Efficacy and safety of acupuncture for the treatment of non-specific acute low back pain: a randomised controlled multicentre trial protocol [ISRCTN65814467]

BACKGROUND Low back pain and its associated incapacitating effects constitute an important healthcare and socioeconomic problem, as well as being one of the main causes of disability among adults of working age. The prevalence of non-specific low back pain is very high among the general population, and 60-70% of adults are believed to have suffered this problem at some time. Nevertheless, few randomised clinical trials have been made of the efficacy and efficiency of acupuncture with respect to acute low back pain. The present study is intended to assess the efficacy of acupuncture for acute low back pain in terms of the improvement reported on the Roland Morris Questionnaire (RMQ) on low back pain incapacity, to estimate the specific and non-specific effects produced by the technique, and to carry out a cost-effectiveness analysis. METHODS/DESIGN Randomised four-branch controlled multicentre prospective study made to compare semi-standardised real acupuncture, sham acupuncture (acupuncture at non-specific points), placebo acupuncture and conventional treatment. The patients are blinded to the real, sham and placebo acupuncture treatments. Patients in the sample present symptoms of non specific acute low back pain, with a case history of 2 weeks or less, and will be selected from working-age patients, whether in paid employment or not, referred by General Practitioners from Primary Healthcare Clinics to the four clinics participating in this study. In order to assess the primary and secondary result measures, the patients will be requested to fill in a questionnaire before the randomisation and again at 3, 12 and 48 weeks after starting the treatment. The primary result measure will be the clinical relevant improvement (CRI) at 3 weeks after randomisation. We define CRI as a reduction of 35% or more in the RMQ results. DISCUSSION This study is intended to obtain further evidence on the effectiveness of acupuncture on acute low back pain and to isolate the specific and non-specific effects of the treatment.

Study protocol for a pragmatic randomised controlled trial in general practice investigating the effectiveness of acupuncture against migraine.

BACKGROUND Migraine is a chronic neurologic disease that can severely affect the patient's quality of life. Although in recent years many randomised studies have been carried out to investigate the effectiveness of acupuncture as a treatment for migraine, it remains a controversial issue. Our aim is to determine whether acupuncture, applied under real conditions of clinical practice in the area of primary healthcare, is more effective than conventional treatment. METHODS/DESIGN The design consists of a pragmatic multi-centre, three-armed randomised controlled trial, complemented with an economic evaluation of the results achieved, comparing the effectiveness of verum acupuncture with sham acupuncture, and with a control group receiving normal care only. Patients eligible for inclusion will be those presenting in general practice with migraine and for whom their General Practitioner (GP) is considering referral for acupuncture. Sampling will be by consecutive selection, and by randomised allocation to the three branches of the study, in a centralised way following a 1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment). Secondly, one patient in three will be randomly selected from each of the acupuncture (verum or sham) groups for a brain perfusion study (by single photon emission tomography). The treatment with verum acupuncture will consist of 8 treatment sessions, once a week, at points selected individually by the acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, with treatment being applied at non-acupuncture points in the dorsal and lumbar regions, using the minimal puncture technique. The control group will be given conventional treatment, as will the other two groups. DISCUSSION This trial will contribute to available evidence on acupuncture for the treatment of migraine. The primary endpoint is the difference in the number of days with migraine among the three groups, between the baseline period (the 4 weeks prior to the start of treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall record the index of laterality and the percentage of change in the mean count per pixel in each region of interest measured by the brain perfusion tomography, performed on a subsample of the patients within the real and sham acupuncture groups. TRIAL REGISTRATION Current Controlled Trials ISRCTN98703707.

Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

INTRODUCTION Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. METHODS AND ANALYSIS The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. ETHICS AND DISSEMINATION Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. DISCUSSION This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy. TRIAL REGISTRATION NUMBER NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

BACKGROUND Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN A phase II randomized, double-blind pilot clinical trial. SCOPE male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. INSTRUMENTATION clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).

Analysis of genes encoding penicillin-binding proteins in clinical isolates of Acinetobacter baumannii.

There is limited information on the role of penicillin-binding proteins (PBPs) in the resistance of Acinetobacter baumannii to β-lactams. This study presents an analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty-six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from three teaching hospitals in Spain were included. The antimicrobial susceptibility profile, clonal pattern, and genomic species identification were also evaluated. Based on the six complete genomes of A. baumannii, the PBP genes were identified, and primers were designed for each gene. The nucleotide sequences of the genes identified that encode PBPs and the corresponding amino acid sequences were compared with those of ATCC 17978. Seven PBP genes and one monofunctional transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular-mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7 (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot mutation regions were observed, although most of the allelic changes found translated into silent mutations. The amino acid consensus sequences corresponding to the PBP genes in the genomes and the clinical isolates were highly conserved. The changes found in amino acid sequences were associated with concrete clonal patterns but were not directly related to susceptibility or resistance to β-lactams. An insertion sequence disrupting the gene encoding PBP6b was identified in an endemic carbapenem-resistant clone in one of the participant hospitals.

Protocol of the COSMIN study: consensus-based standards for the selection of health measurement instruments

Background: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist.Method: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist.Discussion: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing - a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites.

BACKGROUND: Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five. RESULTS: Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01). CONCLUSION: The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence. CLINICAL TRIAL REGISTRY INFORMATION: Protocol Record Identification Number: 132/03Registry URL: http://www.clinicaltrials.gov.

Impact of a telenursing service on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their families: a crossover randomized trial study protocol.

BACKGROUND: Pediatric rheumatic diseases have a significant impact on children's quality of life and family functioning. Disease control and management of the symptoms are important to minimize disability and pain. Specialist clinical nurses play a key role in supporting medical teams, recognizing poor disease control and the need for treatment changes, providing a resource to patients on treatment options and access to additional support and advice, and identifying best practices to achieve optimal outcomes for patients and their families. This highlights the importance of investigating follow-up telenursing (TN) consultations with experienced, specialist clinical nurses in rheumatology to provide this support to children and their families. METHODS/DESIGN: This randomized crossover, experimental longitudinal study will compare the effects of standard care against a novel telenursing consultation on children's and family outcomes. It will examine children below 16 years old, recently diagnosed with inflammatory rheumatic diseases, who attend the pediatric rheumatology outpatient clinic of a tertiary referral hospital in western Switzerland, and one of their parents. The telenursing consultation, at least once a month, by a qualified, experienced, specialist nurse in pediatric rheumatology will consist of providing affective support, health information, and aid to decision-making. Cox's Interaction Model of Client Health Behavior serves as the theoretical framework for this study. The primary outcome measure is satisfaction and this will be assessed using mixed methods (quantitative and qualitative data). Secondary outcome measures include disease activity, quality of life, adherence to treatment, use of the telenursing service, and cost. We plan to enroll 56 children. DISCUSSION: The telenursing consultation is designed to support parents and children/adolescents during the course of the disease with regular follow-up. This project is novel because it is based on a theoretical standardized intervention, yet it allows for individualized care. We expect this trial to confirm the importance of support by a clinical specialist nurse in improving outcomes for children and adolescents with inflammatory rheumatisms. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Development of a Safety protocol for Management Thirst in the Immediate Postoperative Period

Objective To develop a safety protocol for the management of thirst in the immediate postoperative period. Method Quantitative, methodological, and applied study conducted in April-August 2012. An extensive literature search and expert consultation was carried out to develop the protocol and its operating manual. Theoretical and semantic analyzes were carried out by experts. Results Assessment of level of consciousness, reflexes of protection of the airways (cough and swallowing), and absence of nausea and vomiting were selected as safety criteria. These criteria were grouped and formatted in a graph algorithm, which indicates the need to interrupt the procedure if a security criterion does not reach the expected standard. Conclusion The protocol was elaborated to fill in the gap in the literature of a specific model concerning nursing actions in the safe management of thirst in the immediate postoperative period.

Effective continuing professional development for translating shared decision making in primary care: A study protocol.

Background: Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the healthcare professional and the patient. SDM is the essential element of patient-centered care, a core concept of primary care. However, SDM is seldom translated into primary practice. Continuing professional development (CPD) is the principal means by which healthcare professionals continue to gain, improve, and broaden the knowledge and skills required for patient-centered care. Our international collaboration seeks to improve the knowledge base of CPD that targets translating SDM into the clinical practice of primary care in diverse healthcare systems. Methods: Funded by the Canadian Institutes of Health Research (CIHR), our project is to form an international, interdisciplinary research team composed of health services researchers, physicians, nurses, psychologists, dietitians, CPD decision makers and others who will study how CPD causes SDM to be practiced in primary care. We will perform an environmental scan to create an inventory of CPD programs and related activities for translating SDM into clinical practice. These programs will be critically assessed and compared according to their strengths and limitations. We will use the empirical data that results from the environmental scan and the critical appraisal to identify knowledge gaps and generate a research agenda during a two-day workshop to be held in Quebec City. We will ask CPD stakeholders to validate these knowledge gaps and the research agenda. Discussion: This project will analyse existing CPD programs and related activities for translating SDM into the practice of primary care. Because this international collaboration will develop and identify various factors influencing SDM, the project could shed new light on how SDM is implemented in primary care.

Need of reduced and harmonized bureaucracy in multi-centre clinical research - a case-report from a Swiss trial

Introduction: We launched an investigator-initiated study (ISRCTN31181395) to evaluate the potential benefit of pharmacokinetic-guided dosage individualization of imatinib for leukaemiapatients followed in public and private sectors. Following approval by the research ethics committee (REC) of the coordinating centre, recruitment throughout Switzerland necessitatedto submit the protocol to 11 cantonal RECs.Materials and Methods: We analysed requirements and evaluation procedures of the 12 RECs with associated costs.Results: 1-18 copies of the dossier, in total 4300 printed pages, were required (printing/posting costs: ~300 CHF) to meet initial requirements. Meeting frequencies of RECs ranged between 2 weeks and 2 months, time from submission to fi rst feedback took 2-75 days. Study approval was obtained from a chairman, a subor the full committee, the evaluation work being invoiced by0-1000 CHF (median: 750 CHF, total: 9200 CHF). While 5 RECs gave immediate approval, the other 6 rose in total 38 queries before study release, mainly related to wording in the patient information, leading to 7 different fi nal versions approved. Submission tasks employed an investigator half-time over about 6 months.Conclusion: While the necessity of clinical research evaluation by independent RECs is undisputed, there is a need of further harmonization and cooperation in evaluation procedures. Current administrative burden is indeed complex, time-consuming and costly. A harmonized electronic application form, preferably compatible with other regulatory bodies and European countries, could increase transparency, improve communication, and encourage academic multi-centre clinical research in Switzerland.

Implementation study of a clinical prediction score to rule out cardiogenic chest pain in community: Cluster randomized trial

1.1 Fundamentals Chest pain is a common complaint in primary care patients (1 to 3% of all consultations) (1) and its aetiology can be miscellaneous, from harmless to potentially life threatening conditions. In primary care practice, the most prevalent aetiologies are: chest wall syndrome (43%), coronary heart disease (12%) and anxiety (7%) (2). In up to 20% of cases, potentially serious conditions as cardiac, respiratory or neoplasic diseases underlie chest pain. In this context, a large number of laboratory tests are run (42%) and over 16% of patients are referred to a specialist or hospitalized (2).¦A cardiovascular origin to chest pain can threaten patient's life and investigations run to exclude a serious condition can be expensive and involve a large number of exams or referral to specialist -­‐ often without real clinical need. In emergency settings, up to 80% of chest pains in patients are due to cardiovascular events (3) and scoring methods have been developed to identify conditions such as coronary heart disease (HD) quickly and efficiently (4-­‐6). In primary care, a cardiovascular origin is present in only about 12% of patients with chest pain (2) and general practitioners (GPs) need to exclude as safely as possible a potential serious condition underlying chest pain. A simple clinical prediction rule (CPR) like those available in emergency settings may therefore help GPs and spare time and extra investigations in ruling out CHD in primary care patients. Such a tool may also help GPs reassure patients with more common origin to chest pain.

Treatment options related to clinical type

Treatment of status epilepticus (SE) consists in the sequential administration of three lines of drugs. The first is represented by benzodiazepines, and enjoys quite robust scientific evidence. The second one includes (phos-) phenytoin, valproate, phenobarbital, and increasingly levetiracetam, but its rationale is relatively scarce. The third line is pharmacological coma induction with barbiturates, propofol, or midazolam, which lacks the support of prospective, controlled studies and is reserved for refractory SE. Several other drugs are used after failure of this scheme, including newer antiepileptic compounds, other medications, and non-pharmacological approaches; no comparative assessment of their respective role has been conducted. It is important to tailor this relatively simple protocol to each particular situation; the supposed advantages of coma induction should be balanced with the morbidity related to prolonged mechanical ventilation. Awide consensus exists to treat generalized-convulsive SE and SE in coma soon and aggressively, to prevent a dismal outcome. On the other side, it is unclear if complex-partial SE induces permanent neuronal damage, and absence SE has an excellent prognosis: it appears therefore advisable not to proceed automatically to coma induction in these cases. SE related to post-anoxic coma has generally a poor prognosis, but some selected cases seem to be amenable to a better outcome if treated. SE prognosis depends on etiology, the biological background including age and comorbidities, and, possibly, treatment; each of these points deserves to be specifically addressed. A simple prognostic score has been recently validated and, helping to orient early treatment strategies and improve SE management.

A low-dose stimulation protocol using highly purified follicle-stimulating hormone can lead to high pregnancy rates in in vitro fertilization patients with polycystic ovaries who are at risk of a high ovarian response to gonadotropins.

OBJECTIVE: To study the benefits of a low-dose stimulation (LDS) protocol with purified urinary follicle-stimulating hormone in patients with polycystic ovaries who have presented previously with a very high ovarian response to a standard hMG stimulation. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S): Sixty-one patients involved in an IVF/ICSI program from January 1995 to December 1996. INTERVENTION(S): The patients were first stimulated with a standard protocol using hMG and presented with a very high ovarian response. These patients were then stimulated a second time using a low-dose protocol. Cryopreserved embryos were transferred in later artificial or natural cycles until to December 1999. MAIN OUTCOME MEASURE(S): Number of gonadotropin ampules; estradiol level on the day of ovulation induction; follicles, oocytes, and cryopreserved zygotes; fertilization, implantation, and pregnancy rates; and number of ovarian hyperstimulation syndromes (OHSS). RESULT(S): The number of ampules used, the estradiol level reached, and the number of oocytes obtained were significantly lower under the LDS than the standard protocol. High implantation (21.8%) and clinical pregnancy (38.4%) rates were obtained after LDS. The cumulated deliveries per cycle started and per patient were, respectively, 41.6% and 52.5%. Five patients suffered OHSS with the standard protocol, and none with the LDS. CONCLUSION(S): The LDS protocol offers a safe and efficient treatment for patients who present with echographic polycystic ovaries and are at risk of an excessive ovarian response to standard IVF stimulation protocols.