[Medication verification in hospital: is it proportional?] / Medicatieverificatie in ziekenhuizen: een proportioneel instrument?

In 2008 in the Netherlands the Guideline 'Transmission of medication in the chain' was published. This guideline described that upon admission and discharge in the hospital verification of medication should take place. This caused significant investments in staff by hospitals to meet with this guideline. However, despite these efforts 15 years later this has not led to adequate transmission of medication. In this article it is described that the organization of medication verification in hospitals has features of the Risk Regulation Reflex. A better possible solution of this problem is proposed: making community pharmacies responsible for updating the medication overview. This pharmacist should perform this task together with the patient. This should be done in parallel with improving compliance. In hospitals medication reviews in high risk patients could take place.

Causal inference using observational intensive care unit data: a scoping review and recommendations for future practice.

This scoping review focuses on the essential role of models for causal inference in shaping actionable artificial intelligence (AI) designed to aid clinicians in decision-making. The objective was to identify and evaluate the reporting quality of studies introducing models for causal inference in intensive care units (ICUs), and to provide recommendations to improve the future landscape of research practices in this domain. To achieve this, we searched various databases including Embase, MEDLINE ALL, Web of Science Core Collection, Google Scholar, medRxiv, bioRxiv, arXiv, and the ACM Digital Library. Studies involving models for causal inference addressing time-varying treatments in the adult ICU were reviewed. Data extraction encompassed the study settings and methodologies applied. Furthermore, we assessed reporting quality of target trial components (i.e., eligibility criteria, treatment strategies, follow-up period, outcome, and analysis plan) and main causal assumptions (i.e., conditional exchangeability, positivity, and consistency). Among the 2184 titles screened, 79 studies met the inclusion criteria. The methodologies used were G methods (61%) and reinforcement learning methods (39%). Studies considered both static (51%) and dynamic treatment regimes (49%). Only 30 (38%) of the studies reported all five target trial components, and only seven (9%) studies mentioned all three causal assumptions. To achieve actionable AI in the ICU, we advocate careful consideration of the causal question of interest, describing this research question as a target trial emulation, usage of appropriate causal inference methods, and acknowledgement (and examination of potential violations of) the causal assumptions.

Lung ultrasound to predict gas-exchange response to prone positioning in COVID-19 patients: A prospective study in pilot and confirmation cohorts.

PURPOSE: To examine whether lung ultrasound prior to prone positioning can predict the resulting gas-exchange response. MATERIALS AND METHODS: This is a prospective observational study on critically-ill COVID-19 patients with a pilot and confirmation cohort. Lung ultrasound examinations were performed before prone positioning and gas-exchange parameters were recorded before and after position change. RESULTS: A total of 79 patients, 36 in the pilot cohort and 43 in the confirmation cohort, were included. In the pilot cohort, a moderate correlation between pre-turn lung ultrasound score index (LUSI) and change in PaO2/FiO2 after prone positioning was found. These findings were corroborated and extended upon in the confirmation cohort. The confirmation cohort found that anterior LUSI had the strongest correlation with follow-up time-points 1, 6, 12, and 24 h after prone positioning, with strength of correlation gradually increasing up to 24 h. In a multivariate model anterior aeration loss (odds ratio 0.035; 95%CI 0.003-0.319 for anterior LUSI >50%) and higher pre-turn PaCO2 (odds ratio 0.479 95% CI 0.235-0.979) were negatively predictive of a PaO2/FiO2 increase ≥20 mmHg. CONCLUSIONS: Anterior LUSI, in addition to other clinical parameters, may be used to aid COVID-19 respiratory strategy and a clinician's decision to prone.

The Zwolle experience with left bundle branch area pacing using stylet-driven active fixation leads.

AIMS: Left bundle branch area pacing (LBBAP) is a novel physiological pacing modality and is regarded as a viable alternative to His bundle pacing. LBBAP has mostly been performed with the lumen-less permanent pacing lead (SelectSecure™ Model 3830, Medtronic, Inc.) with a fixed helix. The aim of this study was to compare the non-stylet driven lumen-less lead (LLL) (Medtronic 3830) with a standard stylet-driven active fixation lead (SDL) (Tendril™ STS Model 2088TC-38, Abbott Laboratories) in terms of lead parameters, procedural success and complication rates. METHODS: Patients receiving a LBBA pacemaker in the Isala Hospital, The Netherlands, were prospectively enrolled. The majority received a standard right ventricular (RV) lead as backup, the implanter chose between LLL and SDL for the LBBAP lead. RESULTS: The study included 94 patients with a mean follow-up of 30 weeks. 30/31 LLL procedures were successful, compared with 62/63 in the SDL group. Including the participants that lost LBBAP during follow-up resulted in success rates of 90.3% for LLL versus 96.8% for SDL, P = 0.199. Mean number of deployments was significantly lower in the SDL group compared with the LLL group (2 ± 2.3 versus 4 ± 3.4, P = 0.005), implantation and procedural times were comparable. Pacing thresholds were low and remained low in both groups (at last follow-up 0.8 ± 0.30 V for LLL versus 0.6 ± 0.20 V for SDL). Complication rates did not differ significantly between both groups, P = 0.805. CONCLUSION: LBBAP using SDL is feasible and has comparable success rates with lower number of deployments of the active fixation screw.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients - A diagnostic accuracy study.

PURPOSE: Critically ill COVID-19 patients have an increased risk of developing pulmonary embolism (PE). Diagnosis of PE by point-of-care ultrasound (POCUS) might reduce the need for computed tomography pulmonary angiography (CTPA), while decreasing time-to-diagnosis. MATERIALS & METHODS: This prospective, observational study included adult ICU patients with COVID-19. Multi-organ (lungs, deep vein, cardiac) POCUS was performed within 24 h of CTPA, looking for subpleural consolidations, deep venous thrombosis (DVT), and right ventricular strain (RVS). We reported the scan time, and calculated diagnostic accuracy measures for these signs separately and in combination. RESULTS: 70 consecutive patients were included. 23 patients (32.8%) had a PE. Median scan time was 14 min (IQR 11-17). Subpleural consolidations' diagnostic accuracy was: 42.9% (95%CI [34.1-52.0]). DVT's and RVS' diagnostic accuracy was: 75.6% (95%CI [67.1-82.9]) and 74.4% (95%CI [65.8-81.8]). Their sensitivity was: 24.0% (95%CI [9.4-45.1]), and 40.0% (95%CI [21.3-61.3]), while their specificity was: 88.8% (95%CI [80.8-94.3]), and: 83.0% (95%CI [74.2-89.8]), respectively. Multi-organ POCUS sensitivity was: 87.5% (95%CI [67.6-97.3]), and specificity was: 25% (95%CI [16.9-34.7]). CONCLUSIONS: Multi-organ rather than single-organ POCUS can be of aid in ruling out PE in critically ill COVID-19 and help select patients for CTPA. In addition, finding RVS can make PE more likely, while a DVT would preclude the need for a CTPA. REGISTRATION: www.trialregister.nl: NL8540.

Long-Term Changes in Free Nipple Graft Morphology and Patient-Reported Outcomes in Gender-Affirming Mastectomies.

BACKGROUND: After gender-affirming mastectomies with free nipple grafts, satisfaction with nipples tends to fall short behind chest outcomes. This might be related to changes in nipple areolar complex (NAC) dimensions over time. Therefore, the aim of this study is to establish the long-term changes in NAC morphology and compare these to cisgender male NAC outcomes. MATERIALS: An observational, cross-sectional study was performed. Data from two prospective cohorts were collected: (1) transgender men after a mastectomy with free nipple grafts and (2) cisgender men (reference sample). Demographics and 3-D images were collected for both groups. NAC measurements were performed on the 3-D images at 4 time points (7-, 30-, 90- and 365-days postoperative) in transgender men and once in cisgender men. Furthermore, the BODY-Q (nipple module) was administered postoperatively at 30-, 90- and 365-days in transgender men. RESULTS: In total, 67 transgender and 150 cisgender men were included. NAC width and height in trans men changed from 21.5 mm (±2.7) to 23.8 mm (±3.9, p<0.001) and 16.2 mm (±2.5) to 14.7 mm (±3.0, p=0.01) within a year, respectively. On average, the NACs increasingly rotated 21 degrees in the latero-caudal direction (p<0.001). The mean NAC width and height in cisgender men were 28.1 mm (±5) and 20.7 mm (±4), being significantly larger than in transgender men. Satisfaction for size, shape and flatness decreased significantly after postoperative day 30 (p=<0.05) in transgender men. CONCLUSIONS: Morphology of and satisfaction with the NACs in transgender men significantly changed over time. Understanding and incorporating these differences into pre-operative counseling and surgical planning might help increase patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Within-patient randomized clinical trial comparing incisional negative-pressure wound therapy with suction drains in gender-affirming mastectomies.

BACKGROUND: Incisional negative-pressure wound therapy (iNPWT) is widely adopted by different disciplines for multiple indications. Questions about the most appropriate uses and value of iNPWT have been raised. METHODS: An open-label within-patient RCT was conducted in transgender men undergoing gender-affirming mastectomies. The objective was to determine the effect of iNPWT as a substitute for standard dressing and suction drains on wound healing complications. One chest side was randomized to receive the iNPWT intervention, and the other to standard dressing with suction drain. The primary endpoints were wound healing complications (haematoma, seroma, infection, and dehiscence) after three months. Additional outcomes were pain according to a numerical rating scale and patient satisfaction one week after surgery. RESULTS: Eighty-five patients were included, of whom 81 received both the iNPWT and standard treatment. Drain removal criteria were met within 24 h in 95 per cent of the patients. No significant decrease in wound healing complications was registered on the iNPWT side, but the seroma rate was significantly increased. In contrast, patients experienced both significantly less pain and increased comfort on the iNPWT side. No medical device-related adverse events were registered. CONCLUSION: Substituting short-term suction drains with iNPWT in gender-affirming mastectomies increased the seroma rates and did not decrease the amount of wound healing complications. Registration number: NTR7412 (Netherlands Trial Register).

[Involving forensic psychiatric patients in scientific research]. / De bereidheid van forensisch psychia­trische patiënten tot deelname aan wetenschappelijk onderzoek.

Background Forensic psychiatric patients are at risk to cause damage to society in the future again, both materially and immaterially. Little is known about the pharmacotherapeutic or psychotherapeutic treatment of the specific psychopathology of forensic psychiatric patients. This is possibly due to scarcity of research in the field, which could be caused by the fact that forensic psychiatric patients are often unwilling to participate in scientific research. Aim To explore the reasons why patients are unwilling to participate in research. Method Sixty-five forensic psychiatric patients were asked about their opinion on participating in pharmacological, psychotherapy, MRI- and DNA research.  Results The main reasons for not participating in pharmacological research were 'patient's belief that they will not benefit from participation in research' and 'physical integrity' (the fear of being physically harmed by participation in research). 'General resistance' (not willing to take part for no particular reason) was the main reason for not participating in psychotherapy-, MRI and DNA research.  Conclusion In order to enhance willingness to take part in research, informing the patients in the right manner with the aim of taking distrust away, would be important. Also, it could be helpful to offer a reward for participation in scientific research, although this could lead to ethical complications.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Phagocytosis and macrophage polarization on bacterially contaminated dental implant materials and effects on tissue integration.

Bacterial contamination is hard to avoid during dental implant surgery. Macrophages and their polarisation play a decisive role in bacterial colonisation and tissue integration on bacterially contaminated dental implants. The present study investigated the role of macrophages in stimulating tissue coverage overgrowth of contaminating oral bacteria on polished titanium (Ti-P) and acid-etched zirconium dioxide (ZrO2-MA) dental implant materials. Different co-culture models were employed to determine phagocytosis rates of Streptococcus mitis or Staphylococcus aureus contaminating a dental implant surface and the influence of contaminating bacteria and osteoblasts (U2OS) on macrophage polarisation. S. aureus was phagocytized in higher numbers than S. mitis in bi-cultures on smooth Ti-P surfaces. Contaminating S. mitis stimulated near full polarisation of macrophages from a non-Ym1-expressing- to a Ym1-expressing-phenotype on smooth Ti-P, but on ZrO2-MA both phenotypes occurred. In tri-cultures with U2OS-cells on smooth Ti-P, a larger percentage of macrophages remained in their non-Ym1-expressing, "fighting" M1-like phenotype to clear Ti-P surfaces from contaminating bacteria. On ZrO2-MA surfaces, more macrophages tended towards their "fix- and-repair" M2-like phenotype than on Ti-P surfaces. Surface coverage of smooth, bacterially contaminated Ti-P surfaces by U2OS-cells was more effectively stimulated by fighting, M1-like macrophages than on ZrO2-MA surfaces. Comprehensive guidelines are provided for the development of infection-resistant, dental implant materials, including bacteria, tissue and immune cells. These guidelines point to more promising results for clinical application of Ti-P as compared with ZrO2-MA.

Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

[Black particles in plasma and carcinogenic pills]. / Zwarte deeltjes in plasma en kankerverwekkende pillen.

Recently in a national newspaper presumed large hazards in care were described. Visible black particles were seen in blood plasma and a cancerogenic substance was found in paracetamol. Every year 300.000 bags of plasma are produced. The black particles were found in 11 bags of plasma. Possibly one of these was administered. During administration 175 micron filters are used. Presumably remaining particles will be degraded by the mononuclear-phagocytic system. In paracetamol 6 ppm of para-chloroaniline was found. Depending of the limit used by either the ICH or the EFSA this means for patients using lifelong 6 grams of paracetamol a risk off respectively 1: 200.000 or 1:20.000. This risk is neglectable compared of the life time risks of cancer in the population (1:3). Journalists should realize that this exaggerated commentary can lead to real serious risks (taking NSAID's instead of paracetamol) and mistrust in regular care.

Human papillomavirus and cervical cancer risk perception and vaccine acceptability among adolescent girls and young women in Durban, South Africa.

BACKGROUND: The relationship between HIV and cervical cancer is well established. Interventions that focus on creating human papillomavirus (HPV) vaccine and cervical cancer prevention messaging for adolescents, caregivers and educators will increase uptake of HPV vaccinations, HPV testing and cervical cancer screening for high-risk adolescent girls and young women (AGYW). In order to effectively develop appropriate interventions, it is important to examine AGYW's perceptions regarding their personal risk of acquiring HPV, as well as vaccine acceptability. OBJECTIVES: To measure the level of perceived personal risk of acquiring HPV and developing cervical cancer; examine the sociodemographic and behavioural factors associated with perceived risk; and assess HPV vaccine acceptability. METHODS: AGYW aged 16 - 24 years participating in the AYAZAZI study in Durban, South Africa (SA), were invited to participate in the AYA-HPV Prevention Project (AHPP), and were administered a questionnaire that assessed HPV, cervical cancer and vaccine awareness and knowledge, self-perceived HPV and cervical cancer risk, HPV vaccine uptake and acceptability, and participation in cervical cancer screening. The questionnaire measured self-perceived risk of acquiring HPV and developing cervical cancer for the respondent and other young women, as well as vaccine acceptability. Data from the main AYAZAZI study (12-month) visit were linked to AHPP substudy data. Descriptive statistics were used to analyse sociodemographic variables at the 12-month time point. Self-perceived HIV, HPV and cervical cancer risk was measured using an ordinal scale. Chi-square analyses were used to examine differences in sociodemographic and behavioural factors according to self-perceived risk of HPV and cervical cancer. RESULTS: Only a small portion of participants (14.3%) had heard of HPV. Overall, 43.0% (n=49) perceived themselves as at low HPV risk. There were significant differences in self-perceived risk of cervical cancer by age group, income and pregnancy status. The highest proportion of AGYW who perceived themselves as at high risk of cervical cancer reported being sexually active (p=0.002). Although many participants reported not knowing about HPV prior to the study, after learning about it during the study, most said that they would be willing to receive the vaccine (97.5%). CONCLUSIONS: Most young women in SA do not have access to the national HPV vaccine programme, as only girls in grade 4 in some public schools qualify. Almost all participants indicated that if the vaccine was free and recommended by a healthcare professional, they would accept it. Availability of the HPV vaccine and timely treatment of HPV infections are key issues to address in efforts to decrease cervical cancer worldwide.

Ever and repeat HIV testing rates among male and female clients: Findings from a reproductive health services integration project in South Africa.

BACKGROUND: HIV testing rates have increased in recent years. Repeat testing is recommended to identify and treat new HIV infections timeously. However, there are limited data on repeat HIV testing, especially in South Africa (SA). OBJECTIVES: To provide data on repeat HIV testing rates in males and females in a district in SA. METHODS: A sexual and reproductive health (SRH) service integration model was implemented in seven healthcare facilities in eThekwini District, KwaZulu-Natal Province, SA, between 2009 and 2011. HIV testing data were collected from male and female clients attending these facilities, prior to (baseline) and after the implementation (endline) of the 3-year health services integration intervention. RESULTS: There were 230 clients at baseline (195 female, 35 male) and 200 at endline (169 female, 31 male). High ever-tested rates were reported at baseline (females 95.4%, males 74.3%) and endline (females 91.7%, males 87.1%), with large increases in male testing rates over time. In addition, high increases were seen between baseline and endline among those who had tested more than once and more than twice in their lifetime. Increases between baseline and endline testing rates were highest in HIV testing services (HTS) (37.0 - 93.3% for clients who had tested more than once, and 11.1 - 53.3% for those who had tested more than twice). CONCLUSIONS: HIV testing and repeat testing increased over time, especially in males and in HTS. Promotion and integration of SRH services are critical to facilitate improved health-seeking behaviour and HIV testing of both male and female clients. They are also important for continued access to HTS at multiple service delivery points.

The outcome of pulmonary hypertension and its association with pulmonary artery dilatation.

BACKGROUND: Pulmonary artery (PA) dilatation is often seen in pulmonary hypertension (PH) and is considered a long-term consequence of elevated pressure. The PA dilates over time and therefore may reflect disease severity and duration. Survival is related to the stage of the disease at the time of diagnosis and therefore PA diameter might be used to predict prognosis. This study evaluates the outcome of patients with pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) and investigates whether PA diameter at the time of diagnosis is associated with mortality. METHODS: Patients visiting an outpatient clinic of a tertiary centre between 2004 and 2018 with a cardiac catheterisation confirmed diagnosis of PAH or CTEPH and a CT scan available for PA diameter measurement were included. PA diameter and established predictors of survival were collected (New York Heart Association (NYHA) class, N­terminal pro-brain natriuretic peptide (NT-proBNP) level and 6­min walking distance (6MWD)). RESULTS: In total 217 patients were included (69% female, 71% NYHA class ≥III). During a median follow-up of 50 (22-92) months, 54% of the patients died. Overall survival was 87% at 1 year, 70% at 3 years and 58% at 5 years. The mean PA diameter was 34.2 ± 6.2 mm and was not significantly different among all the diagnosis groups. We found a weak correlation between PA diameter and mean PA pressure ( r = 0.23, p < 0.001). Male sex, higher age, shorter 6MWD and higher NT-proBNP level were independently associated with mortality, but PA diameter was not. CONCLUSION: The prognosis of PAH and CTEPH is still poor. Known predictors of survival were confirmed, but PA diameter at diagnosis was not associated with survival in PAH or CTEPH patients.

A multi-center assessment to compare residual allergenicity of partial hydrolyzed whey proteins in a murine model for cow's milk allergy - Comparison to the single parameter guinea pig model.

INTRODUCTION: This 4-center study is part of a project to validate a food allergy murine model for safety testing of hydrolyzed infant formulas. AIM: The aim of the current multi-center experiment was to evaluate the residual allergenicity of three partial hydrolyzed whey proteins (pWH) in a multiple-parameter cow's milk allergy murine model and to compare to the classically used guinea pig model. Previous work showed differences in the magnitude of the allergic response to whey between centers. To get a first insight in the effect of housing on the robustness of the mouse model, microbiota composition of non-sensitized mice was analyzed and compared between centers. METHODS: Mice were sensitized intragastrically (i.g.) with whey, pWH or eWH using cholera toxin as an adjuvant. In mice, whey-IgE/IgG1, acute allergic symptoms were determined upon whey challenge. Guinea pigs were orally sensitized ad libitum via the drinking water (day 0-37) and challenged intravenously with whey on day 49. The microbial composition in fecal samples was determined in non-sensitized mice in all 4 research centers before and after conduct of the study. RESULTS: Elevated levels of whey-IgG1 were detected in whey-sensitized mice in all centers. Except for pWH-A in center 4, we observed elevated levels of whey-IgE in whey-sensitized mice and mice sensitized with pWH-A, -B, -C. Center 2 was excluded from further analysis because of non-significant IgE levels in the positive control. In contrast to whey-mice, pWH-A treated mice showed no acute skin response, mMCP-1 release or change in body temperature upon whey challenge in all centers, which corresponds with the absence of anaphylactic shock symptoms in both the mouse and guinea pig model. pWH-B and -C induced anaphylactic shock symptoms in the guinea-pig and mice whereas results on the remaining allergic outcomes in mice were inconclusive. No differences in microbiota composition were measured in response to the challenge and Microbiota composition depended on the location of the centers. CONCLUSIONS: Both animal models showed comparable results on the residual allergenicity of partial hydrolyzed whey proteins, but none of the centers was able to differentiate between the residual sensitizing capacities of the pWH-B and -C based on a single elicitation parameter in the murine model. Differences in microbiota composition might contribute to the robustness of the food allergy murine model. For a well-balanced prediction on the potential allergenicity of hydrolyzed infant formulas a multiple murine parameter model is suggested to decrease the risk of false positive or false negative results. A future challenge is to develop an overall scoring system for proper risk assessment, taking all parameters into account.