Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence

Objective: Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence. Methods: We carried out a randomized controlled, open-label trial comparing rapid opiate detoxification under anesthesia and naltrexone treatment with continued methadone maintenance at the Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, Australia. The study subjects were patients stabilized on methadone maintenance treatment for heroin dependence who wished to transfer to naltrexone treatment. The Beck Depression Inventory, State-Trait Anxiety Inventory and Opiate Treatment Index subscales for heroin use and social functioning were used at baseline and follow-up assessments at 1, 2, 3 and 6 months. Results: Forty-two participants were allocated to receive naltrexone treatment, whereas 38 continued methadone maintenance as the control condition. Participants who received naltrexone did not exhibit worsening of depressive symptoms. In participants attending all follow-up assessments, there was a trend for those receiving naltrexone to exhibit an improvement in depression over time compared with the control group. Participants who were adherent to naltrexone treatment exhibited fewer depressive symptoms than those who were nonadherent. Conclusions: These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms.

Creative credits:a randomized controlled industrial policy experiment

This report examines the results of a pilot study, which used a method of evaluation called randomised control trials (RCTs) to see if a popular business support scheme called Creative Credits worked effectively. The pilot study, which began in Manchester in 2009, was structured so that vouchers, or 'Creative Credits', would be randomly allocated to small and medium-sized businesses applying to invest in creative projects such as developing websites, video production and creative marketing campaigns, to see if they had a real effect on innovation. The research found that the firms who were awarded Creative Credits enjoyed a short-term boost in their innovation and sales growth in the six months following completion of their creative projects. However, the positive effects were not sustained, and after 12 months there was no longer a statistically significant difference between the groups that received the credits and those that didn’t. The report argues that these results would have remained hidden using the normal evaluation methods used by government, and calls for RCTs to be used more widely when evaluating policies to support business growth.

Pronounced reduction of postprandial glucagon by lixisenatide:a meta-analysis of randomized clinical trials

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice.

Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333)

Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3-30 days post ischaemic stroke into a phase II randomised (1:1), double blind, placebo-controlled trial. Subjects received dexamphetamine (5mg initially, then 10mg for 10 subsequent doses with 3 or 4 day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl-Meyer, FM), and functional scales (Barthel index, BI and modified Rankin score, mRS). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 minutes after, the first 2 doses. 33 subjects were recruited, age 33-88 (mean 71) years, males 52%, 4-30 (median 15) days post stroke to inclusion. 16 patients were randomised to placebo and 17 amphetamine. Amphetamine did not improve motor function at 90 days; mean (standard deviation) FM 37.6 (27.6) vs. control 35.2 (27.8) (p=0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate, were 11.2 mmHg (p=0.03), 9.5 mmHg (p=0.04) and 7 beats/minute (p=0.02) higher respectively with amphetamine, compared with control. A non-significant reduction in myocardial perfusion (Buckberg Index) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and heart rate without altering cerebral haemodynamics.

Association Of Lipophilic Opioids And Hyperbaric Bupivacaine In Spinal Anesthesia For Elective Cesarean Section. Randomized Controlled Study.

To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section. A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25 µg) and GS - sufentanil (5.0 µg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level. The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy. The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil.

Transcutaneous Tibial Nerve Stimulation In The Treatment Of Lower Urinary Tract Symptoms And Its Impact On Health-related Quality Of Life In Patients With Parkinson Disease: A Randomized Controlled Trial.

A randomized controlled trial study was performed to evaluate the efficacy of transcutaneous tibial nerve stimulation (TTNS) and sham TTNS, in patients with Parkinson disease (PD) with lower urinary tract symptoms (LUTS). Randomized controlled trial. Thirteen patients with a diagnosis of PD and bothersome LUTS were randomly allocated to one of the following groups: Group I: TTNS group (n = 8) and group II: Sham group (n = 5). Both groups attended twice a week during 5 weeks; each session lasted 30 minutes. Eight patients received TTNS treatment and 5 subjects allocated to group II were managed with sham surface electrodes that delivered no electrical stimulation. Assessments were performed before and after the treatment; they included a 3-day bladder diary, Overactive Bladder Questionnaire (OAB-V8), and the International Consultation on Incontinence Quality of Life Questionnaire Short Form (ICIQ-SF), and urodynamic evaluation. Following 5 weeks of treatment, patients allocated to TTNS demonstrated statistically significant reductions in the number of urgency episodes (P = .004) and reductions in nocturia episodes (P < .01). Participants allocated to active treatment also showed better results after treatment in the OAB-V8 and ICIQ-SF scores (P < .01, respectively). Urodynamic testing revealed that patients in the active treatment group showed improvements in intravesical volume at strong desire to void (P < .05) and volume at urgency (P < .01) when compared to subjects in the sham treatment group. These findings suggest that TTNS is effective in the treatment of LUTS in patients with PD, reducing urgency and nocturia episodes and improving urodynamic parameters as well as symptom scores measured by the OAB-V8 and health-related quality-of-life scores measured by the ICIQ-SF.

Two-dimensional Ultrasound And Ultrasound Elastography Imaging Of Trigger Points In Women With Myofascial Pain Syndrome Treated By Acupuncture And Electroacupuncture: A Double-blinded Randomized Controlled Pilot Study.

Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects.

[comparative Study Between Fast And Slow Induction Of Propofol Given By Target-controlled Infusion: Expected Propofol Concentration At The Effect Site. Randomized Controlled Trial].

studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-μg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1μg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0μg.ml(-1)) at Es, and waited until loss of consciousness. in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56μg.mL(-1), respectively, p=0.004). the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

INTRODUCTION: Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. OBJECTIVE: The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. MATERIAL AND METHODS: Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. RESULTS: The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. CONCLUSIONS: The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement.

Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults

The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used

Effects of Low-Level Laser Therapy on Pain and Scar Formation After Inguinal Herniation Surgery: A Randomized Controlled Single-Blind Study

Objective: The aim of this study was to investigate the efficacy of an infrared GaAlAs laser operating with a wavelength of 830 nm in the postsurgical scarring process after inguinal-hernia surgery. Background: Low-level laser therapy (LLLT) has been shown to be beneficial in the tissue-repair process, as previously demonstrated in tissue culture and animal experiments. However, there is lack of studies on the effects of LLLT on postsurgical scarring of incisions in humans using an infrared 830-nm GaAlAs laser. Method: Twenty-eight patients who underwent surgery for inguinal hernias were randomly divided into an experimental group (G1) and a control group (G2). G1 received LLLT, with the first application performed 24 h after surgery and then on days 3, 5, and 7. The incisions were irradiated with an 830-nm diode laser operating with a continuous power output of 40 mW, a spot-size aperture of 0.08 cm(2) for 26 s, energy per point of 1.04 J, and an energy density of 13 J/cm(2). Ten points per scar were irradiated. Six months after surgery, both groups were reevaluated using the Vancouver Scar Scale (VSS), the Visual Analog Scale, and measurement of the scar thickness. Results: G1 showed significantly better results in the VSS totals (2.14 +/- 1.51) compared with G2 (4.85 +/- 1.87); in the thickness measurements (0.11 cm) compared with G2 (0.19 cm); and in the malleability (0.14) compared with G2 (1.07). The pain score was also around 50% higher in G2. Conclusion: Infra-red LLLT (830 nm) applied after inguinal-hernia surgery was effective in preventing the formation of keloids. In addition, LLLT resulted in better scar appearance and quality 6 mo postsurgery.

Perineal Analgesia With an Ice Pack After Spontaneous Vaginal Birth: A Randomized Controlled Trial

Methods: We conducted a randomized controlled trial at the Amparo Maternal Birth Center in Sao Paulo, Brazil. Study participants included 114 nulliparous women divided into 3 groups (n = 38 per group): experimental (ice packs on the perineum), placebo (water packs at set temperature), and control (no treatment). Results: A numerical scale (0 to 10) was used for pain assessment. A comparison of the average pain at the beginning and after 20 minutes showed a significant reduction of pain (P < .001) in the 3 groups, and the experimental group had a lower average score for pain compared with the control group (1.6 versus 3.3, P = .032). Discussion: The use of ice packs for 20 minutes was effective for perineal pain relief after vaginal birth.