The association between beliefs about low back pain and work presenteeism

OBJECTIVE: To examine the influence of beliefs about low back pain (LBP) on reduced productivity at work ("presenteeism") caused by LBP. METHODS: Two thousand five hundred seven individuals completed the Back Beliefs Questionnaire, the Fear Avoidance Beliefs questionnaire (FABQ), and questions about LBP-related work-absence, reduced work-productivity, pain, comorbidity, and demographics. RESULTS: Six hundred seventy (25%) individuals were of working age, employed and reported current LBP. Univariate models showed beliefs were more "negative" in individuals with work-absence and reduced productivity (P = 0.0001). In multivariable analysis, controlling for confounders, "FABQwork" was a unique predictor of both absenteeism and presenteeism (each, P = 0.0001), though with small effect sizes. CONCLUSIONS: Negative beliefs about LBP are associated with both work absence and reduced work-productivity. Further investigations should examine their potential as a target for educational interventions when considering initiatives to reduce the socioeconomic costs of LBP.

Intravaginal and intracervical application of seminal plasma in in vitro fertilization or intracytoplasmic sperm injection treatment cycles--a double-blind, placebo-controlled, randomized pilot study

OBJECTIVE: To evaluate whether intravaginal application of seminal plasma at the time of follicle aspiration in IVF or intracytoplasmic sperm injection treatment cycles has the potential to increase pregnancy rate. To calculate the number of patients needed to achieve significance in a multicenter trial. DESIGN: Double-blind, placebo-controlled randomized pilot study. SETTING: University department of gynecological endocrinology and reproductive medicine. PATIENT(S): One hundred sixty-eight patients undergoing IVF or intracytoplasmic sperm injection treatment. INTERVENTION(S): Cryopreserved seminal plasma from the patient's partner or sodium chloride (placebo) was injected into the cervix and the posterior fornix of the vagina just after follicle aspiration. MAIN OUTCOME MEASURE(S): Clinical-pregnancy rate. RESULT(S): One hundred sixty-eight patients agreed to participate in the study. Participation was limited to one treatment cycle. Thirty-one patients (18%) were excluded from the study, mainly as a result of canceled embryo transfers. Seventy patients received placebo, and 67 received seminal plasma. The clinical-pregnancy rate was 25.7% (18/70) in the placebo group. The clinical-pregnancy rate in the seminal plasma group reached 37.3% (25/67), corresponding to a relative increase of 45%. CONCLUSION(S): Even though significance was not reached in this pilot study, the data suggest that seminal plasma has the potential to improve pregnancy rate. It is estimated that around 450 patients need to be recruited to reach significance in a multicenter study.

Does homeopathically potentized antimony stimulate coagulation? A summary of previous findings and results of an in vitro pilot study by means of thrombelastography

BACKGROUND: Potentized antimony is traditionally used in anthroposophic medicine to enhance hemostasis in bleeding disorders, but evidence of its effectiveness is scarce. On the other hand, non-toxic and economic additional therapeutic options for hemostatic disorders are desirable. OBJECTIVES: We examined all available literature on the subject and performed a controlled pilot in vitro study to test the procoagulatory potency of antimony D 5. DESIGN: Freshly drawn citrated whole blood of 12 healthy volunteers and 12 patients with bleeding disorders was equally distributed into 344 portions, after which it was mixed with antimony D 5, or its potentized vehicle (lactose D 5) as control solution and tested with thrombelastography. The paired t-test and the Wilcoxon signed rank test were used for statistical analysis. In 5 of the 12 healthy donors, a second blood sample was drawn to assess individual variability and increase the total number of replicates. Thus three separate calculations were performed: for the 12 patients, the 12 healthy donors, and the 5 later samples from the same donors. The analysis was exploratory, and no Bonferroni correction was applied. RESULTS: In the antimony D5 samples of the 12 healthy subjects, but not the patients, there was a tendency toward a shorter clotting time (CT) (p = 0.074) and a trend for an increased clot firmness, expressed as maximal amplitude (MA) (p = 0.058). The increase of MA was significant (p = 0.011) when the later samples were included. No statistical difference was detected for the clot formation time and the clot lysis index. CONCLUSION: The exploratory results of this pilot study are inconclusive as to whether antimony D5 has a procoagulatory effect in vitro, although the results suggest an effect on MA and possibly CT. More research is warranted.

Mutation screening of the medium-chain acyl-CoA dehydrogenase (MCAD) and the ornithine transcarbamylase (OTC) genes by multiplex PCR amplification and sequencing

BACKGROUND: Sequencing based mutation screening assays of genes encompassing large numbers of exons could be substantially optimized by multiplex PCR, which enables simultaneous amplification of many targets in one reaction. In the present study, a multiplex PCR protocol originally developed for fragment analysis was evaluated for sequencing based mutation screening of the ornithine transcarbamylase (OTC) and the medium-chain acyl-CoA dehydrogenase (MCAD) genes. METHODS: Single exon and multiplex PCR protocols were applied to generate PCR templates for subsequent DNA sequencing of all exons of the OTC and the MCAD genes. For each PCR protocol and using the same DNA samples, 66 OTC and 98 MCAD sequence reads were generated. The sequences derived from the two different PCR methods were compared at the level of individual signal-to-noise ratios of the four bases and the proportion of high-quality base-signals. RESULTS: The single exon and the multiplex PCR protocol gave qualitatively comparable results for the two genes. CONCLUSIONS: Many existing sequencing based mutation analysis protocols may be easily optimized with the proposed method, since the multiplex PCR protocol was successfully applied without any re-design of the PCR primers and other optimization steps for generating sequencing templates for the OTC and MCAD genes, respectively.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis

OBJECTIVES To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). METHODS Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. RESULTS 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. CONCLUSIONS Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.

Comparative evaluation of the My5-FU™ immunoassay and LC-MS/MS in monitoring the 5-fluorouracil plasma levels in cancer patients

BACKGROUND: Chemotherapies of solid tumors commonly include 5-fluorouracil (5-FU). With standard doses of 5-FU, substantial inter-patient variability has been observed in exposure levels and treatment response. Recently, improved outcomes in colorectal cancer patients due to pharmacokinetically guided 5-FU dosing were reported. We aimed at establishing a rapid and sensitive method for monitoring 5-FU plasma levels in cancer patients in our routine clinical practice. METHODS: Performance of the Saladax My5-FU™ immunoassay was evaluated on the Roche Cobas® Integra 800 analyzer. Subsequently, 5-FU concentrations of 247 clinical plasma samples obtained with this assay were compared to the results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and other commonly used clinical analyzers (Olympus AU400, Roche Cobas c6000, and Thermo Fisher CDx90). RESULTS: The My-FU assay was successfully validated on the Cobas Integra 800 analyzer in terms of linearity, precision, accuracy, recovery, interference, sample carryover, and dilution integrity. Method comparison between the Cobas Integra 800 and LC-MS/MS revealed a proportional bias of 7% towards higher values measured with the My5-FU assay. However, when the Cobas Integra 800 was compared to three other clinical analyzers in addition to LC-MS/MS including 50 samples representing the typical clinical range of 5-FU plasma concentrations, only a small proportional bias (≤1.6%) and a constant bias below the limit of detection was observed. CONCLUSIONS: The My5-FU assay demonstrated robust and highly comparable performance on different analyzers. Therefore, the assay is suitable for monitoring 5-FU plasma levels in routine clinical practice and may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies.

State of Emergency Medicine in Switzerland: a national profile of emergency departments in 2006

BACKGROUND Emergency departments (EDs) are an essential component of any developed health care system. There is, however, no national description of EDs in Switzerland. Our objective was to establish the number and location of EDs, patient visits and flow, medical staff and organization, and capabilities in 2006, as a benchmark before emergency medicine became a subspecialty in Switzerland. METHODS In 2007, we started to create an inventory of all hospital-based EDs with a preliminary list from the Swiss Society of Emergency and Rescue Medicine that was improved with input from ED physicians nationwide. EDs were eligible if they offered acute care 24 h per day, 7 days per week. Our goal was to have 2006 data from at least 80% of all EDs. The survey was initiated in 2007 and the 80% threshold reached in 2012. RESULTS In 2006, Switzerland had a total of 138 hospital-based EDs. The number of ED visits was 1.475 million visits or 20 visits per 100 inhabitants. The median number of visits was 8,806 per year; 25% of EDs admitted 5,000 patients or less, 31% 5,001-10,000 patients, 26% 10,001-20,000 patients, and 17% >20,000 patients per year. Crowding was reported by 84% of EDs with >20,000 visits/year. Residents with limited experience provided care for 77% of visits. Imaging was not immediately available for all patients: standard X-ray within 15 min (70%), non-contrast head CT scan within 15 min (38%), and focused sonography for trauma (70%); 67% of EDs had an intensive care unit within the hospital, and 87% had an operating room always available. CONCLUSIONS Swiss EDs were significant providers of health care in 2006. Crowding, physicians with limited experience, and the heterogeneity of emergency care capabilities were likely threats to the ubiquitous and consistent delivery of quality emergency care, particularly for time-sensitive conditions. Our survey establishes a benchmark to better understand future improvements in Swiss emergency care.

Effects of Lipophilic Extract of Viscum album L. and Oleanolic Acid on Migratory Activity of NIH/3T3 Fibroblasts and on HaCat Keratinocytes

Viscum album L. lipophilic extract (VALE) contains pharmacologically active pentacyclic triterpenes that are known to exhibit immunomodulatory, antitumor, and wound healing activity. Preliminary clinical observations indicate that VALE was able to influence cutaneous wound healing in vivo. The objective of this study was to investigate wound closure related properties of VALE in vitro. As measured in a wound healing assay, VALE and its predominant triterpene oleanolic acid (OA) significantly and dose dependently promoted the migration of NIH/3T3 fibroblasts in vitro, thereby leading to an enhanced wound closure. Compared to the negative control, maximal stimulation by 26.1% and 26.2%, respectively, was attained with 10 μg/mL VALE and 1 μg/mL OA. Stimulation of proliferation in NIH/3T3 fibroblasts by VALE and OA could be excluded. At higher concentrations both substances affected proliferation and viability of NIH/3T3 fibroblasts and HaCat keratinocytes. In the toxic range of concentrations of VALE and OA, migration of NIH/3T3 fibroblasts was suppressed. The extent of the stimulatory effect on cell migration of VALE quite closely corresponded to the effect expected by the concentrations of OA contained in the crude extract VALE. These data support the casual observation that Viscum album L. lipophilic extract might modulate wound healing related processes in vivo.

The influence of inner and heard speech in arts speech therapy on brain oxygenation and hemodynamics

Purpose: Artistic speech therapy is applied in anthroposophically extended medicine to treat several diseases. The aim is to understand the physiology by investigating the effect of inner and heard speech on brain hemodynamics and oxygenation and analyzing whether these changes were affected by changes in arterial carbon dioxide pressure. Methods: In 29 healthy adult volunteers changes in cerebral absolute oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO2) were measured by functional near-infrared spectroscopy (fNIRS). End-tidal CO2 (PETCO2) was assessed by capnography. Each subject performed six tasks: inner speech, heard speech from a person and heard speech from a record with each two different recitation texts: hexameter and alliteration according to a randomized crossover design. Results: Significant changes during tasks: A decrease in StO2, [O2Hb], [tHb] and PETCO2 (only for inner speech); an increase in [HHb]. There was a significant difference between hexameter and alliteration. Particularly, changes in [tHb] at the left prefrontal cortex during tasks and after them were statistically different. Furthermore we found significant relations between changes in [O2Hb], [HHb], [tHb] or StO2 and the participants’ age, the baseline PETCO2, or certain speech tasks. Conclusion: During the inner speech, hyperventilation led to a lower PETCO2 (hypocapnia). During heard speech no significant changes in PETCO2 occurred. But decreases in StO2, [O2Hb], [tHb] suggest hypocapnia also here. Hexameter and alliteration led to different changes in [tHb]. Consequently, our parameters are affected by an interplay of both PETCO2 response and task dependent functional brain activity.

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

The Alexander Technique and musicians: a systematic review of controlled trials

BACKGROUND: Musculoskeletal disorders, stress and performance anxiety are common in musicians. Therefore, some use the Alexander Technique (AT), a psycho-physical method that helps to release unnecessary muscle tension and re-educates non-beneficial movement patterns through intentional inhibition of unwanted habitual behaviours. According to a recent review AT sessions may be effective for chronic back pain. This review aimed to evaluate the evidence for the effectiveness of AT sessions on musicians' performance, anxiety, respiratory function and posture. METHODS: The following electronic databases were searched up to February 2014 for relevant publications: PUBMED, Google Scholar, CINAHL, EMBASE, AMED, PsycINFO and RILM. The search criteria were "Alexander Technique" AND "music*". References were searched, and experts and societies of AT or musicians' medicine contacted for further publications. RESULTS: 237 citations were assessed. 12 studies were included for further analysis, 5 of which were randomised controlled trials (RCTs), 5 controlled but not randomised (CTs), and 2 mixed methods studies. Main outcome measures in RCTs and CTs were music performance, respiratory function, performance anxiety, body use and posture. Music performance was judged by external experts and found to be improved by AT in 1 of 3 RCTs; in 1 RCT comparing neurofeedback (NF) to AT, only NF caused improvements. Respiratory function was investigated in 2 RCTs, but not improved by AT training. Performance anxiety was mostly assessed by questionnaires and decreased by AT in 2 of 2 RCTs and in 2 of 2 CTs. CONCLUSIONS: A variety of outcome measures have been used to investigate the effectiveness of AT sessions in musicians. Evidence from RCTs and CTs suggests that AT sessions may improve performance anxiety in musicians. Effects on music performance, respiratory function and posture yet remain inconclusive. Future trials with well-established study designs are warranted to further and more reliably explore the potential of AT in the interest of musicians.

Reactivity to Accelerometer Measurement of Children and Adolescents

PURPOSE: Awareness of being monitored can influence participants' habitual physical activity (PA) behavior. This reactivity effect may threaten the validity of PA assessment. Reports on reactivity when measuring the PA of children and adolescents have been inconsistent. The aim of this study was to investigate whether PA outcomes measured by accelerometer devices differ from measurement day to measurement day and whether the day of the week and the day on which measurement started influence these differences. METHODS: Accelerometer data (counts per minute [cpm]) of children and adolescents (n = 2081) pooled from eight studies in Switzerland with at least 10 h of daily valid recording were investigated for effects of measurement day, day of the week, and start day using mixed linear regression. RESULTS: The first measurement day was the most active day. Counts per minute were significantly higher than on the second to the sixth day, but not on the seventh day. Differences in the age-adjusted means between the first and consecutive days ranged from 23 to 45 cpm (3.6%-7.1%). In preschoolchildren, the differences almost reached 10%. The start day significantly influenced PA outcome measures. CONCLUSIONS: Reactivity to accelerometer measurement of PA is likely to be present to an extent of approximately 5% on the first day and may introduce a relevant bias to accelerometer-based studies. In preschoolchildren, the effects are larger than those in elementary and secondary schoolchildren. As the day of the week and the start day significantly influence PA estimates, researchers should plan for at least one familiarization day in school-age children and randomly assign start days.

Disease-modifying genes and monogenic disorders: experience in cystic fibrosis

The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders. Significant advances in genetic technologies and molecular medicine allow huge amounts of information to be generated from individual samples within a reasonable time frame. This review focuses on the role of modifier genes using the example of cystic fibrosis, the most common lethal autosomal recessive disorder in the white population, and discusses the advantages and limitations of candidate gene approaches versus genome-wide association studies. Moreover, the implications of modifier gene research for other monogenic disorders, as well as its significance for diagnostic, prognostic, and therapeutic approaches are summarized. Increasing insight into modifying mechanisms opens up new perspectives, dispelling the idea of genetic disorders being caused by one single gene.