[Interdisciplinary multimodal assessment and risk-tailored pathways for patients with back pain : Prospective evaluation of an integrated healthcare delivery project]. / Interdisziplinär-multimodales sektorenübergreifendes Assessment und bedarfsorientierte Steuerung für Patienten mit Rückenschmerzen : Prospektive Evaluation eines integrierten Versorgungsprojekts.

BACKGROUND: Back pain is prevalent in the population, sometimes recurrent and may result in everyday and work disabilities. It is often a reason for seeking healthcare support. Analyzing the need of treatment and chronification-risk tailored intervention is a particular demand in healthcare delivery. OBJECTIVES: Reducing downstream consequences of back pain (e. g. pain and disability) by using an interdisciplinary multimodal assessment followed by a risk-tailored intervention. METHODS: Patients with back pain (n = 1638) underwent assessments based on the German Pain Questionnaire (GPQ) and the diagnostic assessment each by a team comprising a physician, a psychologist and a physiotherapist. They were assessed answering a follow-up questionnaire after 6 and/or 12 months (n = 832) for success criteria sensitive to change as pain, everyday and work disability. RESULTS: Patients had on average 62.5 days of work disability and 53.3% had pain up to one year. After assessment, 1447 patients (88.3%) were assigned to receive an intensive interdisciplinary multimodal back pain intervention. Intervention groups were: 120 h of full-time treatment for 4 weeks (n = 1030) or 60 h (n = 224), 48 h part time treatment for 3 months (n = 87), and in-patient hospital treatment for about 17 days (n = 106). The effect sizes of success criteria were large to very large in all treatment groups. CONCLUSIONS: Tailored, interdisciplinary and intensive intervention is effective in reducing downstream consequences of back pain. The treatment assignment was based on patient reports (GPQ score) and multidisciplinary assessments (clinical evidence score). Tailored interventions should include sufficient intensity for highly disabled patients. Care integration such as timely communication between the health insurance system, back pain centers and usual healthcare services as well as patient- and process-related documentation are crucial for this intervention.

[Treatment effects and cost-effectiveness of interdisciplinary multimodal pain treatment of patients with back pain : A controlled observational intervention study based on claims data and survey data of participants]. / Behandlungs- und Kosteneffekte der interdisziplinären multimodalen Schmerztherapie bei Patienten mit Rückenschmerz : Eine kontrollierte, nicht-randomisierte Interventionsstudie mit GKV-Daten und Teilnehmerbefragung.

BACKGROUND: Persons insured by AOK Nordost statutory health insurance (SHI) and on sick leave underwent a 20-day program of interdisciplinary multimodal pain therapy (IMST) following an initial assessment (IA). We evaluated its effectiveness regarding sick leave, utilization/costs of SHI services, and patient-reported characteristics of pain. MATERIALS AND METHODS: Participants with >14 days of IMST in 2013-2015 and with data necessary for comparison (intervention group, IG) were matched 1:1 in 2 steps. From AOK Nordost data, we identified a comparison group (CG) having characteristics matching exactly and by propensity score. Starting on the IA (IG) or a comparable reference day (CG), we analyzed utilization/costs of services related to back pain for 365 days. Participants' characteristics of pain were surveyed on the IA day and within 183-365 days. RESULTS: The 86 IG patients had on average 44.33 (median 12) days of sick leave less than the CG after their initial sick leave starting at the IA (significant, p <0.05). Fewer IG patients had ≥1 hospitalization (OR 0.33; 95%CI 0.12-0.88), ≥1 prescription of physiotherapy (OR 0.35; 95%CI 0.24-0.82), and ≥1 specialist visit (OR 0.39; 95%CI 0.10-0.52) related to back pain. More IG patients had "lasting absence of treatment" (OR 4.06; 95%CI 1.09-15.1). Follow-up interviews were available for 56 IG patients, showing less pain intensity, impairment by pain, and pain severity (significant). Regarding the SHI perspective, cost savings per patient nearly covered the IA and IMST costs. DISCUSSION: For a selected comparable population treated by protocol, IA and IMST was associated with reduction or "lasting absence" of treatment, pain relief, and major savings on sickness benefits. Other than in previous studies we found coverage of IA and IMST costs without consideration of productivity loss.

1,10-Phenanthroline-dithiine iridium and ruthenium complexes: synthesis, characterization and photocatalytic dihydrogen evolution.

We report the synthesis and the spectroscopic and electrochemical properties of six mononuclear iridium(iii) and ruthenium(ii) complexes bearing S,S'-extended phenanthroline ligands. Starting from 5,6-dibromide-1,10-phenanthroline, the dithiine derivatives N,N'-1,10-phenanthrolinedithiino[2,3-b]quinoxaline and N,N'-1,10-phenanthrolinedithiino[2,3-b]benzene were prepared by primary N,N'-complexation of the dibromo derivative and subsequent nucleophilic substitution at the complex. The photoluminescence of the phenanthroline-dithiine containing complexes shows distinctively increased lifetimes for all Ir(iii) and Ru(ii) complexes. The activity of the series of Ir(iii) and Ru(ii) complexes as photosensitizers in visible-light photocatalytic water reduction is demonstrated by dihydrogen evolution with a [Fe3(CO)12] catalyst and triethylamine as a sacrificial donor.

Limits on Momentum-Dependent Asymmetric Dark Matter with CRESST-II.

The usual assumption in direct dark matter searches is to consider only the spin-dependent or spin-independent scattering of dark matter particles. However, especially in models with light dark matter particles O(GeV/c^{2}), operators which carry additional powers of the momentum transfer q^{2} can become dominant. One such model based on asymmetric dark matter has been invoked to overcome discrepancies in helioseismology and an indication was found for a particle with a preferred mass of 3 GeV/c^{2} and a cross section of 10^{-37} cm^{2}. Recent data from the CRESST-II experiment, which uses cryogenic detectors based on CaWO_{4} to search for nuclear recoils induced by dark matter particles, are used to constrain these momentum-dependent models. The low energy threshold of 307 eV for nuclear recoils of the detector used, allows us to rule out the proposed best fit value above.

[Efficacy of epidural steroid injections for chronic lumbar pain syndromes without neurological deficits. A randomized, double blind study as part of a multimodal treatment concept]. / Wirksamkeit periduraler Steroidinjektionen in der Therapie von nichtradikulären chronischen Rückenschmerzen. Eine randomisierte, doppelverblindete Vergleichsstudie im Rahmen eines multimodalen Behandlungskonzeptes.

BACKGROUND: Chronic lumbar pain syndromes without neurological deficits are generated by a multitude of causes. Functional, morphological and psychosocial factors are discussed. In many cases a diseased intervertebral disc is found on radiological examination but the clinical relevance of these findings is not clear. For this study it was postulated that a diseased disc results in a local inflammatory reaction therefore causing pain and impairing treatability of patients. An epidural injection of steroids can reduce inflammation and therefore improve treatability and ultimately treatment outcome. METHODS: A double blind randomized prospective trial was carried out. Patients treated in hospital for a chronic lumbar pain syndrome without neurological deficits within a multimodal treatment program were screened for indications for an epidural steroid injection (e.g. diseased lumbar disc and intention to treat). Patients eligible for the study were randomized into two groups. The treatment group received an epidural injection of 80 mg triamcinolone and 8 ml bupivacaine 0.25 %. The control group received only an epidural injection of 8 ml bupivacaine 0.25 %. RESULTS: In both groups pain intensity and treatability showed a statistically significant improvement after the epidural injection. The differences between the control and treatment groups were small and not clinically relevant. A small subgroup might profit from the steroid injection. In addition the treatability was dependent on psychometric values and the long-term outcome from a reduction of muscular skeletal dysfunctions. DISCUSSION: After the epidural injection the decrease in pain and increase in treatability was statistically significant. The mechanism of the improvement is not clear and should be examined further. The epidural injection of a steroid in this subgroup of patients did not lead to a clinical improvement in the outcome.

Optical excitation of Josephson plasma solitons in a cuprate superconductor.

Josephson plasma waves are linear electromagnetic modes that propagate along the planes of cuprate superconductors, sustained by interlayer tunnelling supercurrents. For strong electromagnetic fields, as the supercurrents approach the critical value, the electrodynamics become highly nonlinear. Josephson plasma solitons (JPSs) are breather excitations predicted in this regime, bound vortex-antivortex pairs that propagate coherently without dispersion. We experimentally demonstrate the excitation of a JPS in La1.84Sr0.16CuO4, using intense narrowband radiation from an infrared free-electron laser tuned to the 2-THz Josephson plasma resonance. The JPS becomes observable as it causes a transparency window in the opaque spectral region immediately below the plasma resonance. Optical control of magnetic-flux-carrying solitons may lead to new applications in terahertz-frequency plasmonics, in information storage and transport and in the manipulation of high-Tc superconductivity.

[The anti-Jo-1 syndrome - a specific form of myositis with interstitial lung disease]. / Das Anti-Jo-1-Syndrom - eine Sonderform der Myositis mit interstitieller Lungenerkrankung.

Interstitial lung disease (ILD) may be associated with systemic inflammatory disorders and autoantibody production. The development of ILD has been described in detail in patients with polymyositis and dermatomyositis. Anti-synthetase antibodies, including anti-Jo-1 antibodies (antihistidyl-tRNA syntase), are found in up to 35 % of patients with myositis, 80 % of which constitute anti-Jo-1 antibodies. The anti-Jo-1 syndrome characteristically presents with myositis, shortness of breath, fever, polyarthritis/arthralgia, mechanic's hands, dermatomyositis-like skin lesions, signs of a connective tissue disease and/or Raynaud's phenomenon. ILD is an early diagnostic sign and shows focal infiltrates and an acinar pattern in CT scan. Non-specific interstitial pneumonitis with T-lymphocytic infiltrates in lung histology (VATS) or elevated IFN-gamma-inducible chemokines are further indicators for anti-Jo-1 syndrome. Corticosteroids eventually combined with an immunosuppressant drug are often required with reported beneficial effects, although not many therapeutic studies have been performed. Here we present a review of the current literature and a case report on anti-Jo-1 syndrome.

Treatment of a 12-hour shift of sleep schedule with benzodiazepines.

Normal sleepers underwent sleep recordings and daytime tests of sleep tendency, performance, and mood while being shifted 180 degrees in their sleep-wake schedule. After two baseline 24-hour periods, subjects postponed sleep until noon. For the next three 24-hour periods, they were in bed from 1200 to 2000 and received triazolam, flurazepam, or placebo at bedtime in parallel groups. Placebo subjects showed significant sleep loss after the shift. Active medication reversed this sleep loss. Despite good sleep, flurazepam subjects appeared most impaired of the three groups on objective assessments of waking function; triazolam subjects were least impaired.

[Functional diagnostics of mobility control, mobility stabilization and hypermobility. Reliability of clinical tests - results of a multicenter study]. / Funktionelle Diagnostik der Bewegungssteuerung, Bewegungsstabilisation und Hypermobilität. Reliabilität klinischer Tests - Ergebnisse einer Multicenterstudie.

BACKGROUND: Complex forms of musculoskeletal dysfunction are thought to be risk factors for the development of chronic pain syndromes of the locomotor system. Unfortunately there are insufficient data on the reliability and validity of clinical tests for musculoskeletal dysfunctions. METHOD: The intrarater and interrater reliability of clinical tests for hypermobility and for the stabilisation system were examined in a multicentre trial. A total of 68 patients in 6 centres were functionally examined by 2 examiners once (intrarater reliability) and by 1 examiner twice (interrater reliability). RESULTS: The tests for hypermobility showed good to very good reliability. The results for the stabilisation system were more variable whereby 23 tests showed a kappa-coefficient greater than 0.5 and 15 tests good to very good reliability. DISCUSSION: All tests for hypermobility and 23 tests for the stabilisation system are suitable for further evaluation. The broad range in test reliability might be explained by the differences in examiner skills demanded by each test. Therefore, dependent on their validity, some tests will be useful in specialized centres while others might be used in primary care.

[A 29-year-old man with Takayasu's arteritis]. / Ein 29-jähriger Patient mit dem Bild einer Takayasu-Arteriitis.

We report on a 29-year-old male patient with collapse and recurrent vertigo. Physical examination showed a bruit of the left common carotid artery on auscultation and a pulselessness of both arms. The diagnosis of Takayasu's arteritis was based on the results of duplex sonography, MRI and angiography (stenosis and occlusion of extracranial arteries). Laboratory results did not reveal any specific changes. Combined treatment with prednisolone and azathioprine was initiated. After 12 days we saw an improvement of duplexsonographical and laboratory findings. Takayasu's disease should be considered as a differential diagnosis in patients with stenosis and occlusions of the aortic arch and its main branches (e.g. pulselessness). MRI is a valuable method in detection of wall abnormalities of the aorta, its branches and other large arteries.

High-Field High-Repetition-Rate Sources for the Coherent THz Control of Matter.

Ultrashort flashes of THz light with low photon energies of a few meV, but strong electric or magnetic field transients have recently been employed to prepare various fascinating nonequilibrium states in matter. Here we present a new class of sources based on superradiant enhancement of radiation from relativistic electron bunches in a compact electron accelerator that we believe will revolutionize experiments in this field. Our prototype source generates high-field THz pulses at unprecedented quasi-continuous-wave repetition rates up to the MHz regime. We demonstrate parameters that exceed state-of-the-art laser-based sources by more than 2 orders of magnitude. The peak fields and the repetition rates are highly scalable and once fully operational this type of sources will routinely provide 1 MV/cm electric fields and 0.3 T magnetic fields at repetition rates of few 100 kHz. We benchmark the unique properties by performing a resonant coherent THz control experiment with few 10 fs resolution.

Immunochemical detection of N2-[1-(1-carboxy)ethyl]guanosine, an advanced glycation end product formed by the reaction of DNA and reducing sugars or L-ascorbic acid in vitro.

In the Maillard reaction, free amino groups of proteins and nucleic acids react with reducing sugars to form advanced glycation end products (AGE). A major product found in reaction mixtures of guanosine and glucose is N2-[1-(1-carboxy)ethyl]guanosine (CEG), which, therefore, can be used as a marker of advanced glycation of DNA. An enzyme-linked immunosorbent assay (ELISA) was developed to detect and to semi-quantitate nonenzymatic glycosylation of DNA. A polyclonal antiserum was raised against CEG linked to keyhole limpet hemocyanin. A protocol for a competitive ELISA was developed, and the antiserum was tested for crossreactivity. Several unmodified nucleotides and N2-modified guanosine derivatives showed no or negligible crossreactivity. Only very similar structures like N2-(carboxymethyl)guanosine and N2-(1-carboxy-3-hydroxypropyl)guanosine, which have been identified as reaction products of glucose or l-ascorbic acid and guanosine, display significant binding activity. The signal can be totally repressed by free CEG, yet protein-bound CEG is a stronger inhibitor. DNA incubated with d-glucose, dihydroxyacetone, l-ascorbic or l-dehydroascorbic acid shows a signal inhibition indicating the formation of CEG in vitro. The competitive ELISA procedure proved to be a sensitive method which can be used to detect glycation of DNA in vivo.

Single-pulse picking at kHz repetition rates using a Ge plasma switch at the free-electron laser FELBE.

We demonstrate a system for picking of mid-infrared and terahertz (THz) radiation pulses from the free-electron laser (FEL) FELBE operating at a repetition rate of 13 MHz. Single pulses are reflected by a dense electron-hole plasma in a Ge slab that is photoexcited by amplified near-infrared (NIR) laser systems operating at repetition rates of 1 kHz and 100 kHz, respectively. The peak intensity of picked pulses is up to 400 times larger than the peak intensity of residual pulses. The required NIR fluence for picking pulses at wavelengths in the range from 5 µm to 30 µm is discussed. In addition, we show that the reflectivity of the plasma decays on a time scale from 100 ps to 1 ns dependent on the wavelengths of the FEL and the NIR laser. The plasma switch enables experiments with the FEL that require high peak power but lower average power. Furthermore, the system is well suited to investigate processes with decay times in the µs to ms regime, i.e., much longer than the 77 ns long pulse repetition period of FELBE.

MSLT-defined sleepiness and neuropsychological test performance do not correlate in the elderly.

This study investigated whether a sensitive, physiological measure of alertness/sleepiness, the Multiple Sleep Latency Test (MSLT), was related to neuropsychological test performance in elderly individuals. We hypothesized that the greater likelihood of falling asleep during the daytime on the MSLT would be related to relatively poorer performances on a variety of neuropsychological tests. Results from a homogeneous sample of 35 relatively well-educated, high functioning, elderly community volunteers confirmed the presence of characteristic levels of daytime alertness which were stable within individuals (r = .70 to .73) and showed large variation across individuals (coefficients of variation: 54-84%). Despite this wide intersubject variability, MSLT-defined alertness/sleepiness was unrelated to neuropsychological test results. We discuss these results in terms of the performance deficits known to accompany sleepiness in experimental studies of sleep deprivation and in terms of the behavioral slowing known to occur in normal aging.

Dose-related effects of triazolam and flurazepam on a circadian rhythm insomnia.

Forty-eight normal subjects had sleep recordings and multiple sleep latency tests (an EEG measure of sleepiness) before and after a 12-hour shift of sleep-wake schedule. After 2 baseline days, subjects postponed sleep until 12:00 noon, then for three 24-hour periods were in bed from 12:00 noon until 8:00 PM. Treatment in parallel groups were administered before shifted sleeps. Sleep disturbance was greatest in the last quarter of shifted nights (6.5 to 8.5 hours after medication). Subjects taking placebo showed significant sleep loss on shifted nights and increased sleepiness the next day. Triazolam, 0.5 mg, reversed the sleep loss and consequent daytime sleepiness associated with the shifted sleep schedule. Triazolam, 0.25 mg, was not significantly better than placebo. In a dose-related manner, flurazepam mitigated the insomnia, but carryover effects left both dose groups more sleepy than were the placebo control subjects. Whether these laboratory results are applicable to clinically occurring forms of transient insomnia remains to be seen.

Nighttime and daytime efficacy of flurazepam and oxazepam in chronic insomnia.

Trials of hypnotic medications typically determine efficacy by examining changes in polysomnographically recorded sleep and in daytime performance. The authors employed daytime sleepiness as a new, potentially crucial criterion in such trials. Oxazepam and flurazepam were effective in improving some polysomnographically defined measures of nocturnal sleep in 14 patients with chronic insomnia; flurazepam produced substantial daytime sleepiness and oxazepam did not. Oxazepam produced some rebound insomnia, consisting of about an hour's reduction of polysomnographically defined sleep, but without gross mood disturbance or the patients' awareness of sleep loss.

Mapping of linear epitopes on fibre knob of human adenovirus serotype 5.

Linear antigenic epitopes on the Ad5 fibre knob (FK5) were characterised with fibre- and virion-specific antisera, using 15-mer overlapping peptides covering the knob of the fibre. They were compared with epitopes on the Ad2 fibre knob (FK2) domain. The stronger reactive FK5 epitopes were represented by peptides P3 (amino acids (aa A419-L433)), P6 (aa S449-E463), P7 (aa I459-L473), P12 (aa G509-N523), P14 (aa P529-G543) and P16 (aa A549-Y563). P3 spans the B beta-strand and the left portion of the C beta-strand, P6 and P7 the D beta-strand and the adjacent parts of the CD and DE loops, P12, P14 and P16 the G, H and I beta strands and the adjacent parts of the loops, respectively. The stronger reactive epitopes on FK2 were located in P2 (aa P409-L423), P6 (aa T449-Q463), P8 (aa E469-G483), P13 (aa Q519-T533) and P16 (aa S549-K563). The positions of FK5 and FK2 derived peptides, representing epitopes, are either identical or overlapping or adjacent, as determined by amino acid sequence alignment. Antisera obtained against several longer peptides showed virus neutralising capacity, indicating neutralising epitopes in these peptides.

Inhibition of cell adhesion to the virus by synthetic peptides of fiber knob of human adenovirus serotypes 2 and 3 and virus neutralisation by anti-peptide antibodies.

The fiber knob of adenovirus (Ad) causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s) several synthetic peptides derived from Ad2 and Ad3 fiber head sequences and their antisera were tested for interference with virus attachment to HeLa and FL cells and cell adhesion to viruses. The anti-peptide sera were also evaluated in ELISA and virus neutralisation test. Ad2 (of subgroup C) and Ad3 (of subgroup B) attachment was not significantly inhibited by peptides corresponding to the amino acid residues 535-554, 555-573, 562-582 of Ad2 fiber or 210-225, 267-283, 291-306 and 300-319 of Ad3 fiber. However, microplate pre-adsorbed Ad3 fiber residues 210-225 and 267-283 could bind FL and HeLa cells, and 1 mg/ml of Ad3 fiber residues 267-283 inhibited the cell adhesion to Ad3 virus to approximately 90%. This peptide may participate in the receptor binding site of Ad3 fiber. ELISA reactive anti-peptide antibodies against the homologous peptide and virus did not significantly reduce the cell adhesion to the immobilised virus or the virus attachment to cells, but in the neutralisation assay antibodies raised to Ad2 fiber residues 555-573 and 562-582 and Ad3 fiber residues 210-225 caused neutralisation of the homologous virus at serum dilutions of 1:500 and 1:32, respectively. The corresponding peptides and one further peptide of Ad2 fiber and two of Ad3 fiber seem to contain neutralisation epitopes.

Daytime sleepiness as a criterion in hypnotic medication trials: comparison of triazolam and flurazepam.

Sleep laboratory hypnotic medication trials typically determine efficacy by examining changes in polysomnographically recorded sleep. We introduce the use of daytime sleepiness, as assessed by the Multiple Sleep Latency Test (MSLT), as a criterion for daytime functioning in such trials. Two benzodiazepine hypnotics, triazolam (0.5 mg) and flurazepam (30 mg), with short and long half-lives respectively, were compared in a multicentered, double-blind crossover study. Results indicated these medications had virtually indistinguishable nocturnal effects, but differed dramatically during the day. Flurazepam decreased sleep latency on the MSLT, whereas triazolam did not. These results could indicate that daytime sleepiness is a concomitant effect of flurazepam.