggesting that TNF-α plays an active role in the pathogenesis of type 1 diabetes is derived from in vitro studies and animal models. In the nonobese diabetic mouse, TNF-α mRNA is produced by CD4⁺ T-cells within inflamed islets during the development of diabetes (6). In vitro models show that TNF-α potentiates the direct functional inactivation and destruction of β-cells by other cytokines such as interleukin-1β and interferon-γ (7–11). Transgenic mice with increased β-cell expression of TNF-α have significant lymphocytic insulinitis, which is abrogated in TNF receptor–null mice (12). These findings support the role of TNF-α in signaling lymphocytic invasion, promoting local inflammation within pancreatic islets and contributing to cytokine-induced β-cell destruction.Etanercept is a recombinant soluble TNF-α receptor fusion protein that binds to TNF-α. It acts by clearing TNF-α from the circulation, thereby blocking the biological activity of this inflammatory cytokine. Although etanercept is used in the treatment of many autoimmune diseases including ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, and rheumatoid arthritis, it has never been tested in youth with type 1 diabetes (13,14).We hypothesized that the administration of etanercept to children newly diagnosed with type 1 diabetes may prolong the partial remission period. The aim of this pilot study was to gather preliminary data on the feasibility and efficacy of etanercept administration to pediatric patients with recently diagnosed type 1 diabetes. The primary end points of this study were percent change from baseline for A1C and for C-peptide area under the curve (AUC). Secondary end points were insulin dose change from baseline and number of insulin injections discontinued, if any.     

Collaborative Care Management of Major Depression Among Low-Income, Predominantly Hispanic Subjects With Diabetes: A randomized controlled trial

OBJECTIVE

To determine whether evidence-based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects.

RESEARCH DESIGN AND METHODS

This was a randomized controlled trial of 387 diabetic patients (96.5% Hispanic) with clinically significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months. Intervention (INT group) included problem-solving therapy and/or antidepressant medication based on a stepped-care algorithm; first-line treatment choice; telephone treatment response, adherence, and relapse prevention follow-up over 12 months; plus systems navigation assistance. Enhanced usual care (EUC group) included standard clinic care plus patient receipt of depression educational pamphlets and a community resource list.

RESULTS

INT patients had significantly greater depression improvement (≥50% reduction in Symptom Checklist-20 depression score from baseline; 57, 62, and 62% vs. the EUC group''s 36, 42, and 44% at 6, 12, and 18 months, respectively; odds ratio 2.46–2.57; P < 0.001). Mixed-effects linear regression models showed a significant study group–by–time interaction over 18 months in diabetes symptoms; anxiety; Medical Outcomes Study Short-Form Health Survey (SF-12) emotional, physical, and pain-related functioning; Sheehan disability; financial situation; and number of social stressors (P = 0.04 for disability and SF-12 physical functioning, P < 0.001 for all others) but no study group–by–time interaction in A1C, diabetes complications, self-care management, or BMI.

CONCLUSIONS

Socioculturally adapted collaborative depression care improved depression, functional outcomes, and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics.Diabetes is associated with a twofold higher risk of comorbid depression compared with the general population, with rates among Hispanics as high as 33% (1). Greater risk of cardiovascular illness, functional disability, mortality, and health service use is found among Hispanics with comorbid depression and diabetes, which is particularly important because Hispanics have a higher prevalence of diabetes compared with non-Hispanic whites (2). Moreover, among diabetic patients, depression is often persistent and severe (2), and among Hispanics, difficulty with diabetes management can contribute to depression (3). However, Hispanics are less likely to be diagnosed or to receive depression care and have lower utilization rates and greater risk of discontinuing antidepressants during the first 30 days of treatment because of side effects, socioeconomic barriers, and cultural preferences for psychotherapy (4).Glycemic control is worse and complications are high among Hispanics with diabetes (5), in part, explained by inadequate medical and self-care and cultural and economic factors (6). Comorbid depression and diabetes may significantly worsen the course of both disorders, leading to higher complication and mortality rates (7) and total health care expenditures (8). Depression may worsen diabetes outcomes via neurobiological mechanisms (9) and poor adherence to self-care regimens (10). In some, but not all, trials, glucose control has been shown to improve with depression treatment; however, the prevalence of undiagnosed or untreated depression among all diabetic subjects is high (11).This randomized clinical trial implemented a health services effectiveness trial design to test a collaborative care model aimed at increasing exposure of low-income, predominantly Hispanic diabetic patients (15 non-Hispanics) with comorbid depression to evidenced-based depression psychotherapy and/or pharmacotherapy to examine both depression care receipt and outcomes compared with usual care. We hypothesized that the intervention (INT group) versus enhanced usual care (EUC group) would be associated with improved depressive symptom outcomes, functioning, quality of life, and A1C levels at 6, 12, and 18 months. Sociocultural adaptations (12,13) were aimed at enhancing patient depression treatment engagement and adherence; reducing individual, provider, and system barriers to care; integrating depression and diabetes care; and providing culturally and linguistically competent care.     

Health-Related Quality of Life, Treatment Satisfaction, and Costs Associated With Intraperitoneal Versus Subcutaneous Insulin Administration in Type 1 Diabetes: A randomized controlled trial

OBJECTIVE

To investigate the effects of continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin on health-related quality of life (HRQOL) and treatment satisfaction, and to perform a cost analysis in type 1 diabetes.

RESEARCH DESIGN AND METHODS

We used an open-label, prospective, crossover, randomized, 16-month study (N = 24). HRQOL and patient satisfaction were assessed with questionnaires (the 36-item short-form health survey [SF-36], the World Health Organization-Five Well-Being Index [WHO-5], and the Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Direct costs of CIPII and continuous subcutaneous insulin infusion (CSII) were compared.

RESULTS

Questionnaire scores were higher with CIPII than with subcutaneous therapy. Yearly direct pump- and procedure-associated costs for CIPII were estimated at €10,910 compared with €4,810 for CSII.

CONCLUSIONS

Apart from improving glycemic control, CIPII improved HRQOL and treatment satisfaction compared with subcutaneous insulin. Direct pump- and procedure-associated costs are considerably higher for CIPII, however.We recently showed that treatment with continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin results in better glycemic control, expressed as a 0.8%-point decrease in A1C (1). The aim of the current analysis was to assess the effects of CIPII on health-related quality of life (HRQOL) and treatment satisfaction compared with intensified subcutaneous insulin therapy, and to provide up-to-date cost calculations of direct pump- and procedure-associated costs.     

Exercise Training and Quality of Life in Individuals With Type 2 Diabetes: A randomized controlled trial

OBJECTIVE

To establish whether exercise improves quality of life (QOL) in individuals with type 2 diabetes and which exercise modalities are involved.

RESEARCH DESIGN AND METHODS

Health Benefits of Aerobic and Resistance Training in individuals with type 2 Diabetes (HART-D; n = 262) was a 9-month exercise study comparing the effects of aerobic training, resistance training, or a combination of resistance and aerobic training versus a nonexercise control group on hemoglobin A_1c (HbA_1c) in sedentary individuals with type 2 diabetes. This study is an ancillary analysis that examined changes in QOL after exercise training using the Short Form-36 Health Survey questionnaire compared across treatment groups and with U.S. national norms.

RESULTS

The ancillary sample (n = 173) had high baseline QOL compared with U.S. national norms. The QOL physical component subscale (PCS) and the general health (GH) subscale were improved by all three exercise training conditions compared with the control group condition (resistance: PCS, P = 0.005; GH, P = 0.003; aerobic: PCS, P = 0.001; GH, P = 0.024; combined: PCS, P = 0.015; GH, P = 0.024). The resistance training group had the most beneficial changes in bodily pain (P = 0.026), whereas physical functioning was most improved in the aerobic and combined condition groups (P = 0.025 and P = 0.03, respectively). The changes in the mental component score did not differ between the control group and any of the exercise groups (all P > 0.05). The combined training condition group had greater gains than the aerobic training condition group in the mental component score (P = 0.004), vitality (P = 0.031), and mental health (P = 0.008) and greater gains in vitality compared with the control group (P = 0.021).

CONCLUSIONS

Exercise improves QOL in individuals with type 2 diabetes. Combined aerobic/resistance exercise produces greater benefit in some QOL domains.Quality of life (QOL) is a comprehensive construct that typically includes physical, emotional, and social aspects of well-being, such as physical functioning, role limitations attributable to physical or emotional problems, bodily pain, and energy level (1). Previous exercise studies in healthy subjects and individuals with cardiovascular disease risk or other medical conditions (i.e., hypertension, chronic obstructive pulmonary disease [COPD], cancer) have found significant improvements in QOL after exercise training (2–6). Although most of these previous studies were small and not randomized controlled trials, recent data have provided more convincing evidence of the beneficial effects of exercise on QOL. Specifically, Martin et al. (4) in a large randomized controlled trial (N = 430) found a significant increase in most QOL domains in response to three different amounts of aerobic exercise training in overweight and obese postmenopausal women with high blood pressure. In addition, QOL improved with greater amounts of exercise training in a dose-dependent manner (4).Adults with diabetes report a lower QOL than nondiabetic individuals (1,6), and exercise training may have promise for improving QOL in individuals with type 2 diabetes (4). Physical activity interventions have been shown to improve glycemic control (7,8). Given that poor glycemic control is a potential mediator between diabetes and QOL (9) changes in hemoglobin A_1c (HbA_1c) occurring as a result of an exercise intervention may lead to improvements in QOL. To date, limited data exist regarding the effects of exercise training on QOL in sedentary adults with type 2 diabetes. Although exercise training interventions generally have shown beneficial effects on QOL in diabetic populations, many of these studies used small sample sizes, short follow-up periods, and self-directed exercise interventions rather than well-verified, supervised exercise interventions (10–13). However, two recently published trials overcame many of these limitations (14,15). Reid et al. (14) performed an analysis of QOL data from the Diabetes Aerobic and Resistance Exercise (DARE) trial, in which 218 individuals were randomized to a 22-week intervention comprising aerobic exercise only, resistance training only, combined training (aerobic and resistance), or no-exercise control condition. The authors found that mental health QOL improvements were greater in the control group compared with the resistance and the combined training groups. In addition, physical QOL improved in the resistance training group compared with the control group. Nicolucci et al. (15) examined QOL from the Italian Diabetes and Exercise Study (IDES) in which 606 individuals received either 150 min/week of supervised, progressive, mixed (aerobic and resistance) training plus exercise counseling versus counseling alone. Their results demonstrated improved QOL with increasing exercise volume.Thus, past studies have provided evidence for a beneficial effect of exercise training interventions on QOL in nonmedically ill and in chronically ill populations; however, the largest trials to date conflict on whether exercise benefits mental health QOL in individuals with type 2 diabetes (14,15). The current study is an ancillary analysis from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes (HART-D) trial (16). In this study, we attempted to further elucidate QOL outcomes by assessing changes in all QOL subscales measured on the Short-Form 36 Health Survey (SF-36) and compared SF-36 scores to U.S. national norms. Changes in QOL from preintervention to postintervention were compared across the four exercise conditions (aerobic only, resistance only, combined aerobic and resistance, and no-exercise control). We hypothesized that the resistance training group would demonstrate the greatest improvements in physical functioning QOL subscales, and that there would be no beneficial effects of exercise interventions on mental health QOL subscales.     

Empagliflozin as Add-on to Metformin Plus Sulfonylurea in Patients With Type 2 Diabetes: A 24-week,randomized, double-blind,placebo-controlled trial

OBJECTIVE

To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Patients inadequately controlled on metformin and sulfonylurea (HbA_1c ≥7 to ≤10%) were randomized and treated with once-daily empagliflozin 10 mg (n = 225), empagliflozin 25 mg (n = 216), or placebo (n = 225) for 24 weeks. The primary end point was change from baseline in HbA_1c at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24.

RESULTS

At week 24, adjusted mean (SE) changes from baseline in HbA_1c were −0.17% (0.05) for placebo vs. −0.82% (0.05) and −0.77% (0.05) for empagliflozin 10 and 25 mg, respectively (both P < 0.001). Empagliflozin significantly reduced MDG, weight, and systolic (but not diastolic) blood pressure versus placebo. Adverse events were reported in 62.7, 67.9, and 64.1% of patients on placebo and empagliflozin 10 and 25 mg, respectively. Events consistent with urinary tract infection were reported in 8.0, 10.3, and 8.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 13.3, 18.0, and 17.5%, respectively; males: 2.7, 2.7, and 0%, respectively). Events consistent with genital infection were reported in 0.9, 2.7, and 2.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 0.9, 4.5, and 3.9%, respectively; males: 0.9% in each group).

CONCLUSIONS

Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic control, weight, and systolic blood pressure and were well tolerated.Metformin is the standard first-line pharmacotherapy to achieve glycemic control in patients with type 2 diabetes (1). However, metformin alone frequently fails to maintain glycemic control in the long term (2), and most patients with type 2 diabetes will require additional therapies (1). Although initially effective, sulfonylureas are associated with low durability (2), and common side effects are hypoglycemia and weight gain (3–5). Furthermore, as type 2 diabetes progresses, with deterioration of β-cell function and increased insulin resistance (6), the use of agents utilizing pathways dependent on insulin becomes increasingly difficult. In addition, steady increases in weight are observed in patients with type 2 diabetes (7), which may be associated with worsening markers of insulin resistance (1). Thus, there is still a great unmet need for effective and well-tolerated antidiabetes agents that can be used in combination with existing treatments to improve glycemic control in patients with type 2 diabetes, in particular without the risk of hypoglycemia and weight gain.The sodium glucose cotransporter 2 (SGLT2), located in the proximal tubule of the kidney, represents a promising target for the treatment of type 2 diabetes. SGLT2 is responsible for tubular reabsorption of ∼90% of the glomerular filtrated glucose (8). In patients with type 2 diabetes, inhibition of SGLT2 leads to reduced renal glucose reabsorption and increased urinary glucose excretion, resulting in a reduction in hyperglycemia, irrespective of β-cell function or insulin resistance (9).Empagliflozin is a potent and selective inhibitor of SGLT2 (10). In phase II trials in patients with type 2 diabetes, a 12-week treatment with empagliflozin as monotherapy or as add-on to metformin resulted in reductions in HbA_1c, weight, and blood pressure and was well tolerated (11,12). These effects were shown to be sustained for up to 90 weeks (13).The aim of this study (EMPA-REG METSU) was to evaluate the efficacy, safety, and tolerability of empagliflozin (10 and 25 mg once daily) versus placebo over 24 weeks as add-on therapy to metformin plus sulfonylurea in patients with type 2 diabetes with inadequate glycemic control. In addition, the efficacy and safety of empagliflozin 25 mg was investigated in poorly controlled patients with HbA_1c >10% in an open-label treatment arm.     

Tramadol in post-herpetic neuralgia: a randomized,double-blind,placebo-controlled trial

The efficacy and safety of sustained-release tramadol compared to placebo in the treatment of post-herpetic neuralgia were evaluated in a multicenter, randomized, double-blind, parallel-group study in 127 outpatients. Treatment was administrated for 6 weeks. The dose of tramadol could be increased from 100 mg/day to 400 mg/day (300 mg/day in patients more than 75 years old). Groups were compared on changes in pain intensity on a Visual Analogue Scale (VAS) between inclusion and the 6th week of treatment (covariance analysis as main analysis and repeated measures analysis as complementary analysis) in the per protocol (PP) population. The randomized population comprised 127 patients aged 35-85 years, mostly females (72.4%). Groups were comparable at inclusion both in the intent to treat (ITT) population (63 patients in the tramadol group and 62 patients in the placebo group) and in the PP population (53 patients in the tramadol group and 55 patients in the placebo group). Mean pain intensity on day 43 adjusted on day 1 (covariance analysis) was significantly lower in the tramadol group than in the placebo group in both the PP (P=0.0499), and the ITT (P=0.031) populations. The two groups significantly differed on change in pain intensity over time (repeated measures analysis) in the ITT population (P=0.012). The percentage of pain relief over the 6th week was significantly higher in the tramadol group than in the placebo group (P=0.017). During the 6th week, patients in the tramadol group required less rescue medication than patients in the placebo group (P=0.022). No significant difference was found between groups either in pain intensity on a 5-point Verbal Scale (VRS) or in quality of life measurements. Tramadol was administered at an average dosage of 275.5 (89.7) mg/day after a 1-week dose-adaptation period. Tramadol was well tolerated. No notable difference appeared between groups either in the percentage of patients with treatment-associated adverse events (TAAE) (29.7% in the tramadol group and 31.8% in the placebo group) or in the total number of TAAE (31 in the tramadol group and 28 in the placebo group).     

A randomized, double-blind, placebo-controlled trial of Lessertia frutescens in healthy adults

Objectives:     

Physical Activity,Obesity, Nutritional Health and Quality of Life in Low-Income Hispanic Adults With Diabetes

The study examined relationships among age, body mass index (BMI), physical activity, nutritional health, quality of life, and health-related quality of life in Hispanic adults with diabetes (N = 59) using the PRECEDE-PROCEED planning model as a framework. Data were collected through face-to-face interviews at clinics and communities. A regression model with predisposing factors (age, BMI), and behavior (nutritional health and physical activity) significantly predicted quality of life (R ² = 0.21, F = 3.63, p < .05) explaining 21% of variance. Physical activity and nutrition were the strongest predictors. Culturally competent intervention strategies must include factors that improve and enhance quality of life.     

Effects of methylphenidate on fatigue and depression: a randomized, double-blind, placebo-controlled trial

ContextFatigue is highly prevalent in populations with advanced illness and is often associated with depressed mood. The role of psychostimulant therapy in the treatment of these conditions remains ill defined.ObjectivesTo evaluate the response of fatigue and depression in patients with advanced illness to titrated doses of methylphenidate (MP) as compared with placebo.MethodsIn a randomized, double-blind, placebo-controlled trial, 30 hospice patients, both inpatients and outpatients, who had fatigue scores of at least four on a scale of zero to 10 (0 = no fatigue and 10 = worst fatigue), were randomly assigned to receive either 5 mg of MP at 8 am and 1 pm or placebo. Doses of MP were titrated every three days according to response and adverse effects. Home care patients were monitored daily by telephone and visited by a research nurse on Study Days 0 (baseline), 3, 7, and 14. Fatigue was assessed using the Piper Fatigue Scale as the primary outcome measure and validated by the Visual Analogue Scale for Fatigue and the Edmonton Symptom Assessment Scale (ESAS) fatigue score. Subjects in inpatient facilities were interviewed or assessed by staff on an identical schedule. Depressive symptoms were assessed by the Beck Depression Inventory-II, Center for Epidemiologic Studies Depression Scale, and the ESAS depression score. Primary statistical analysis was conducted using repeated-measures multivariate analysis of the variance.ResultsBoth MP- and placebo-treated groups had similar measures of fatigue at baseline. Patients taking MP were found to have significantly lower fatigue scores (Piper Fatigue Scale, Visual Analogue Scale for Fatigue, and ESAS) at Day 14 compared with baseline. The improvement in fatigue with MP treatment was dose-dependent; the mean average effective dose was 10 mg on Day 3 and 20 mg on Day 14 (dose range of 10–40 mg). Placebo-treated individuals showed no significant improvement in fatigue. For patients with clinically significant depression on Day 0, treatment with MP was associated with a significant reduction in all test indices for depressed mood. For the placebo group, the changes in measures of depression were less than observed in the treatment group but were inconsistent between assessment tools. No significant toxicities were observed.ConclusionMP reduced symptoms of fatigue and depression when compared with placebo. The effect of MP on fatigue was dose-dependent and sustained over the duration of the study.     

A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis

BACKGROUND: Impaired mitochondrial phosphorylation potential may play a role in migraine pathogenesis. Metabolic enhancers, such as riboflavin or coenzyme Q, are effective in migraine prophylaxis and quasi-devoid of adverse effects. Thioctic acid (-lipoic acid) is another substance known to enhance energy metabolism in mitochondria and to be beneficial in diabetic neuropathy. OBJECTIVE: After an open pilot study suggesting its therapeutic antimigraine potentials, we embarked therefore in a randomized controlled trial of thioctic acid (Thioctacid) in migraine prophylaxis steered by the Belgian Headache Society. METHODS: Five Belgian centers recruited 54 migraineurs (43 migraine without aura, 11 with aura; mean age 38 +/- 8 years; 7 males). After a 1-month single-blinded run-in period, 44 patients received either placebo (n = 18) or thioctic acid 600 mg p.o./day (n = 26) for 3 months. RESULTS: Statistical analysis was carried out on an intention-to-treat basis. Monthly attack frequency tended to be reduced between run-in and the 3rd month of treatment in the thioctic acid group compared to placebo (P= .06). The proportion of 50% responders was not significantly different between thioctic acid (30.8%) and placebo (27.8%). Within-group analyses showed a significant reduction of attack frequency (P= .005), headache days (P= .009), and headache severity (P= .03) in patients treated with thioctic acid for 3 months, while these outcome measures remained unchanged in the placebo group. No adverse effects were reported. For logistical reasons this trial was interrupted before the planned 80 patients were enrolled. CONCLUSION: Albeit underpowered, this study tends to indicate that thioctic acid may be beneficial in migraine prophylaxis. Before any firm conclusion can be drawn, however, a large multicenter trial is necessary.     

Effect of "ionized" wrist bracelets on musculoskeletal pain: a randomized,double-blind,placebo-controlled trial

OBJECTIVE: To assess objectively the perceived benefits of wearing an "ionized" wrist bracelet to treat muscle or joint pain. SUBJECTS AND METHODS: This study was performed at the Mayo Clinic in Jacksonville, Fla, in 2000 and 2001. In a randomized, double-blind design, 305 participants wore an ionized bracelet and 305 wore a placebo bracelet for 4 weeks. For each location where pain was present at baseline, participants rated the intensity of pain. Follow-up ratings were made after 1, 3, 7, 14, 21, and 28 days of wearing the bracelet. Two primary end points were defined for evaluating efficacy. The first was the change at 4-week follow-up (day 28) in the pain score at the location with the highest baseline value (maximum pain score). The second was the change at 4-week follow-up in the sum of the pain scores for all locations. RESULTS: Analysis of the data showed significant improvement in pain scores in both groups, but no differences were observed between the group wearing the placebo bracelet and the group wearing the ionized bracelet. CONCLUSION: The finding that subjective improvement in pain scores was equivalent with ionized and placebo bracelet use questions the benefit of using an ionized bracelet. New treatments in alternative medical therapy must be shown to be effective through vigorous, unbiased, objective testing before physicians acknowledge potential benefits or recommend these treatments to patients.     

Remote electrical neuromodulation for migraine prevention: A double-blind,randomized, placebo-controlled clinical trial

Objective

To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.

Background

Preventive treatment is key to managing migraine, but it is often underutilized. REN, a non-pharmacological acute treatment for migraine, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, multi-center trial, with 1:1 ratio. The study consisted of a 4-week baseline observation phase, and an 8-week double-blind intervention phase in which participants used either REN or a placebo stimulation every other day. Throughout the study, participants reported their symptoms daily, via an electronic diary.

Results

Two hundred forty-eight participants were randomized (128 active, 120 placebo), of which 179 qualified for the modified intention-to-treat (mITT) analysis (95 active; 84 placebo). REN was superior to placebo in the primary endpoint, change in mean number of migraine days per month from baseline, with mean reduction of 4.0 ± SD of 4.0 days (1.3 ± 4.0 in placebo, therapeutic gain = 2.7 [confidence interval −3.9 to −1.5], p < 0.001). The significance was maintained when analyzing the episodic (−3.2 ± 3.4 vs. −1.0 ± 3.6, p = 0.003) and chronic (−4.7 ± 4.4 vs. −1.6 ± 4.4, p = 0.001) migraine subgroups separately. REN was also superior to placebo in reduction of moderate/severe headache days (3.8 ± 3.9 vs. 2.2 ± 3.6, p = 0.005), reduction of headache days of all severities (4.5 ± 4.1 vs. 1.8 ± 4.6, p < 0.001), percentage of patients achieving 50% reduction in moderate/severe headache days (51.6% [49/95] vs. 35.7% [30/84], p = 0.033), and reduction in days of acute medication intake (3.5 ± 4.1 vs. 1.4 ± 4.3, p = 0.001). Similar results were obtained in the ITT analysis. No serious device-related adverse events were reported in any group.

Conclusion

Applied every other day, REN is effective and safe for the prevention of migraine.     

Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113)

BACKGROUND: Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting. METHODS: One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks. Changes in limb fat between weeks 0 and 48 were measured using dual-energy Xray absorptiometry. Subcutaneous and visceral fat was measured by single-slice computed tomography; fasting plasma measurements of glucose, insulin and lipids levels were recorded. RESULTS: Limb fat increased by 0.38 kg in the pioglitazone group and 0.05 kg in the placebo group at week 48 (mean difference 0.33 kg, 95% confidence interval [CI] 0.10-0.56; P=0.051) by intention-to-treat analysis. In patients not receiving stavudine, an increase of 0.45 kg versus 0.04 kg was observed (mean difference, 0.40 kg, 95% CI 0.12-0.69; P=0.013), but this was not seen in patients on stavudine (n=36; P=0.404). Overall, there was no significant difference in subcutaneous abdominal fat or in visceral fat areas on computed tomography at L4 vertebra. The lipid profile was not significantly different at week 48 except for levels of high-density lipoprotein cholesterol, which was improved in the pioglitazone group (+0.08 mmol/l versus -0.08; P=0.005). CONCLUSIONS: Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients. Treatment did lead to a favourable lipid profile, however, suggesting that this thiazolidinedione should be considered in the context of HIV-related lipoatrophy.     

Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents. Patients and Methods.— In this double‐blind, placebo‐controlled, parallel‐group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints. Results.— The 2‐hour pain‐relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2‐hour pain‐relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25‐ and 12.5‐mg doses and P < .05 for the 25‐mg dose. Age group subanalysis demonstrated significantly greater 2‐hour pain‐relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence. Conclusions.— Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5‐mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.     

The Effects of a Mindfulness-Based Intervention on Emotional Distress,Quality of Life,and HbA1c in Outpatients With Diabetes (DiaMind): A randomized controlled trial

OBJECTIVE

Emotional distress is common in outpatients with diabetes, affecting ∼20–40% of the patients. The aim of this study was to determine the effectiveness of group therapy with Mindfulness-Based Cognitive Therapy (MBCT), relative to usual care, for patients with diabetes with regard to reducing emotional distress and improving health-related quality of life and glycemic control.

RESEARCH DESIGN AND METHODS

In the present randomized controlled trial, 139 outpatients with diabetes (type 1 or type 2) and low levels of emotional well-being were randomized to MBCT (n = 70) or a waiting list group (n = 69). Primary outcomes were perceived stress (Perceived Stress Scale), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), mood (Profiles of Mood States), and diabetes-specific distress (Problem Areas In Diabetes). Secondary outcomes were health-related quality of life (12-Item Short-Form Health Survey), and glycemic control (HbA_1c). Assessments were conducted at baseline and at 4 and 8 weeks of follow-up.

RESULTS

Compared with control, MBCT was more effective in reducing stress (P < 0.001, Cohen d = 0.70), depressive symptoms (P = 0.006, d = 0.59), and anxiety (P = 0.019, d = 0.44). In addition, MBCT was more effective in improving quality of life (mental: P = 0.003, d = 0.55; physical: P = 0.032, d = 0.40). We found no significant effect on HbA_1c or diabetes-specific distress, although patients with elevated diabetes distress in the MBCT group tended to show a decrease in diabetes distress (P = 0.07, d = 0.70) compared with the control group.

CONCLUSIONS

Compared with usual care, MBCT resulted in a reduction of emotional distress and an increase in health-related quality of life in diabetic patients who had lower levels of emotional well-being.Emotional distress, which can consist of symptoms of depression, anxiety, and diabetes-specific distress affects ∼20 to 40% of outpatients with type 1 or type 2 diabetes (1–3), making it a common comorbid health problem in these patients. Emotional distress results in lower quality of life (4) and more negative appraisals of insulin therapy (5). In addition, depression is associated with suboptimal self-care behaviors (6), suboptimal glycemic control (7), adverse cardiovascular outcomes, and higher mortality rates (8,9). Although the emotional problems in diabetic patients have received increasing attention in the last decade, they are still often not recognized in clinical practice and remain untreated (10).Previous research has shown that antidepressant medication and cognitive behavioral therapy are effective treatments for major depression in diabetic patients (11,12). However, the use of antidepressant medication is often accompanied by serious side effects, and a substantial percentage of the patients (∼30–50%) still do not respond to treatment or they relapse (13). Hence, we need to conduct new studies testing new treatments for emotional distress in diabetes. Because the number of diabetic patients is rapidly increasing, we need to develop interventions that are not only effective but also affordable. Web-based therapies and group therapies are good candidates.One easily accessible group intervention that proved successful in reducing emotional distress and improving quality of life in nonpatients and in diverse patient groups (14–16) is Mindfulness-Based Cognitive Therapy (MBCT) (17). MBCT is an 8-week protocolized group therapy program that combines meditation exercises with elements of cognitive therapy. The central component of this intervention is the cultivation of mindfulness. This can be defined as the self-regulation of one’s attention focusing on direct experience, while adopting a curious, open, and accepting attitude toward these experiences, especially one’s psychological processes, such as thoughts and feelings (18). A recent meta-analysis has shown medium- to large-effect sizes for mindfulness-based interventions in reducing symptoms of anxiety and depression (19).Two other studies examined the effect of a mindfulness-based intervention on emotional distress in people with diabetes (20,21). In one uncontrolled study, the mindfulness group showed a significant decrease in depressive symptoms at postintervention and in HbA_1c at the 1-month follow-up (20). The other study found no significant effects directly after the intervention, but significant improvements in depressive symptoms (Cohen d = 0.71) and mental health–related quality of life (d = 0.54) were reported at the 1-year follow-up (21). The results of these studies are in line with the notion that mindfulness-based interventions could be adequate in reducing emotional problems in people with diabetes. However, the presence of emotional distress was not an inclusion criterion in either study, and only the latter study was a randomized controlled trial (21).Studies testing the effectiveness of a mindfulness-based intervention in outpatients with type 1 diabetes are still lacking. Therefore, the purpose of the current study was to test the effectiveness of MBCT for people with type 1 or type 2 diabetes and comorbid emotional distress. The primary outcome was the effect on emotional distress, including symptoms of depression, anxiety, diabetes-specific distress, and general perceived stress. Secondary outcomes were health-related quality of life and glycemic control. From the results of two systematic reviews (19,22), we hypothesized that after MBCT, diabetic patients would experience significant greater reductions in emotional distress compared with a waiting list control group. We also hypothesized that MBCT would lead to better health-related quality of life and lower HbA_1c.     

Effects of perioperative rosuvastatin on postoperative delirium in elderly patients: A randomized,double-blind,and placebo-controlled trial

BACKGROUNDExperimental evidence has indicated the benefits of statins for the treatment of postoperative delirium. Previously, clinical trials did not reach definite conclusions on the effects of statins on delirium. Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes, while some studies have reported negative results.AIMTo evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.METHODSThis randomized, double-blind, and placebo-controlled trial was conducted in a single center in Jiangsu, China. This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either rosuvastatin (40 mg/d) or placebo. Participants, care providers, and investigators were all masked to group assignments. The primary endpoint was the incidence of delirium, which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days. Analyses were performed on intention-to-treat and safety populations.RESULTSBetween January 1, 2017 and January 1, 2020, 3512 patients were assessed. A total of 821 patients were randomly assigned to receive either placebo (n = 411) or rosuvastatin (n = 410). The incidence of postoperative delirium was significantly lower in the rosuvastatin group [23 (5.6%) of 410 patients] than in the placebo group {42 (13.5%) of 411 patients [odds ratios (OR) = 0.522, 95% confidence interval (CI): 0.308-0.885; P < 0.05]}. No significant difference in 30-d all-cause mortality (6.1% vs 8.7%, OR = 0.67, 95%CI: 0.39-1.2, P = 0.147) was observed between the two groups. Rosuvastatin decreased the hospitalization time (13.8 ± 2.5 vs 14.2 ± 2.8, P = 0.03) and hospitalization expenses (9.3 ± 2.5 vs 9.8 ± 2.9, P = 0.007). No significant differences in abnormal liver enzymes (9.0% vs 7.1%, OR = 1.307, 95%CI: 0.787-2.169, P = 0.30) or rhabdomyolysis (0.73% vs 0.24%, OR = 3.020, 95%CI: 0.31-29.2, P = 0.37) were observed between the two groups.CONCLUSIONThe current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia. However, the evidence does not reveal that rosuvastatin improves clinical outcomes. The therapy is safe. Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.