Manual therapy followed by specific active exercises versus a placebo followed by specific active exercises on the improvement of functional disability in patients with chronic non specific low back pain: a randomized controlled trial.

BACKGROUND: Recent clinical recommendations still propose active exercises (AE) for CNSLBP. However, acceptance of exercises by patients may be limited by pain-related manifestations. Current evidences suggest that manual therapy (MT) induces an immediate analgesic effect through neurophysiologic mechanisms at peripheral, spinal and cortical levels. The aim of this pilot study was first, to assess whether MT has an immediate analgesic effect, and second, to compare the lasting effect on functional disability of MT plus AE to sham therapy (ST) plus AE. METHODS: Forty-two CNSLBP patients without co-morbidities, randomly distributed into 2 treatment groups, received either spinal manipulation/mobilization (first intervention) plus AE (MT group; n = 22), or detuned ultrasound (first intervention) plus AE (ST group; n = 20). Eight therapeutic sessions were delivered over 4 to 8 weeks. Immediate analgesic effect was obtained by measuring pain intensity (Visual Analogue Scale) before and immediately after the first intervention of each therapeutic session. Pain intensity, disability (Oswestry Disability Index), fear-avoidance beliefs (Fear-Avoidance Beliefs Questionnaire), erector spinae and abdominal muscles endurance (Sorensen and Shirado tests) were assessed before treatment, after the 8th therapeutic session, and at 3- and 6-month follow-ups. RESULTS: Thirty-seven subjects completed the study. MT intervention induced a better immediate analgesic effect that was independent from the therapeutic session (VAS mean difference between interventions: -0.8; 95% CI: -1.2 to -0.3). Independently from time after treatment, MT + AE induced lower disability (ODI mean group difference: -7.1; 95% CI: -12.8 to -1.5) and a trend to lower pain (VAS mean group difference: -1.2; 95% CI: -2.4 to -0.30). Six months after treatment, Shirado test was better for the ST group (Shirado mean group difference: -61.6; 95% CI: -117.5 to -5.7). Insufficient evidence for group differences was found in remaining outcomes. CONCLUSIONS: This study confirmed the immediate analgesic effect of MT over ST. Followed by specific active exercises, it reduces significantly functional disability and tends to induce a larger decrease in pain intensity, compared to a control group. These results confirm the clinical relevance of MT as an appropriate treatment for CNSLBP. Its neurophysiologic mechanisms at cortical level should be investigated more thoroughly. TRIAL REGISTRATION: Trial registration number: NCT01496144.

Universal screening and decolonization for control of MRSA in nursing homes : a cluster randomized controlled study

OBJECTIVE The risk of carrying methicillin-resistant Staphylococcus aureus (MRSA) is higher among nursing home (NH) residents than in the general population. However, control strategies are not clearly defined in this setting. In this study, we compared the impact of standard precautions either alone (control) or combined with screening of residents and decolonization of carriers (intervention) to control MRSA in NHs. DESIGN Cluster randomized controlled trial SETTING NHs of the state of Vaud, Switzerland PARTICIPANTS Of 157 total NHs in Vaud, 104 (67%) participated in the study. INTERVENTION Standard precautions were enforced in all participating NHs, and residents underwent MRSA screening at baseline and 12 months thereafter. All carriers identified in intervention NHs, either at study entry or among newly admitted residents, underwent topical decolonization combined with environmental disinfection, except in cases of MRSA infection, MRSA bacteriuria, or deep skin ulcers. RESULTS NHs were randomly allocated to a control group (51 NHs, 2,412 residents) or an intervention group (53 NHs, 2,338 residents). Characteristics of NHs and residents were similar in both groups. The mean screening rates were 86% (range, 27%-100%) in control NHs and 87% (20%-100%) in intervention NHs. Prevalence of MRSA carriage averaged 8.9% in both control NHs (range, 0%-43%) and intervention NHs (range, 0%-38%) at baseline, and this rate significantly declined to 6.6% in control NHs and to 5.8% in intervention NHs after 12 months. However, the decline did not differ between groups (P=.66). CONCLUSION Universal screening followed by decolonization of carriers did not significantly reduce the prevalence of the MRSA carriage rate at 1 year compared with standard precautions

Basal and stimulated lactate fluxes in primary cultures of astrocytes are differentially controlled by distinct proteins.

Lactate release by astrocytes is postulated to be of importance for neuroenergetics but its regulation is poorly understood. Basigin, a chaperone protein for specific monocarboxylate transporters (MCTs), represents a putatively important regulatory element for lactate fluxes. Indeed, basigin knockdown by RNA interference in primary cultures of astrocytes partially reduced both proton-driven lactate influx and efflux. But more strikingly, enhancement of lactate efflux induced by glutamate was prevented while the effect of sodium azide was significantly reduced by treatment of cultured astrocytes with anti-basigin small interfering RNA. Enhancement of glucose utilization was unaffected under the same conditions. Basal lactate uptake and release were significantly reduced by MCT1 knockdown, even more so than with basigin knockdown, whereas glutamate-driven or sodium azide-induced enhancement of lactate release was not inhibited by either MCT1, 2, or 4 small interfering RNAs. In conclusion, MCT1 plays a pivotal role in the control of basal proton-driven lactate flux in astrocytes while basigin is only partly involved, most likely via its interaction with MCT1. In contrast, basigin appears to critically regulate the enhancement of lactate release caused by glutamate (or sodium azide) but via an effect on another unidentified transporter at least present in astrocytes in vitro.

The Impact of CAROtid plaque Screening on Smoking (CAROSS) cessation and control of other cardiovascular risk factors: rationale and design of a randomized controlled trial

BACKGROUND: Screening tests for subclinical cardiovascular disease, such as markers of atherosclerosis, are increasingly used in clinical prevention to identify individuals at high cardiovascular risk. Being aware of these test results might also enhance patient motivation to change unhealthy behaviors but the effectiveness of such a screening strategy has been poorly studied. METHODS: The CAROtid plaque Screening trial on Smoking cessation (CAROSS) is a randomized controlled trial in 530 regular smokers aged 40-70 years to test the hypothesis that carotid plaque screening will influence smokers' behavior with an increased rate of smoking cessation (primary outcome) and an improved control of other cardiovascular risk factors (secondary outcomes) after 1-year follow-up. All smokers will receive a brief advice for smoking cessation,and will subsequently be randomly assigned to either the intervention group (with plaques screening) or the control group (without plaque screening). Carotid ultrasound will be conducted with a standard protocol. Smokers with at least one carotid plaque will receive pictures of their own plaques with a structured explanation on the general significance of plaques. To ensure equal contact conditions, smokers not undergoing ultrasound and those without plaque will receive a relevant explanation on the risks associated with tobacco smoking. Study outcomes will be compared between smokers randomized to plaque screening and smokers not submitted to plaque screening. SUMMARY: This will be the first trial to assess the impact of carotid plaque screening on 1-year smoking cessation rates and levels of control of other cardiovascular risk factors.

Influence of counselor characteristics and behaviors on the efficacy of a brief motivational intervention for heavy drinking in young men-a randomized controlled trial.

BACKGROUND: Brief motivational intervention (BMI) has shown promising results to reduce alcohol use in young adults. Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation. Particularly, little attention has been given to counselor influence on treatment mechanisms. METHODS: We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men (age 20) screened as hazardous drinkers. Participants were randomly allocated to (i) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics (gender, professional status, clinical experience, and motivational interviewing [MI] experience) or (ii) a control group receiving assessment only. Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy. Then, the influence of counselors' characteristics (i.e., gender, professional status, clinical experience, MI experience, BMI attitudes, and expectancies) and within-session behaviors (i.e., measured by the Motivational Interviewing Skill Code) on outcome was tested in regression analyses. RESULTS: There was a significant (p = 0.02) decrease in alcohol use among the BMI group compared to the control group. Counselors that were male, more experienced, that had more favorable BMI attitudes and expectancies, higher MI skills, but surprisingly less MI-consistent behaviors, had significantly better outcomes than the control group while their counterparts did not. CONCLUSIONS: The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males. Moreover, BMI effect was related to interindividual differences among counselors, and results therefore provide recommendations for BMI training and implementation with similar populations.

Use of nicotine substitute prescribed at hourly plus ab libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial.

OBJECTIVE: To assess the impact of instructional guidance in the regular use of use nicotine nasal spray (NNS) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit. METHODS: This randomized, open, controlled trial included 50 patients who were heavy smokers, were willing to quit, and attending an academic outpatient clinic in Western Switzerland. Patients were randomised to instruction on NNS use as "ad libitum" (administration whenever cravings appear; control group) or to use NNS when craving appears and at least every hour when awake (intervention group). Intakes were monitored using an electronic device fixed in the spray unit (MDILog) during the first three weeks of use. Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide. Using intention-to-treat analysis, random-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual. RESULTS: One patient was lost to follow-up. At baseline randomization, the group receiving instruction to use NNS hourly included more women, patients with previous desires to quit, and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings (group imbalance). Both groups self-administered more than the daily recommended dosage of 8 uses. Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings, respectively. Adjusting for baseline imbalance, the increased daily doses in the intervention group (hourly use) remained nonsignificant compared to ad libitum use (-0.5 dose/day; CI 95% -6.2; 5.3, from day 1 to day 7; and 2.3 dose/day; CI 95% -5.4; 10.0, from day 8 to day 21). Instructing patients to use the NNS daily had no effect on smoking cessation at six months (RR = 0.69; CI 95% 0.34; 1.39). CONCLUSION: Heavy smokers willing to quit use NNS frequently, regardless of the instructions given. Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00861276.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Adalimumab in Severe and Acute Sciatica (ASAS) : a multicentre, randomized, double-blind, placebo-controlled trial : 1240

Background Based on several experimental results and on a preliminary study, a trial was undertaken to assess the efficacy of adalimumab, a TNF-α inhibitor, in patients with radicular pain due to lumbar disc herniation. Methods A multicentre, double-blind, randomised controlled trial was conducted between May 2005 and December 2007 in Switzerland. Patients with acute (< 12 weeks) and severe (Oswestry Disability index > 50) radicular leg pain and imaging-confirmed lumbar disc herniation were randomised to receive as adjuvant therapy either two subcutaneous injections of adalimumab (40 mg) at 7 days interval or matching placebo. The primary outcome was leg pain, which was recorded every day for 10 days and at 6-weeks and 6- months based on a visual analogue scale (0 to 100). Results Of the 265 patients screened, 61 were enrolled (adalimumab= 31) and 4 were lost to follow-up. Over time, the evolution of leg pain was more favourable in the adalimumab group than in the placebo group (p<0.001). However, the effect size was relatively small and at last follow-up the difference was 13.8 (CI95% -11.5 - 39.0). In the adalimumab group twice as many patients fulfilled the criteria for "responders" and for "low residual disease impact" ( p<0.05) and fewer surgical discectomies were performed (6 versus 13, p=0.04). Conclusion The addition of a short course of adalimumab to the treatment regimen of patients suffering from acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures.

A randomized controlled trial of the effectiveness of a Computer-Assisted Cognitive Remediation (CACR) program in adolescents with psychosis or at high risk of psychosis: Short term and long term outcomes

The present study investigates the short- and long-term outcomes of a computer-assisted cognitive remediation (CACR) program in adolescents with psychosis or at high risk. 32 adolescents participated in a blinded 8-week randomized controlled trial of CACR treatment compared to computer games (CG). Clinical and neuropsychological evaluations were undertaken at baseline, at the end of the program and at 6-month. At the end of the program (n = 28), results indicated that visuospatial abilities (Repeatable Battery for the Assessment of Neuropsychological Status, RBANS; P = .005) improved signifi cantly more in the CACR group compared to the CG group. Furthermore, other cognitive functions (RBANS), psychotic symptoms (Positive and Negative Symptom Scale) and psychosocial functioning (Social and Occupational Functioning Assessment Scale) improved signifi cantly, but at similar rates, in the two groups. At long term (n = 22), cognitive abilities did not demonstrated any amelioration in the control group while, in the CACR group, signifi cant long-term improvements in inhibition (Stroop; P = .040) and reasoning (Block Design Test; P = .005) were observed. In addition, symptom severity (Clinical Global Improvement) decreased signifi cantly in the control group (P = .046) and marginally in the CACR group (P = .088). To sum up, CACR can be successfully administered in this population. CACR proved to be effective over and above CG for the most intensively trained cognitive ability. Finally, on the long-term, enhanced reasoning and inhibition abilities, which are necessary to execute higher-order goals or to adapt behavior to the ever-changing environment, were observed in adolescents benefi ting from a CACR.

Effect of a national primary care pay for performance scheme on emergency hospital admissions for ambulatory care sensitive conditions: controlled longitudinal study.

OBJECTIVE: To estimate the impact of a national primary care pay for performance scheme, the Quality and Outcomes Framework in England, on emergency hospital admissions for ambulatory care sensitive conditions (ACSCs). DESIGN: Controlled longitudinal study. SETTING: English National Health Service between 1998/99 and 2010/11. PARTICIPANTS: Populations registered with each of 6975 family practices in England. MAIN OUTCOME MEASURES: Year specific differences between trend adjusted emergency hospital admission rates for incentivised ACSCs before and after the introduction of the Quality and Outcomes Framework scheme and two comparators: non-incentivised ACSCs and non-ACSCs. RESULTS: Incentivised ACSC admissions showed a relative reduction of 2.7% (95% confidence interval 1.6% to 3.8%) in the first year of the Quality and Outcomes Framework compared with ACSCs that were not incentivised. This increased to a relative reduction of 8.0% (6.9% to 9.1%) in 2010/11. Compared with conditions that are not regarded as being influenced by the quality of ambulatory care (non-ACSCs), incentivised ACSCs also showed a relative reduction in rates of emergency admissions of 2.8% (2.0% to 3.6%) in the first year increasing to 10.9% (10.1% to 11.7%) by 2010/11. CONCLUSIONS: The introduction of a major national pay for performance scheme for primary care in England was associated with a decrease in emergency admissions for incentivised conditions compared with conditions that were not incentivised. Contemporaneous health service changes seem unlikely to have caused the sharp change in the trajectory of incentivised ACSC admissions immediately after the introduction of the Quality and Outcomes Framework. The decrease seems larger than would be expected from the changes in the process measures that were incentivised, suggesting that the pay for performance scheme may have had impacts on quality of care beyond the directly incentivised activities.

Psychodynamic psychotherapy in newly diagnosed cancer patients: a randomized controlled trial

Aims: (i) To describe the prevalence and profile of newly diagnosed cancer patients motivated for psychotherapy and (ii) To evaluate its effectiveness.Methods: Between 2006 and 2009, every new patient of the Oncology Service of the University Hospital Lausanne was informed of the opportunity to benefit from psychotherapeutic support. Patients were randomly assigned to an immediate or delayed (4 month waiting list) psychodynamicoriented psychotherapeutic intervention, formalized as short intervention (1-4 sessions) or brief psychotherapy (16 sessions). Patients with no interest were asked to participate in an observational group. Socio-demographic and medical data, anxiety and depression (HADS, SCL-90), alexithymia (TAS) and quality of life were evaluated for all groups at baseline and 1, 4, 8 and 12-months follow-up. Results: Of 1973 patients approached, 1024 were excluded, mainly because of organisational reasons (living too far away, interfering treatments, etc.), ageN75 years, life expectancyb1 year or language difficulties. One fourth (N=530) refused to participate and 229 patients accepted to be followed in the observational group. Patients interested in psychological support (N=190, 94 in immediate and 96 in delayed intervention) were younger, predominantly female and symptomatic (higher depression and anxiety scores); 56% engaged in 1-4 and 44% in 16 sessions.Conclusions: The naturalistic design of this study revealed relevant questions regarding (i) the design of such studies (untargeted intervention, choice of measurement, etc.), (ii) the type of interventions (pro-active approaches of men, those unable to speak the language or who can not leave home) and (iii) the profile of patients accepting support. A complete analysis will be presented at the congress.Keywords: Psychotherapy, psycho-oncology, cancer, methodology, interventions

Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. RESULTS: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

A controlled trial of the benefits of ultrasound-guided steroid injection for shoulder pain.

OBJECTIVES: We studied the value of ultrasound (US) to define shoulder pathology and guide local steroid injection in comparison with a standard injection in the management of the acute painful shoulder. METHODS: Seventy consecutive patients with acute shoulder pain were assessed clinically and by US. Patients were randomized to receive either a standard subacromial infiltration of 7 mg of betamethasone or a US-guided injection according to the US diagnosis. Follow-up evaluations were performed by an independent assessor who was blinded to the results of the initial US and clinical assessments. RESULTS: Sixty-seven patients completed the study. Both groups showed a significant reduction in both daytime and night pain compared to baseline. The US injection group had significantly less pain at rest at 2 and 6 weeks (NRS: 1.6 vs 3.3, P<0.005; 3 vs 4.2, P<0.04). The percentage of good responders was significantly higher in US group at 2 weeks, (81% vs 54%, P<0.005) and 6 weeks (64% vs 38%, P<0.05). At 2 and 6 weeks, responder rate and activity pain scores as well as Constant score were in favour of US, though did not reach statistical significance. CONCLUSION: Local steroid injection for shoulder pain leads to significant improvements in pain and function for up to 12 weeks. An US examination to define the origin of shoulder pain as well as to guide injection provides significant additional benefits for up to 6 weeks. We recommend routine US examination as part of the management of acute shoulder pain.

Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions.

OBJECTIVES: Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0-100 mm visual analogue scale and time to first new flare. METHODS: Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). RESULTS: 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count. CONCLUSION: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.