Potential utility of new surgical hemostatic film using Hydrofit®: a preliminary study

Journal of Artificial Organs - We developed a surgical hemostatic film using Hydrofit® (Hydrofit® film). This film is prepared by reacting Hydrofit® with water in advance, and it can...     

Influence of the clindamycin administration route on the magnitude of clindamycin–rifampicin interaction: a prospective pharmacokinetic study

ObjectivesAn important clindamycin–rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration.MethodsPatients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin–rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2–6 weeks, followed by an oral regimen. Liquid chromatography–mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route.ResultsComparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC_0–8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively.ConclusionThe magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin–rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.     

BiovaxID®: a customized idiotype vaccine for the treatment of B-cell lymphoma

Most patients with B-cell lymphoma face an often incurable disease, particularly those diagnosed with an indolent subtype. The addition of passive immunotherapy to old and new chemotherapy regimens has improved both response rates and disease-free survival, leading in many cases to an extended overall survival. However, a cure remains elusive in most cases. For this reason, the patient- and tumor-specific idiotype, that is the collection of epitopes exclusively presented by the tumor clone's surface immunoglobulin, has been extensively studied as a privileged target for vaccine therapy, aiming at preventing disease re-occurrence after standard treatment. BiovaxID(?) (Biovest International, FL, USA), the most clinically advanced among such therapeutic vaccines, finds itself at a crucial turning point when it comes to further development. Both clinical trials in which it has been formally employed have shown intriguing results. Independent studies using slightly different versions of a conceptually identical vaccine provided all proofs of principle required to ascertain the vaccine's value - biological and clinical efficacy as well as clinical benefit. However, all these data have failed to bring an idiotype vaccine to the market owing to reasons that often have very little to do with the product itself. In fact, some successful studies were not conceived with this goal in mind, while others simply did not enroll enough patients to convincingly make their case for regulatory approval. It is likely that one or more new clinical trials will have to be successfully completed to reach the ultimate goal - that is, to make BiovaxID available to most patients and to adequately position it in the very crowded therapeutic algorithm of B-cell lymphoma.     

Butox® 7.5 pour on: a deltamethrin treatment of sheep and cattle: pilot study of killing effects on Culicoides species (Ceratopogonidae)

Topical treatment (at the neck and along the vertebral column) with deltamethrin (Butox 7.5 pour on) of cattle (30 ml/400-kg body weight) and sheep (10 ml/60-kg body weight) was done to find out, whether the insecticide may reach in a sufficient dosage the legs, which are known to be the main biting site of Culicoides specimens that are the vectors of the recently introduced Bluetongue virus in central Europe. At days 7, 14, 21, 28, and 35 after treatment, some hair was cut off from the legs--close to the claws. Freshly (the night before) caught Culicoides obsoletus specimens were then exposed for 15, 30, 60, or 120 s to such hair and afterwards transferred to a filter paper within plastic Petri dishes to observe their fate. It turned out that even a short contact of 15 s of the Culicoides specimens with deltamethrin-treated hair of cattle or sheep was sufficient to paralyze and kill Culicoides specimens within a reasonable short time even when the hair were cut off at day 28 after treatment. While the results obtained in cattle and sheep were rather similar for days 7 and 14 after treatment, the speed of the killing effect of treated hair of cattle on Culicoides considerably slowed down beginning from day 21 after treatment. However, all the experiments clearly showed that the insecticide deltamethrin may reach the feet of cattle and may kill Culicoides specimens when the product is poured along the vertebral column. Such a treatment may considerably reduce the risk of transmission of the agents of disease. However, in the case of the thick fleece of sheep, the insecticide must be poured directly into the skin to reach full activity.     

Assessment criteria for evaluating the stability and position of the centre of gravity on a balance training platform: a simulation with Matlab®

The anterior-posterior and medial-lateral tipping values of a training platform within the scope of a balance training activity should be evaluated in regard to position and the changing position of the centre of gravity (COG). Data streams are simulated and modulated with the help of the signal processing programme Matlab?. These data streams are evaluated using existing balance formulas and a specially developed formula. Active Balance Index referring to the zero point (ABI(0)) allows an assertion about the magnitude of the mean tipping angle with the magnitude origin in the centre of the training platform. Active Balance Index referring to the arithmetical mean COG (ABI(mean)) enables an assertion about the mean tipping angle with the magnitude origin in the COG mean position. The deviation of the mean COG from absolute balance which is projected onto the platform is calculated by the Active Balance Ratio (ABR). The Active Balance Index (ABI) in combination with the ABR seems to be an adequate parameter for the evaluation of COG stability on a training platform.     

Assessment criteria for evaluating the stability and position of the centre of gravity on a balance training platform: a simulation with Matlab®

The anterior–posterior and medial–lateral tipping values of a training platform within the scope of a balance training activity should be evaluated in regard to position and the changing position of the centre of gravity (COG). Data streams are simulated and modulated with the help of the signal processing programme Matlab®. These data streams are evaluated using existing balance formulas and a specially developed formula. Active Balance Index referring to the zero point (ABI₀) allows an assertion about the magnitude of the mean tipping angle with the magnitude origin in the centre of the training platform. Active Balance Index referring to the arithmetical mean COG (ABI_mean) enables an assertion about the mean tipping angle with the magnitude origin in the COG mean position. The deviation of the mean COG from absolute balance which is projected onto the platform is calculated by the Active Balance Ratio (ABR). The Active Balance Index (ABI) in combination with the ABR seems to be an adequate parameter for the evaluation of COG stability on a training platform.     

Influence of test time on results of the impedance aggregometer Multiplate® analyser in dogs

The Multiplate® analyser is a relatively new impedance aggregometer designed for human medicine but was recently evaluated for canine blood. The aim of this study was to determine the influence of test time (i.e. measuring period) on reference values and the validity of measurement results in canine blood. Based on blood samples of 83 healthy dogs, reference values for different test times (6, 8, 10 and 12 min) were established for area under the curve (AUC) and maximum aggregation values for adenosine diphosphate (ADP)-, collagen- and arachidonic acid-induced aggregation. The results of 134 samples of 117 dogs with various diseases and eight samples with reduced platelet function owing to treatment with the platelet aggregation inhibitor clopidogrel were calculated for different test times and classified as decreased, normal or increased. Maximum aggregation and AUC values increased significantly with increasing test time. Chi square test did not show significant differences between the various test times with regard to the number of increased and decreased measurement results for any agonist. All samples of dogs treated with clopidogrel and measured with the agonist ADP revealed decreased AUC values at any time point. The results of our study indicate that test time significantly influences AUC and maximum aggregation values but has limited influence on sensitivity of measurement results of canine blood using the investigated instrument.     

Contribution of the FilmArray® Gastrointestinal Panel in the laboratory diagnosis of gastroenteritis in a cohort of children: a two-year prospective study

This study represents a 2-year picture of the epidemiology of enteric pathogens in children suffering from gastroenteritis using the FilmArray® Gastrointestinal Panel (FA-GP), a multiplex molecular assay that allows to simultaneously detect a large panel of pathogens independently of the etiological suspicion and to evaluate its potential contribution to the diagnosis compared to the conventional methods.A total of 1716 stool samples, collected from children with clinical suspicion of bacterial and/or viral gastroenteritis attending the University Hospital of Parma, was submitted to the FA-GP and, when an adequate aliquot was available, to electron microscopy (n = 1163) for virus detection and to an enterovirus-targeting real-time PCR (n = 1703). Specimens with positive results for Salmonella, Yersinia enterocolitica, Vibrio, diarrheagenic Escherichia coli/Shigella, Campylobacter, Plesiomonas shigelloides and/or parasites by the FA-GP were also submitted to conventional diagnostic methods.The FA-GP gave positive results in 958 (55.8%) cases, 64.8% from inpatients: 647 (67.5%) contained a single agent and 311 (32.5%) multiple agents, for a total of 1374 pathogens. Enteropathogenic E. coli, rotavirus, norovirus, toxigenic Clostridioides difficile, and sapovirus were the most commonly detected pathogens. A total of 812 additional agents (344 of which as single pathogen) was detected by the FA-GP and not included in the clinical suspicion. The overall recovery rate of the conventional methods from stools that resulted positive by the FA-GP was 38.6% for bacteria, 50% and 84.2% for Giardia intestinalis and Cryptosporidium, respectively, and ranged from 3.7% to 64.6% for viruses, if excluding all electron microscopy-negative astroviruses. Enterovirus, an agent not targeted by the FA-GP, was revealed in 9.6% (164/1703) of the examined samples, and in 52 cases it was the only agent detected.The results of this study allowed to extend the range of detectable pathogens independently of the clinical suspicion, to detect co-infections in almost one third of children positive for at least one agent and to show that conventional methods would have missed more than half of the enteric agents detected by the FA-GP.     

The Influence of Interleukin-32γ on Osteoclastogenesis with a Focus on Fusion-Related Genes

We previously reported that interleukin-32 gamma (IL-32γ) has a direct effect on osteoclast differentiation and activation in vitro in the context of receptor activator of NF-κB ligand (RANKL) co-stimulation. However, the stage of osteoclast differentiation at which IL-32γ exerts its effect was not determined. Here, we demonstrated that IL-32γ plays an important role in the fusion of preosteoclasts to yield multinuclear osteoclasts, particularly large osteoclasts. The synergistic effect of IL-32γ on RANKL-induced formation of multinuclear osteoclasts was readily apparent when cells were treated with IL-32γ at the fusion stage. In addition, we demonstrated that IL-32γ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and NFATc1 inactivation by cyclosporine treatment attenuated the effect of IL-32γ. These results indicate that IL-32γ is a potential mediator of osteoclast fusion, likely through up-regulation of NFATc1 and DC-STAMP.     

Influence of primary care practices on patients’ uptake of diabetic retinopathy screening: a qualitative case study

Background

The NHS Diabetic Eye Screening Programme aims to reduce the risk of sight loss among people with diabetes in England by enabling prompt diagnosis of sight-threatening retinopathy. However, the rate of screening uptake between practices can vary from 55% to 95%. Existing research focuses on the impact of patient demographics but little is known about GP practice-related factors that can make a difference.

Aim

To identify factors contributing to high or low patient uptake of retinopathy screening.

Design and setting

Qualitative case-based study; nine purposively selected GP practices (deprived/affluent; high/low screening uptake) in three retinopathy screening programme areas.

Methods

Semi-structured interviews were conducted with patients, primary care professionals, and screeners. A comparative case-based analysis was carried out to identify factors related to high or low screening uptake.

Results

Eight possible factors that influenced uptake were identified. Five modifiable factors related to service and staff interactions: communication with screening services; contacting patients; integration of screening with other care; focus on the newly diagnosed; and perception of non-attenders. Three factors were non-modifiable challenges related to practice location: level of deprivation; diversity of ethnicities and languages; and transport and access. All practices adopted strategies to improve uptake, but the presence of two or more major barriers made it very hard for practices to achieve higher uptake levels.

Conclusions

A range of service-level opportunities to improve screening attendance were identified that are available to practices and screening teams. More research is needed into the complex interfaces of care that make up retinopathy screening.     

Validity of rotational laxity coupled with anterior translation of the knee: A cadaveric study comparing radiostereometry and the Rotab®

Background

In current practice, anterior cruciate ligament (ACL) tears can be diagnosed using several devices to measure anterior tibial translation and rotational knee laxity, but these measures are never collected together. The Rotab®, which yields simultaneous measurements of anterior tibial translation and passive lower limb rotation under stress, would therefore be advantageous in current practice, but its reliability has never been tested.

Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study

Background

The standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol® and its in vivo mechanism of action in OA patients.

Methods

Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol® twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients’ chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples.

Results

The oral intake of Pycnogenol® downregulated the gene expression of various cartilage degradation markers in the patients’ chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤?0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p?≤?0.05) after three weeks intake of the pine bark extract.

Conclusions

This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol® on symptom scores of patients suffering from OA.

Trial registration

ISRCTN10754119. Retrospectively registered 08/10/2015.

     

Effects of altitude on the energetics of human best performances in 100 m running: a theoretical analysis

The present study was designed to investigate the role of reduced air density on the energetics of 100 m running at altitude. A mathematical supply-demand model was used where supply had two components, aerobic and anaerobic and demand had three components: the cost of overcoming non-aerodynamic forces (C_na), the cost of overcoming air resistance (C_aero), and the cost due to changes in the runner's kinetic energy (C_kin). Actual instantaneous-speed curves recorded in 100 m world champions were modelled at sea level. Then I calculated improvements in 100 m running times and changes in the components of the energy cost with changes in altitude from 0 m to 4,000 m. For the 100 m world championship for men, the model predicted times of 9.88 s at sea level, 9.80 s at 1,000 m, 9.73 s at 2,000 m, 9.64 s at 4,000 m and 9.15 s in the hypothetical situation where the air resistance was nil. In the counterpart for women the corresponding times were 10.85 s, 10.76 s, 10.70 s, 10.60 s and 10.04 s. The C_aero was 12%–13% of demand at sea level, 10%–11% at 2,000 m and 8%–9% at 4,000 m. When C_aero decreased this led to better performance by making more energy available for acceleration. Accordingly, C_kin increased from 20%–24% at sea level to 23%–27% at 4,000 m. There was no effect of altitude specific to body size. Electronic Publication     

Influence of sample storage on impedance aggregometry measured using the Multiplate® analyser in dogs

Whole blood impedance aggregometry is an important method to investigate platelet function disorders. Storage time is regarded as a main pre-analytical factor. The objective of the present study was to evaluate the influence of storage time of canine hirudin-anticoagulated blood on test results of different parameters (area under the curve (AUC), maximum aggregation and velocity) of impedance aggregometry. Hirudin-anticoagulated blood from eight healthy dogs and eight samples collected from two dogs receiving clopidogrel treatment (4 mg/kg orally once daily) were stored at room temperature for 1 day. The samples were tested at different times (0.5, 1, 2, 3, 4, 6, 8, 24 h). Samples of normal dogs were activated using 10 μmol/L adenosine diphosphate (ADP), 5 μg/mL collagen or 1 mmol/L arachidonic acid (AA), whereas in clopidogrel-treated dogs only ADP was used. Analysis of variance revealed significant differences between time points for collagen-induced aggregation in healthy dogs (maximum aggregation, velocity), AA-induced aggregation in healthy dogs (AUC, maximal aggregation) and ADP-induced aggregation in clopidogrel-treated dogs (maximum aggregation, velocity) (p?相似文献   

Women’s perspectives on postpartum depression screening in pediatric settings: a preliminary study

This preliminary study is the first to identify mothers’ perspectives on barriers and facilitators to addressing postpartum depression (PPD) in pediatric settings. We conducted four 90-min focus groups with women (n?=?27) who self-identified a history of perinatal depression and/or emotional complications. Barriers reported included stigma and fear among women and lack of provider knowledge/skills regarding depression. Participants recommended non-stigmatizing approaches to depression screening/referral. Future PPD screening efforts should leverage the pediatrician–mother relationship to mitigate mothers’ fears and encourage help-seeking.     

In-patient treatment of mothers with depressive disorders - does joint admission of their children have a negative effect on the results of treatment?

BACKGROUND: There is disagreement whether in-patient psychotherapeutic treatment results for women whose children are cohospitalised with them would be better if the mothers were hospitalised without children. The purpose of this study was to examine this question in the case of mothers with depressive symptoms. METHODS: The treatment results for 43 female in-patients (21 with and 22 without accompanying children) in a prospective, randomised, controlled study were compared. The period of observation was 6 weeks. The Beck Depression Inventory (BDI) and the Changes in Experience and Behaviour Questionnaire (VEV) were used for outcome measures. RESULTS: At 6 weeks, according to the intent-to-treat principle, neither the VEV (p = 0.58) nor the BDI (p = 0.57) yielded significant differences between mothers whose children were admitted jointly and mothers whose children were not. CONCLUSION: The treatment results for patients with depressive symptoms whoare accompanied by their children for the duration of their in-patient psychotherapy treatment are just as good as those for mothers whose children are not jointly admitted. Additionally, the data have further implications that lend themselves to discussion regarding support for this type of facility.