ObjectiveTo investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.MethodsPrevious systematic literature reviews performed by EULAR... Show moreObjectiveTo investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.MethodsPrevious systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF+ vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses.ResultsData from 28 eligible RCTs were analysed, pooling 23 studies in three subgroups: six including csDMARD-naive patients, 14 csDMARD-IR and three TNFi-IR patients. In csDMARD-naive and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88–1.18) and 1.09 (0.90–1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on three trials, the 6-month ACR20 RRR was 2.28 (1.31–3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs.ConclusionThe effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used. Show less
Hypothesis: Insertion speed during cochlear implantation determines the risk of cochlear trauma. By slowing down insertion speed tactile feedback is improved. This is highly conducive to control... Show moreHypothesis: Insertion speed during cochlear implantation determines the risk of cochlear trauma. By slowing down insertion speed tactile feedback is improved. This is highly conducive to control the course of the electrode array along the cochlear contour and prevent translocation from the scala tympani to the scala vestibuli. Background: Limiting insertion trauma is a dedicated goal in cochlear implantation to maintain the most favorable situation for electrical stimulation of the remaining stimulable neural components of the cochlea. Surgical technique is one of the potential influencers on translocation behavior of the electrode array. Methods: The intrascalar position of 226 patients, all implanted with a precurved electrode array, aiming a mid-scalar position, was evaluated. One group (n = 113) represented implantation with an insertion time less than 25 seconds (fast insertion) and the other group (n = 113) was implanted in 25 or more seconds (slow insertion). A logistic regression analysis studied the effect of insertion speed on insertion trauma, controlled for surgical approach, cochlear size, and angular insertion depth. Furthermore, the effect of translocation on speech performance was evaluated using a linear mixed model. Results: The translocation rate within the fast and slow insertion groups were respectively 27 and 10%. A logistic regression analysis showed that the odds of dislocation increases by 2.527 times with a fast insertion, controlled for surgical approach, cochlear size, and angular insertion depth (95% CI = 1.135, 5.625). We failed to find a difference in speech recognition between patients with and without translocated electrode arrays. Conclusion: Slowing down insertion speed till 25 seconds or longer reduces the incidence of translocation. Show less
Objectives To transfer sterile medical devices (SMD), infusion bags (IB), ampoules (A), injection vials (V) and infusion bottles (B) into a laminar airflow cabinet (LAF) or safety cabinet (SC) with... Show moreObjectives To transfer sterile medical devices (SMD), infusion bags (IB), ampoules (A), injection vials (V) and infusion bottles (B) into a laminar airflow cabinet (LAF) or safety cabinet (SC) with a surface bioburden as low as possible. Methods Surface bioburden of the outer layer of SMD, IB, A, V and B was determined by contact plates. Surface bioburden determination of critical spots on A, V and B (ampoule necks and stoppers) was determined by high-recovery swabs and contact plates. Particle emission from white cardboard boxes was determined by a particle counter. Results The chances of a contaminated outer layer of SMD is negligible as long as they stay in their original boxes. The outer layer of double-packed IB can contain a considerable number of micro-organisms. As found in previous studies, the surface bioburden of A, V and B is low as long as they stay in their original cardboard boxes. Particle emission from white boxes is low. The necessity of a final disinfection step inside LAF/SC of critical sspots of A, V and B cannot be proven. SmallSMD, ampoules and injection vials can be transferred into the background areain their original white boxes. Other materials have to be unpacked in front ofthe lock while the operator wear disposable gloves. Disinfection of the outerlayer of IB, before transfer trough the lock, is advised. Tohave materials with a low chance of contamination in LAF/SC, transfer bypresentation for SMD and IB and using a sterile tray for disinfected materialsis an effective procedure. Wiping of ampoule necks and stoppers inside LAF/SC isadvised based on risk assessment. Small SMD, ampoules and injection vials can be transferred into the background areain their original white boxes. Other materials have to be unpacked in front ofthe lock while the operator wear disposable gloves. Disinfection of the outerlayer of IB, before transfer trough the lock, is advised. Conclusion When SMD, ampoules, injection vials and infusion bottles stay in their original boxes as long as possible, the aseptic transfer and the disinfection procedure can be maintained effectively and efficiently. Show less
Background: Preterm infants are commonly supported with 5-8 cmH(2)O CPAP. However, animal studies demonstrate that high initial CPAP levels (12-15 cmH(2)O) which are then reduced (termed... Show moreBackground: Preterm infants are commonly supported with 5-8 cmH(2)O CPAP. However, animal studies demonstrate that high initial CPAP levels (12-15 cmH(2)O) which are then reduced (termed physiological based (PB)-CPAP), improve lung aeration without adversely affecting cardiovascular function. We investigated the feasibility of PB-CPAP and the effect in preterm infants at birth.Methods: Preterm infants (24-30 weeks gestation) were randomized to PB-CPAP or 5-8 cmH(2)O CPAP for the first 10 min after birth. PB-CPAP consisted of 15 cmH(2)O CPAP that was decreased when infants were stabilized (heart rate >= 100 bpm, SpO(2) >= 85%, FiO(2) <= 0.4, spontaneous breathing) to 8 cmH(2)O with steps of ~2/3 cmH(2)O/min. Primary outcomes were feasibility and SpO(2) in the first 5 min after birth. Secondary outcomes included physiological and breathing parameters and short-term neonatal outcomes. Planned enrollment was 42 infants.Results: The trial was stopped after enrolling 31 infants due to a low inclusion rate and recent changes in the local resuscitation guideline that conflict with the study protocol. Measurements were available for analysis in 28 infants (PB-CPAP n = 8, 5-8 cmH(2)O n = 20). Protocol deviations in the PB-CPAP group included one infant receiving 3 inflations with 15 cmH(2)O PEEP and two infants in which CPAP levels were decreased faster than described in the study protocol. In the 5-8 cmH(2)O CPAP group, three infants received 4, 10, and 12 cmH(2)O CPAP. During evaluations, caregivers indicated that the current PB-CPAP protocol was difficult to execute. The SpO(2) in the first 5 min after birth was not different [61 (49-70) vs. 64 (47-74), p = 0.973]. However, infants receiving PB-CPAP achieved higher heart rates [121 (111-130) vs. 97 (82-119) bpm, p = 0.016] and duration of mask ventilation was shorter [0:42 (0:34-2:22) vs. 2:58 (1:36-6:03) min, p = 0.020]. Infants in the PB-CPAP group required 6:36 (5:49-11:03) min to stabilize, compared to 9:57 (6:58-15:06) min in the 5-8 cmH2O CPAP group (p = 0.256). There were no differences in short-term outcomes.Conclusion: Stabilization of preterm infants with PB-CPAP is feasible but tailoring CPAP appeared challenging. PB-CPAP did not lead to higher SpO(2) but increased heart rate and shortened the duration of mask ventilation, which may reflect faster lung aeration. Show less
Objectives To improve the disinfection methods for materials with a non-sterile surface to be used in aseptic handling. Methods The surface bioburden on ampoules (A) and injection vials (IV) is... Show moreObjectives To improve the disinfection methods for materials with a non-sterile surface to be used in aseptic handling. Methods The surface bioburden on ampoules (A) and injection vials (IV) is determined by contact plates and total immersion. The occurrence of spore-forming bacteria is determined by strain colouring and matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The disinfection procedures of non-sterile materials in 10 hospital pharmacies are judged by observing. Results After wiping according to local disinfection methods, the mean surface bioburden determined by contact plates in 10 hospital pharmacies is 0.36 (plastic A), 0.50 (glass A) and 0.29 colony-forming unit (cfu) (IV). The observers found great differences in accuracy of wiping and degree of wetting the sterile gauzes. After improved wiping with commercially available alcohol impregnated sterile wipes and a two-towel technique (one-step TT disinfection), the mean surface bioburden determined by contact plates is 0.03 (plastic A), 0.2 (glass A) and 0.13 cfu (IV). Further improvement can be reached by submerging A and IV in ethanol 70% followed by improved wiping (two-step TT disinfection), but still micro-organisms will remain (mean surface bioburden determined by total immersion is 0 (plastic A) and 0.3 cfu (IV); glass A not determined). Two-step TT disinfection is more labour intensive. Spilling of alcohol is another disadvantage. However, we presume one-step TT disinfection is effective enough in daily practice. Routine surface bioburden determinations have to prove this. The effectiveness of the combination of spray and wipe is not examined because we observed a quick disappearance of alcohols from vertical as well as horizontal surfaces, which shortens the contact time to far below the advised 2 min. Spore-forming bacteria disappear as quickly as other micro-organisms during disinfection by alcohols. Conclusion Local disinfection procedures can be improved. Complete removal of micro-organisms from materials with a non-sterile surface, even after two-step TT disinfection, is impossible. Routine surface bioburden determinations have to prove if one-step TT disinfection is effective enough. Show less
ObjectivesTo develop methods for surface bioburden determination of ampoules and vials to be used in the validation of the disinfection procedures and in routine monitoring of ampoules and vials... Show moreObjectivesTo develop methods for surface bioburden determination of ampoules and vials to be used in the validation of the disinfection procedures and in routine monitoring of ampoules and vials.MethodsThe surface bioburdens of ampoules and vials are determined before and after disinfection by contact plates and total immersion.ResultsThe mean surface bioburdens of non-disinfected ampoules and vials taken straight from the original boxes are 2.4 and 5.01 cfu (total immersion; n = 20), and 0.97 and 0.94 cfu (contact plates; n = 60). The mean surface bioburdens of ampules and vials after disinfection by wiping are 1.15 and 7.50 cfu (total immersion; n = 20), and 0.12 and 0.10 cfu (contact plates; n = 60). The high number of cfu on vials (total immersion) indicate hidden cfu around the neck not removable by wiping and not detected by contact plates. Total immersion needs special laboratory facilities and is expensive (about euro50 a sample). Therefore, it is less appropriate for use in routine monitoring. However, because of the high recovery, it is the method of choice for the validation of the disinfection procedure. Surface bioburden determination by contact plates is relatively simple. Non-flat surfaces cannot be reached, but the recovery from the touched flat part of the surface is high (around 50%). The recovery from swabs is low (around 10%). Another disadvantage of swabs is the laboratory work after sampling. We therefore advise contact plates for routine monitoring. To get a reliable value of the mean surface bioburden at least 30 samples need to be examined.ConclusionTotal immersion is the method of choice for the determination of the effectiveness of a disinfection procedure for ampoules and vials. Contact plate is the method of choice for routine monitoring of the surfaces of ampoules and vials. Show less
Objective: To test the channel discrimination of cochlear implant (CI) users along all contacts of the electrode array and assess whether this is related to speech perception.Design: CI recipients... Show moreObjective: To test the channel discrimination of cochlear implant (CI) users along all contacts of the electrode array and assess whether this is related to speech perception.Design: CI recipients were tested with a custom-made channel discrimination test. They were asked to distinguish a target stimulus from two reference stimuli in a three-alternative forced choice (3AFC) task. The target stimulus was evoked using current steering, with current steering coefficients () of 1, 0.5 and 0.25. The test provided a discrimination score (D) for each electrode contact along the array.Study sample: Thirty adults implanted with a CI from Advanced Bionics.Results: Large variations in D scores were observed, both across the electrode array and between subjects. Statistical analysis revealed a significant channel-to-channel variability in D score (p<0.01). Further, there was a significant relationship between subjects' D scores and their speech perception in quiet (p<0.001).Conclusions: The large variations in D score emphasise the importance of testing pitch discrimination across the complete electrode array. The relationship between D score and speech perception indicates that pitch discrimination might be a contributing factor to the performance of individual implant users. Show less
Muller, P.H.; Brinkman, D.M.C.; Schonenberg-Meinema, D.; Bosch, W.B. van den; Koopman-Keemink, Y.; Brederije, I.C.J.; ... ; Cate, R. ten 2019
It is hypothesized that certain alleles can have a protective effect not only when inherited by the offspring but also as noninherited maternal antigens (NIMA). To estimate the NIMA effect, large... Show moreIt is hypothesized that certain alleles can have a protective effect not only when inherited by the offspring but also as noninherited maternal antigens (NIMA). To estimate the NIMA effect, large samples of families are needed. When large samples are not available, we propose a combined approach to estimate the NIMA effect from ascertained nuclear families and twin pairs. We develop a likelihood-based approach allowing for several ascertainment schemes, to accommodate for the outcome-dependent sampling scheme, and a family-specific random term, to take into account the correlation between family members. We estimate the parameters using maximum likelihood based on the combined joint likelihood (CJL) approach. Simulations show that the CJL is more efficient for estimating the NIMA odds ratios as compared to a families-only approach. To illustrate our approach, we used data from a family and a twin study from the United Kingdom on rheumatoid arthritis, and confirmed the protective NIMA effect, with an odds ratio of 0.477 (95% CI 0.264-0.864). Show less
Boehringer, S.; Guenther, M.; Sinigerova, S.; Wurtz, R.P.; Horsthemke, B.; Wieczorek, D. 2011
