Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

[Drug Output and Aerosol Characteristics of Different Jet Nebulisers for Adults While Simulating the Nebulisation of Salbutamol]. / Aerosolcharakteristika ausgewählter Druckluftvernebler für Erwachsene in Simulationsmodellen und Verneblung von Salbutamol.

AIM: Successful inhalation therapy with nebulisers depends on the amount and quality of the aerosol. Choosing a nebuliser requires knowledge of relevant aerosol characteristics. METHODS: We analysed the aerosol performance of 9 commercially available jet nebulisers in 2 in vitro simulation models by assessing the aerosol delivery of albuterol (Sultanol forte® Inhalation Solution 2.5 mg/2.5 ml; GSK) over 4 minutes. The output parameters were analysed with PARI Compas II breath simulator mimicking an adult breathing pattern (Ph.Eur.9.0; n = 5/6 nebulisation), and the aerodynamic particle size distribution was determined by the Next Generation Impactor (Ph.Eur.9.0, Copley Scientific; n = 3 nebulisation). RESULTS: The aerosol performance of the devices differed considerably. The DDR varied from 196 µg/min (PARI LC Sprint (blue)) to 67 µg/min (MIDINEB). The Respirable Drug Delivery Rate (RDDR), calculated from the DDR and the Fine Particle Fraction ≤ 5 µm, varied by a factor of 3.5 between the nebulisers tested. CONCLUSION: The results of the in vitro simulation studies can be utilised to select an appropriate nebuliser for the individual patient. In order to enhance therapeutic efficacy and patient compliance, a nebuliser with a high RDDR should be selected.

Prospective, systematically recorded mycophenolate safety data in Graves' orbitopathy.

CONTEXT: The antiproliferative mechanism of mycophenolate acid (MPA) suggests a beneficial effect in patients with Graves' orbitopathy (GO). OBJECTIVE: To systematically analyze for the first time adverse events (AEs) during MPA treatment in GO. DESIGN: Prospective longitudinal study. SETTING: Academic tertiary referral center with a joint thyroid-eye clinic. PATIENTS: Fifty-three consecutive, unselected patients with clinically active and moderate-to-severe GO. METHODS: MPA 0.720 g was given once daily for 24-weeks in GO patients. AEs were documented and coded according to the standardized medical dictionary for regulatory activities (MedDRA). AE were followed up and seriousness as defined by ICH-guideline E6 was documented. All AEs were analyzed regarding a possible underlying cause and if not, graded as side effect (SE). RESULTS: Fifty GO patients (93 %) had Graves' disease, 37 (70 %) and 29 (54.7 %) were female and smoker, respectively. Thirty-six patients (68 %) reported at least one AE. A total of 88 AEs were documented, most frequent AEs were insomnia (N = 6), fatigue (N = 5) and optic neuropathy (N = 5), while other AEs occurred in up to three patients (5.6 %), only. In 12 (23 %) patients, at least one SE occurred. All 17 reported SE, i.e. mild infections and gastrointestinal intolerance were within the known safety profile of MPA. No patient dropped MPA medication because of drug-induced SE. Most AEs showed a recovered (76 %) or recovering (16 %) outcome. Seven (13 %) patients were hospitalized, five (62 %) due to optic neuropathy, none of these events was graded as SE. CONCLUSIONS: MedDRA-coded data documented the good tolerance of a moderate MPA dose in GO patients.

Non-invasive imaging demonstrates clinical features of ankylosing spondylitis in a rat adjuvant model: a case study.

Ankylosing spondylitis is a common rheumatic disease involving both inflammatory erosive osteopenia and bony overgrowth. Main disease features are recapitulated in small rodents challenged with complete Freund's adjuvant. MRI was used to follow longitudinally in vivo changes induced in the rat spine and micro-CT as terminal assessment of bone damage. Histochemistry methods were used to validate these imaging modalities in view of preclinical drug testing and translational applications of spine imaging. Animals were examined using a 3D fat-suppressed gradient-echo sequence, following the injection of gadolinium. At the end of the study, spines were excised for micro-CT and histological examination. Signals reflecting inflammation were detected at levels L5-L6 of the lumbar spine throughout the experimental period, peaking at day 27 after adjuvant. At day 14 the inflammatory response occurred along ligaments but it expanded to nearby soft tissues at later time points. From day 27 onwards inflammation was also detected within the bone, in areas where erosion occurred, and bone-like structures were formed. Micro-CT showed bone remodeling. Histology of isolated spines confirmed the inflammation and bone remodeling observed in vivo. The present study including three complementary approaches clearly demonstrates the potential of imaging for longitudinal assessments of changes in the spine in this animal model in view of preclinical pharmacological studies. The excellent correlation seen between the in vivo images and the histology underlines its fundamental role in the validation of non-invasive imaging readouts.

Effects of momentary self-monitoring on empowerment in a randomized controlled trial in patients with depression.

BACKGROUND: Interventions based on the experience sampling method (ESM) are ideally suited to provide insight into personal, contextualized affective patterns in the flow of daily life. Recently, we showed that an ESM-intervention focusing on positive affect was associated with a decrease in symptoms in patients with depression. The aim of the present study was to examine whether ESM-intervention increased patient empowerment. METHODS: Depressed out-patients (n=102) receiving psychopharmacological treatment who had participated in a randomized controlled trial with three arms: (i) an experimental group receiving six weeks of ESM self-monitoring combined with weekly feedback sessions, (ii) a pseudo-experimental group participating in six weeks of ESM self-monitoring without feedback, and (iii) a control group (treatment as usual only). Patients were recruited in the Netherlands between January 2010 and February 2012. Self-report empowerment scores were obtained pre- and post-intervention. RESULTS: There was an effect of group×assessment period, indicating that the experimental (B=7.26, P=0.061, d=0.44, statistically imprecise) and pseudo-experimental group (B=11.19, P=0.003, d=0.76) increased more in reported empowerment compared to the control group. In the pseudo-experimental group, 29% of the participants showed a statistically reliable increase in empowerment score and 0% reliable decrease compared to 17% reliable increase and 21% reliable decrease in the control group. The experimental group showed 19% reliable increase and 4% reliable decrease. CONCLUSIONS: These findings tentatively suggest that self-monitoring to complement standard antidepressant treatment may increase patients' feelings of empowerment. Further research is necessary to investigate long-term empowering effects of self-monitoring in combination with person-tailored feedback.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma.

For patients with diffuse large B cell lymphoma without the involvement of the CNS, the addition of rituximab to standard chemotherapy has significantly improved survival. In this single-center, retrospective analysis, a total of 81 primary CNS lymphoma (PCNSL) patients treated in our institution between 2000 and 2011 were included. Beside first-line chemotherapy with or without rituximab, we evaluated the impact of age (≤/>60 years), autologous stem cell transplantation (ASCT +/-), and other factors upon overall survival (OS) and progression-free survival (PFS). In patients treated with rituximab (n = 27), 3-year OS was 77.8 % (95 % confidence interval (CI) 62-93 %). In contrast, in patients treated without rituximab (n = 52), 3-year OS was only 39.9 % (CI 27-53 %, Fig. 1). The difference in OS was significant in the univariate (p = 0.002) as well as in the multivariate analysis (p = 0.049, hazard ratio (HR) = 0.248). Patients ≤60 years of age (n = 28) had a 3-year OS of 78.2 % (CI 63-94 %); in patients >60 years (n = 51), 3-year OS was 38.7 % (CI 25-52 %). Patients who received high-dose therapy and ASCT had a 3-year OS of 85.2 % (CI 72-99 %), and 65.1 % were alive up to the time of analysis (range 9-131 months). Without ASCT, median OS was only 16 months (CI 11-21) and 3-year OS was 35.2 % (CI 22-48 %). Age and ASCT were significantly associated with better OS in univariate (p = 0.002 and p < 0.001) as well in multivariate analysis (p = 0.004, HR = 0.023 and p = 0.001, HR = 0.014). Rituximab treatment, ASCT, and age are independent prognostic factors for OS in the first-line treatment of PCNSL.

Prospectively recorded and MedDRA-coded safety data of intravenous methylprednisolone therapy in Graves' orbitopathy.

CONTEXT: Safety of intravenous (IV) steroid pulses in patients with Graves' orbitopathy (GO) is still controversial while steroid dose and treatment application have not been finalized. Frequency, severity and characterization of adverse events (AE) were prospectively analyzed. SETTING: Academic referral orbital center with a joint thyroid-eye clinic. PATIENTS: Eighty consecutive and unselected patients with active and severe GO. METHODS: During an established treatment with IV methylprednisolone (cumulative dose 4.5 g) occurring AE were prospectively coded according to the standardized and recognized medical dictionary for regulatory activities (MedDRA). Outcome and severity of AE were documented. AEs judged as at least possibly related to drug treatment were graded as side effect (SE). AEs matching a seriousness criteria as defined by the ICH guideline E6 (good clinical practice) were graded as serious. RESULTS: A total of 38.75% (31/80) of the treated GO patients reported at least one AE while 18 patients (22.5%) reported at least one SE. All SE were within the safety profile of IV methylprednisolone; 31/32 SE (96.87%) were mild-moderate and reversible and only 1/80 patient (1.25%) stopped steroid treatment due to exacerbation of her depression. Most AE were accessory symptoms of the underlying disease and a few only were directly related to IV steroids. Most AEs (90.6%) were graded as mild. Only six patients (7.5%) were hospitalized, three of them due to a dysthyroid optic neuropathy. CONCLUSIONS: Prospective and standardized evaluation with MedDRA and the ICH guideline demonstrated the good pharmacological tolerance and low morbidity of this moderate steroid regimen.

Endochondral fracture healing with external fixation in the Sost knockout mouse results in earlier fibrocartilage callus removal and increased bone volume fraction and strength.

Sclerostin deficiency, via genetic knockout or anti-Sclerostin antibody treatment, has been shown to cause increased bone volume, density and strength of calluses following endochondral bone healing. However, there is limited data on the effect of Sclerostin deficiency on the formative early stage of fibrocartilage (non-bony tissue) formation and removal. In this study we extensively investigate the early fibrocartilage callus. Closed tibial fractures were performed on Sost(-/-) mice and age-matched wild type (C57Bl/6J) controls and assessed at multiple early time points (7, 10 and 14days), as well as at 28days post-fracture after bony union. External fixation was utilized, avoiding internal pinning and minimizing differences in stability stiffness, a variable that has confounded previous research in this area. Normal endochondral ossification progressed in wild type and Sost(-/-) mice with equivalent volumes of fibrocartilage formed at early day 7 and day 10 time points, and bony union in both genotypes by day 28. There were no significant differences in rate of bony union; however there were significant increases in fibrocartilage removal from the Sost(-/-) fracture calluses at day 14 suggesting earlier progression of endochondral healing. Earlier bone formation was seen in Sost(-/-) calluses over wild type with greater bone volume at day 10 (221%, p<0.01). The resultant Sost(-/-) united bony calluses at day 28 had increased bone volume fraction compared to wild type calluses (24%, p<0.05), and the strength of the fractured Sost(-/-) tibiae was greater than that that of wild type fractured tibiae. In summary, bony union was not altered by Sclerostin deficiency in externally-fixed closed tibial fractures, but fibrocartilage removal was enhanced and the resultant united bony calluses had increased bone fraction and increased strength.

Mechanical load increases in bone formation via a sclerostin-independent pathway.

Sclerostin, encoded by the Sost gene, is an important negative regulator of bone formation that has been proposed to have a key role in regulating the response to mechanical loading. To investigate the effect of long-term Sclerostin deficiency on mechanotransduction in bone, we performed experiments on unloaded or loaded tibiae of 10 week old female Sost-/- and wild type mice. Unloading was induced via 0.5U botulinum toxin (BTX) injections into the right quadriceps and calf muscles, causing muscle paralysis and limb disuse. On a separate group of mice, increased loading was performed on the left tibiae through unilateral cyclic axial compression of equivalent strains (+1200 µe) at 1200 cycles/day, 5 days/week. Another cohort of mice receiving equivalent loads (-9.0 N) also were assessed. Contralateral tibiae served as normal load controls. Loaded/unloaded and normal load tibiae were assessed at day 14 for bone volume (BV) and formation changes. Loss of BV was seen in the unloaded tibiae of wild type mice, but BV was not different between normal load and unloaded Sost-/- tibiae. An increase in BV was seen in the loaded tibiae of wild type and Sost-/- mice over their normal load controls. The increased BV was associated with significantly increased mid-shaft periosteal mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS), and endosteal MAR and BFR/BS. Notably, loading induced a greater increase in periosteal MAR and BFR/BS in Sost-/- mice than in wild type controls. Thus, long-term Sclerostin deficiency inhibits the bone loss normally induced with decreased mechanical load, but it can augment the increase in bone formation with increased load.

Physicochemical compatibility of nebulizable drug admixtures containing colistimethate and tobramycin.

Inhalation therapy with nebulizable antibiotic drugs is a mainstay in treating Pseudomonas aeruginosa infections in cystic fibrosis patients. The combination of tobramycin and colistin was found to be superior to monotherapy in killing P. aeruginosa in biofilms. The simultaneous inhalation of tobramycin and colistin might be an option to increase the compliance of patients. The objective of this in-vitro study was to determine whether admixtures of inhalation solutions containing colistin methanesulfonate (CMS) and tobramycin are physicochemically compatible. Physical compatibility was determined by measuring pH and osmolality. Chemical compatibility was determined by testing the antibiotic activity of the mixtures by the pharmacopoeial microbiological assay and comparing the results to those of standard solutions. Samples were analyzed immediately after mixing and after 24 h. Values of pH and osmolality remained unchanged and in physiologically acceptable ranges. Neither for colistin methanesulfonate (CMS) nor for tobramycin losses of antibiotic potency were registered at any time. Admixtures of nebulizer solutions containing CMS and tobramycin were shown to be physicochemically compatible. Further investigations are needed to determine whether drug delivery is affected by mixing the nebulizer solutions to ensure that simultaneous inhalation is recommendable.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Increased medication compliance of liver transplant patients switched from a twice-daily to a once-daily tacrolimus-based immunosuppressive regimen.

BACKGROUND: Compliance with immunosuppressive therapy plays a major role in the long-term success of liver transplantation. Thus, the development of strategies to promote compliance of liver transplant patients and its evaluation over time are of particular interest. OBJECTIVE: The main objective of this study was to compare medication compliance rates among liver transplant patients over time after transplantation where switched from a twice- to once-daily tacrolimus-based regimen. METHODS: Sixty-five liver transplant patients being administered tacrolimus-based therapy were classified into three subgroups with regard to time posttransplantation. Medication compliance with tacrolimus-based therapy was measured using an electronic medication event monitoring system over a 12-month period: for 6 months tacrolimus was administered twice-daily and for 6 months, once-daily. Dosing, taking, and timing compliance as well as drug holidays were compared intra-individually between twice- and once-daily intake and among the three subgroups. In addition, patient compliance and quality of life were evaluated using questionnaires. RESULTS: A per protocol analysis of electronically obtained data showed 63 patients to be eligible. The resulting dosing, taking, and timing compliance rates of the patients were higher during the once-daily dosing period. No significant differences in compliance rates with tacrolimus therapy were observed among three subgroups independent of the dosing regimen. More patients failed the correct timing of the evening compared to the morning dose. Missing doses occurred particularly during weekends. Compliance variables measured by questionnaires (Morisky score, self-report, Medication Experience Scale for Immunosuppressants (MESI) score) and the Hospital Anxiety and Depression Scale score were similar in the two dosing periods. The short-form health survey (SF-36) score was higher with once-daily intake. CONCLUSION: The high measured compliance rates did not vary significantly dependent upon the time after transplantation. Nevertheless, compliance rates were greater using once-daily tacrolimus dosing.

[The dilemma of discharge medication. A multicentre cohort study on distribution of discharge medication and counseling by the hospital pharmacist in comparison to current practice]. / Das Dilemma der Entlassungsmedikation. Eine multizentrische Kohortenstudie zur Mitgabe und Beratung durch den Krankenhausapotheker im Vergleich zur aktuellen Praxis.

BACKGROUND: Today medication gaps are inevitable at discharge from the hospital and patients are insufficiently educated about their medication. METHODS: The rate of medication gaps and extent and quality of medication counseling were investigated in a prospective comparative study at five different hospitals. In a consecutive manner 847 patients were observed using current practice and 618 patients with a hospital pharmacist involved. Perception of patients, their general practitioners (GP) and community pharmacists with the different discharge procedures was analyzed by meansof questionnaires. RESULTS: Using current practice 24% of patients missed newly prescribed drugs at discharge. Medication gaps occurred according to patients'or GPs'reports in 10% or 22% of patients, respectively. 12% of patients were neither educated in the hospital nor in private setting about their medication. 22% of patients were not or only partially satisfied with the information received. Patient education, supported by a medication schedule and distribution of discharge medication by hospital pharmacists proved to be feasible and beneficial for patients and GPs. Medication gaps were significantly reduced to 4%. All patients received medication counseling at discharge and quality of education significantlyimproved. CONCLUSION: Distribution of discharge medication and counseling of patients bya hospital pharmacist are suitable measures in order to bridge medication and information gaps. Changes in healthcare legislation are necessary in order to implement the hospital pharmacy service.

Unexpected stability of Bacteroidetes and Firmicutes communities in laboratory biogas reactors fed with different defined substrates.

In the present study, bacterial communities in 200-liter biogas reactors containing liquid manure consecutively fed with casein, starch, and cream were investigated over a period of up to 33 days. A 16S rRNA gene clone library identified Bacteroidetes and Firmicutes as the most abundant bacterial groups in the starting material, at 58.9% and 30.1% of sequences, respectively. The community development of both groups was monitored by real-time PCR and single-strand conformation polymorphism (SSCP) analysis. The Firmicutes and Bacteroidetes communities were unexpectedly stable and hardly influenced by batch-feeding events. The continuous feeding of starch led to community shifts that nevertheless contributed to a stable reactor performance. A longer starving period and a change in the pH value resulted in further community shifts within the Bacteroidetes but did not influence the Firmicutes. Predominant DNA bands from SSCP gels were cloned and sequenced. Sequences related to Peptococcaceae, Cytophagales, and Petrimonas sulfuriphila were found in all samples from all experiments. Real-time PCR demonstrated the abundance of members of the phylum Bacteroidetes and also reflected changes in gene copy numbers in conjunction with a changing pH value and acetate accumulation.

Evidence that genes for depression impact on the pathway from trauma to psychotic-like symptoms by occasioning emotional dysregulation.

BACKGROUND: Genes for depression may act by making individuals more sensitive to childhood trauma. Given that childhood adversity is a risk factor for adult psychosis and symptoms of depression and psychosis tend to cluster within individuals and families, the aim was to examine whether the association between childhood adversity and psychotic-like symptoms is moderated by genetic liability for depression. A secondary aim was to determine to what degree a depression-related increase in stress sensitivity or depressive symptoms themselves occasioned the moderating effect. METHOD: Female twins (n=508) completed both prospective and retrospective questionnaires regarding childhood adversity [the Symptom Checklist-90 - Revised (SCL-90-R) and SCID-I (psychotic symptoms)] and psychotic trait liability [the Community Assessment of Psychic Experiences (CAPE)]. Stress sensitivity was indexed by appraisals of event-related stress and negative affect (NA) in the flow of daily life, assessed with momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of childhood adversity by genetic liability for depression in the prediction of follow-up psychotic experiences. RESULTS: The effect of childhood adversity was significantly moderated by genetic vulnerability for depression in the model of both follow-up psychotic experiences (SCL-90-R) and follow-up psychotic trait liability (CAPE). The moderation by genetic liability was mediated by depressive experience but not by stress sensitivity. CONCLUSIONS: Genetic liability for depression may potentiate the pathway from childhood adversity to psychotic-like symptoms through dysfunctional emotional processing of anomalous experiences associated with childhood trauma.

Momentary assessment technology as a tool to help patients with depression help themselves.

OBJECTIVE: Given high relapse rates and residual symptoms in depression, new strategies to increase treatment effectiveness are required. A promising avenue is to investigate how electronic momentary assessment technology may contribute to clinical assessment and interventions in depression. METHOD: A literature search was conducted focusing on the potential contribution of momentary assessments to clinical applications in depression. RESULTS: Momentary assessments are able to reveal subtle, small but repetitive and relevant patterns of emotional expression that predict future course of depression. A momentary assessment tool may expose manageable pieces of daily life behaviour contributing to the depressive experience that patients can influence. The use of this explicit knowledge of daily life experience is understudied with regard to its contribution to diagnostic assessment, monitoring of treatment effects and feedback interventions in depressed patients. The clinical application of momentary assessments may stimulate a shift from passive consumption of treatment to an active role for patients in their recovery and increased patient ownership. CONCLUSION: The precise, prospective and fine-grained information that momentary assessment technology provides may contribute to clinical practice in various ways. Future studies should examine the clinical impact of its use and the feasibility of its implementation in mental health care.

[Partial weight-bearing in rehabilitation. Strategies for instruction and limitations]. / Teilbelastung in der Rehabilitation. Vermittlungsstrategien und Grenzen.

Following trauma or surgery on the musculoskeletal system the primary aim is always as complete a restitution of mobility as possible. By mobilization with partial weight-bearing this is possible. The preferred way of teaching partial weight-bearing is the use of conventional bathroom scales. This method proves to be simple as well as time and cost-saving, but the transferability to the patient's daily life is questionable. Training and control of partial weight-bearing under dynamic conditions, such as normal walking, and walking up and down stairs seem to be very important. Different investigations have shown that the minority of subjects recruited could manage to maintain the given load of partial weight-bearing. Furthermore, the actual resulting moments within the joints, caused by muscles, fascia and tendons, are not considered in presets of partial weight-bearing, as only external forces (ground reaction forces) are measured. However, the problems in teaching partial weight-bearing have to be contrasted with the as yet unexplained issue of postoperative partial versus full weight-bearing.

Pharmacy and pharmacology of biosimilars.

Biosimilar medicines are biological medicinal products that can obtain a marketing authorization in the EU after the original product (biological reference medicine) has run out of patent. As a prerequisite, studies including clinical trials are to be conducted to compare the quality, safety, and efficacy of the biosimilar and reference medicine. Due to the specific characteristics of biopharmaceuticals like complex 3-dimensional (glyco) protein structure, immunogenicity, production in living organisms, which causes heterogeneity, complex manufacturing process and analysis, interchangeability of the biosimilar with its reference drug product is not guaranteed. In addition, INN (international non-proprietary name) naming and interchangeability, pharmacovigilance, and traceability are subjects for discussion. The aim of this article is to describe the pharmaceutical and pharmacological specialties of biosimilars and to inform about points to consider (like manufacturer, good handling practice, pharmacovigilance, costs), when the use of biosimilars comes into question.