Reduced risk of serious pneumococcal infections up to 10 years after a dose of pneumococcal conjugate vaccine in established arthritis.

BACKGROUND: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. METHODS: In total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. RESULTS: Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. CONCLUSION: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.

Laser-induced ultrasound transmitters for large-volume ultrasound tomography.

We present a protocol for the design, fabrication and characterisation of laser-induced ultrasound transmitters with a specific, user-defined frequency response for the purpose of ultrasound tomography of large-volume biomedical samples. Using an analytic solution to the photoacoustic equation and measurements of the optical and acoustic properties of the materials used in the transmitters, we arrive at a required mixture of carbon black and polydimethylsiloxane to achieve the desired frequency response. After an in-depth explanation of the fabrication and characterisation approaches we show the performance of the fabricated transmitter, which has a centre frequency of 0.9 MHz, 200% bandwidth and 45.8 ∘ opening angle, multi-kPa pressures over a large depth range in water.

Risk factors for cefepime nonsusceptible Gram-negative infections in allogeneic hematopoietic cell transplant recipients.

PURPOSE: Allogeneic hematopoietic cell transplant recipients undergo myelosuppressive chemotherapy to allow engraftment of stem cells and are at particularly high risk for bacterial infections and adverse outcomes. Patients undergoing hematopoietic cell transplant are at increased risk for healthcare-associated infections, including infections with multidrug-resistant pathogens. Cefepime is a commonly prescribed antibiotic for empiric therapy in hematopoietic cell transplant patients, but there is minimal data describing cefepime resistance rates, risk factors for resistance, and clinical outcomes associated with cefepime-resistant infections. METHODS: Adult (≥18 years old) allogeneic hematopoietic cell transplant recipients with a culture positive for a gram-negative rod between January 2010 and January 2016 were spilt into two groups: cefepime susceptible and cefepime nonsusceptible . The primary objective of this study was to identify risk factors for cefepime nonsusceptible through multivariable logistic regression. RESULTS: A total of 107 patients were included (27 cefepime nonsusceptible, 80 cefepime-susceptible), yielding a 25.2% nonsusceptibility rate. Multivariable analysis yielded age >60 years old, Klebsiella spp. infection, Acinetobacter spp. infection, healthcare exposures within 90 days, acute gastrointestinal graft-vs-host-disease, and chronic graft-vs-host-disease at multiple locations as significant risk factors for cefepime nonsusceptible. The receiver operating characteristic area under the curve of the model was 0.851. Thirty-day all-cause mortality (29.6% versus 16.3%, p = 0.13) and length of hospitalization (19 versus 12.5 days, p = 0.0650) were numerically higher in the cefepime nonsusceptible group. CONCLUSIONS: Hematopoietic cell transplant patients with acute gastrointestinal graft versus host disease, extensive chronic graft-vs-host-disease, advanced age, previous healthcare exposures, or infections with Klebsiella and Acinetobacter are at increased risk for cefepime nonsusceptible. Patients infected with cefepime nonsusceptible pathogens may have higher rates of mortality and length of hospitalization.

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody response to 13-valent conjugated pneumococcal vaccine.

Cascaded gain fibers for increasing output power and the stimulated Brillouin scattering threshold of narrow linewidth fiber Raman amplifiers.

We show both experimentally and theoretically a method to increase the stimulated Brillouin scattering (SBS) threshold and output power of narrow linewidth fiber Raman amplifiers. This method employs two or more fibers with varying concentrations of the Raman gain material dopant such as GeO2 or P2O5 in silicate-based glasses. These fibers are then cascaded to form an amplifier gain stage, disrupting the buildup of SBS that normally occurs in single continuous fibers. The numerical model shown is applicable to arbitrary amplifier systems for gain stage optimization and increased power scaling. We give experimental results for phosphosilicate fibers that agree well with simulation predictions that support the numerical model used.

Dynamic weight bearing as a non-reflexive method for the measurement of abdominal pain in mice.

BACKGROUND: Chronic pelvic pain (CPP) is a high burden for patients and society. It affects 15-24% of women in reproductive age and is an area of high unmet medical need. CPP can be caused by a wide range of visceral diseases such as abdominal infections, gastrointestinal or gynaecological diseases like endometriosis. Despite the high medical need for this condition, pharmacological approaches are hampered by the limited number of available methods for the behavioural evaluation of pain in inflammation-driven animal models of pelvic pain. METHODS: The dynamic weight bearing (DWB) system was used for the evaluation of spontaneous behaviour changes in the zymosan-induced peritonitis mouse model. Inflammatory mediator levels were evaluated in peritoneal lavage and their correlation with the behavioural endpoints was assessed. We evaluated the effect on behavioural endpoints of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib and the Nav 1.8 blocker A-803467. RESULTS: The presence of a relief posture, characterized by a significantly increased weight distribution towards the front paws, was observed following intraperitoneal injection of zymosan. A positive correlation was detected between PGE2 levels in the peritoneal lavage and DWB endpoints. In addition, zymosan-induced weight bearing changes were reverted by celecoxib and A-803467. CONCLUSIONS: This study described for the first time the use of DWB as a non-subjective and non-reflexive method for the evaluation of inflammatory-driven abdominal pain in a mouse model.

The risk of pneumococcal infections after immunization with pneumococcal conjugate vaccine compared to non-vaccinated inflammatory arthritis patients.

OBJECTIVES: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. METHOD: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagnostic codes. The following infections were considered as serious cases: pneumonia, other lower respiratory infections, meningitis, sepsis, and septic arthritis. The relative risk (RR) of infection was calculated as the number of events after/number of events before vaccination. Ratios of relative risk (RRRs) were calculated between vaccinated and non-vaccinated groups of patients. A generalized estimating equation (GEE) was used to handle correlated data for several events in the same individual. RESULTS: Although statistically non-significant, the point estimate of the RRR [0.55, 95% confidence interval (CI) 0.25-1.22] suggested a reduced risk of serious pneumococcal infections in vaccinated patients compared to the unexposed group. CONCLUSIONS: Vaccination with PCV7 tended to reduce the risk of putative serious pneumococcal infections by about 45% compared to non-vaccinated patients in this observational cohort study.

[Current progress of the artificial accommodation system]. / Fortschritte des Künstlichen Akkommodationssystems.

In case of presbyopia or cataract the "artificial accommodation system" represents one future possibility to durably restore the ability to accommodate. The work presented describes recent progress in the development of the artificial accommodation system. Major advances were achieved in the fields of the actuator system for the active optics, the pupil near reflex sensor, the communication system, the power supply system as well as in system integration. Beside the technical advances, first trials were performed to implant the artificial accommodation system into animals. These trials showed that the new lens shaped design and the C-shaped haptics are beneficial for implantation and secure fixation of the implant inside the capsular bag.

Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review.

WHAT IS KNOWN AND OBJECTIVE: Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging. Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity. The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients. However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents. Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients. METHODS: A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based antimicrobial dosing guideline for morbidly obese patients was developed. An analysis of guideline compliance and cost analysis were performed following guideline implementation. RESULTS AND DISCUSSION: This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding. The majority of weight-based antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight. WHAT IS NEW AND CONCLUSION: This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity. A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses. However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity.

Risk factors for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) represents a significant burden on the healthcare system and is associated with poor outcomes in hematopoietic stem cell transplant (HSCT) patients. Data are limited evaluating recurrence rates and risk factors for recurrence in HSCT patients. METHODS: HSCT patients who developed CDI between January 2010 and December 2012 were divided into 2 groups: non-recurrent CDI (nrCDI) and recurrent CDI (rCDI). Risk factors for rCDI were compared between groups. Rate of recurrence in HSCT patients was compared to that in other hospitalized patients. RESULTS: CDI was diagnosed in 95 of 711 HSCT patients (22 rCDI and 73 nrCDI). Recurrence rates were similar in HSCT patients compared with other hospitalized patients (23.2% vs. 22.9%, P > 0.99). Patients in the rCDI group developed the index case of CDI significantly earlier than the nrCDI group (3.5 days vs. 7.0 days after transplant, P = 0.05). On univariate analysis, patients with rCDI were more likely to have prior history of CDI and neutropenia at the time of the index CDI case. Neutropenia at the time of the index CDI case was the only independent predictor of rCDI (78.8 vs. 34.8%, P = 0.006) on multivariate analysis. CONCLUSIONS: The rate of rCDI was similar between HSCT and other hospitalized patients, and the majority of patients developed the index case of CDI within a week of transplantation. Neutropenia at the index CDI case may be associated with increased rates of rCDI.

Reversal mechanism of an individual Ni nanotube simultaneously studied by torque and SQUID magnetometry.

Using an optimally coupled nanometer-scale SQUID, we measure the magnetic flux originating from an individual ferromagnetic Ni nanotube attached to a Si cantilever. At the same time, we detect the nanotube's volume magnetization using torque magnetometry. We observe both the predicted reversible and irreversible reversal processes. A detailed comparison with micromagnetic simulations suggests that vortexlike states are formed in different segments of the individual nanotube. Such stray-field free states are interesting for memory applications and noninvasive sensing.

Less advanced stages of colon cancer in patients with type 2 diabetes mellitus: an unexpected finding?

INTRODUCTION: Epidemiological studies have found an increased risk for colon cancer and faster disease progression in patients with type 2 diabetes mellitus (T2DM). We aimed to determine whether patients with T2DM are diagnosed with more advanced stages of colorectal cancer, i. e., metastasized disease (UICC III and IV), at the time of diagnosis, since such a finding may have an impact on future guidelines for patients with T2DM. MATERIALS AND METHODS: A cross-sectional analysis of colorectal cancer patients was performed. Stages at diagnosis in patients with (18.0%) or without (82%) T2DM were compared using logistic regression analysis to correct for confounders. RESULTS: Patients with T2DM were older, more obese, and more often male (each p<0.05). Unexpectedly, patients with T2DM had a lower risk for metastasized disease at diagnosis (p=0.023). Correction for age, gender, BMI, smoking and aspirin intake in a multiple logistic regression analysis did not change the result (OR=0.57, p=0.037). When looking at individual cancer stages rather than collapsed categories, there was a trend for less advanced stages in patients with T2DM (p=0.093). Excluding stage I because of potential screening bias due to the introduction of (insurance-covered) colonoscopy screening improved model fit, and confirmed less advanced cancer stages (p=0.0246). CONCLUSIONS: Possibly because of earlier detection, patients with T2DM may be at lower risk for advanced stages of colon cancer at diagnosis. Further studies are warranted to confirm our results and to investigate the impact of closer medical surveillance in patients with type 2 diabetes mellitus.

Optimal secondary coil design for inductive powering of the Artificial Accommodation System.

Age-related ailments like presbyopia and cataract are increasing concerns in the aging society. Both go along with a loss of ability to accommodate. A new approach to restore the patients' ability to accommodate is the Artificial Accommodation System. This micro mechatronic system will be implanted into the capsular bag to replace the human crystalline lens. Depending on the patients' actual need for accommodation, the Artificial Accommodation System autonomously adapts the refractive power of its integrated optical element in a way that the projection on the patients' retina results in a sharp image. As the Artificial Accommodation System is an active implant, its subsystems have to be supplied with electrical energy. Evolving technologies, like energy harvesting, which can potentially be used to power an implant like the Artificial Accommodation System are at the current state of art not sufficient to power the Artificial Accommodation System autonomously [1]. In the near future, therefore an inductive power supply system will be developed which includes an energy storage to power the Artificial Accommodation System autonomously over a period of 24 h and can be recharged wirelessly. This Paper describes a new possibility to optimize the secondary coil design in a solely analytical way, based on a new figure of merit. Within this paper the developed figure of merit is applied to optimize the secondary coil design for the Artificial Accommodation System.

[Energy and memory efficient calculation of the accommodation demand in the artificial accommodation system]. / Energie- und speichereffiziente Berechnung des Akkommodationsbedarfs im Künstlichen Akkommodationssystem.

Presbyopia and cataract are gaining more and more importance in the ageing society. Both age-related complaints are accompanied with a loss of the eye's ability to accommodate. A new approach to restore accommodation is the Artificial Accommodation System, an autonomous micro system, which will be implanted into the capsular bag instead of a rigid intraocular lens. The Artificial Accommodation System will, depending on the actual demand for accommodation, autonomously adapt the refractive power of its integrated optical element. One possibility to measure the demand for accommodation non-intrusively is to analyse eye movements. We present an efficient algorithm, based on the CORDIC technique, to calculate the demand for accommodation from magnetic field sensor data. It can be shown that specialised algorithms significantly shorten calculation time without violating precision requirements. Additionally, a communication strategy for the wireless exchange of sensor data between the implants of the left and right eye is introduced. The strategy allows for a one-sided calculation of the demand for accommodation, resulting in an overall reduction of calculation time by 50 %. The presented methods enable autonomous microsystems, such as the Artificial Accommodation System, to save significant amounts of energy, leading to extended autonomous run-times.

Clinical management of clopidogrel inefficiency by point of care platelet function testing and individual adjustment of anti-platelet therapy--initial experiences.

Insufficient inhibition of ADP dependent platelet aggregation by clopidogrel is associated with an increased risk for adverse coronary events, such as stent thrombosis, after percutaneous coronary intervention. Here, we describe an approach to the clinical management of patients with insufficient inhibition of ADP dependent platelet aggregation by clopidogrel involving dose adjustment or switching of the thienoyridine. We put special emphasize on a patient who experienced recurrent acute myocardial infarction due to stent thrombosis associated with severe clopidogrel non response following elective coronary drug eluting stent implantation. In this patient, an inadequate clopidogrel effect at maintenance doses was confirmed by repeated platelet function assessment with a multiple electrode impedance point of care platelet function test. Subsequent dose adjustments still did not result in sufficient inhibition of ADP dependent platelet aggregation. Only after switching to the then shortly available new thienopyridine prasugrel could a sufficient platelet inhibition be obtained. However, our data from further patients show that although this may overcome inadequate clopidogrel efficiency in many cases, even under prasugrel suboptimal platelet inhibition may occur.

Observation of negative absolute resistance in a Josephson junction.

We experimentally demonstrate the occurrence of negative absolute resistance (NAR) up to about -1 Omega in response to an externally applied dc current for a shunted Nb-Al/AlO_{x}-Nb Josephson junction, exposed to a microwave current at frequencies in the GHz range. The realization (or not) of NAR depends crucially on the amplitude of the applied microwave current. Theoretically, the system is described by means of the resistively and capacitively shunted junction model in terms of a moderately damped, classical Brownian particle dynamics in a one-dimensional potential. We find excellent agreement of the experimental results with numerical simulations of the model.