PROMISE: effect of protein supplementation on fat-free mass preservation after bariatric surgery, a randomized double-blind placebo-controlled trial.

INTRODUCTION: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS AND ANALYSIS: Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA). ETHICS AND DISSEMINATION: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022.

18F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction: Accuracy and Long-Term Implications.

PURPOSE: The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10-40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. METHODS: Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. RESULTS: Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. CONCLUSION: Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.

Burden of mental health problems: quality of life and cost-of-illness in youth consulting Dutch walk-in youth health centres.

BACKGROUND: Little is known about the burden of (sub-threshold) mental health problems in youth. AIM: To examine the burden of mental health problems in terms of health-related quality of life (HRQoL) and cost-of-illness, for first visitors of the Dutch youth walk-in centres (@ease). METHOD: A bottom-up, prevalence-based burden of disease study from a societal perspective. HRQoL was assessed through the EuroQoL (EQ-5D-5L), and cost-of-illness via items about truancy and health care utilization. RESULTS: Participants (N = 80) showed a decreased HRQoL compared to the general population of Dutch youth. In the three months prior to their 1st attendance, participants skipped on average 4.11 days of school and had 1.03 health care visits, leading to total costs of €512.64 per person. Females had significantly higher health care costs and lower HRQoL. Health care use was lower in those not speaking the Dutch language. Living alone was a significant predictor of truancy (costs), and therefore total costs. CONCLUSIONS: Mental health problems in youth consulting @ease have a considerable impact on the individual's HRQoL, and an economic impact on society, yet almost 75% is not receiving care. A lack of interventions in this critical period in life may have major lifelong consequences.

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery.

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.

Resizing a large pouch after laparoscopic Roux-en-Y gastric bypass: comparing the effect of two techniques on weight loss.

BACKGROUND: Insufficient weight loss or weight regain has many causes including a large gastric pouch. A large gastric pouch may be due to the surgical technique or can be patient related (dilation). Resizing the gastric pouch may lead to additional weight loss. Currently, there is no gold standard for the revisional surgical technique. Therefore this study was performed to determine which surgical technique for revisional bariatric surgery (BS) has superior outcomes in terms of weight loss: sleeve resection of the gastrojejunostomy and gastric pouch (SGP), or resection of the gastrojejunostomy with resizing of the pouch and creation of a new anastomosis (RGJ). METHODS: All patients who underwent revisional BS for insufficient weight loss or weight regain as a result of an enlarged pouch after LRYGB from April 2014 to June 2018 in our hospitals were included in this observational cohort study. Outcomes were measured in percentage total weight loss (%TWL). RESULTS: A total of 37 patients who underwent SGP and 21 patients who underwent RGJ as revisional BS were included in this study. The median body mass index before revisional BS was 37.6 kg/m2 versus 35.7 kg/m2 (SGP vs RGJ, respectively, P = 0.115). There was no significant difference in %TWL between the two cohorts 1 and 2 years after revisional BS, respectively; SGP 14.5% vs RGJ 11.0%, P = 0.885 and SGP 12.3% vs RGJ 10.8%, P = 0.604. Comparing %TWL based on weight at LRYGB, there was also no significant difference two years after revisional BS (SGP 22.0% vs RGJ 22.2%, P = 0.885). The average use of surgical disposables for the SGP technique were lower compared to the RGJ technique. CONCLUSIONS: Resizing a large pouch leads to additional weight loss. Both techniques have comparable outcomes in terms of weight loss. However, based on average surgical costs, the SGP technique may be preferable.

Evaluation of non-invasive imaging parameters in coronary microvascular disease: a systematic review.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD. METHODS: Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2. RESULTS: Thirty-seven studies were included. Ten cardiac magnetic resonance studies reported MPRI and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 2.01 ± 0.41 in patients and from 1.50 ± 0.47 to 2.68 ± 0.49 in controls without CMD. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively. CONCLUSIONS: This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. In current clinical practice, CMD is generally diagnosed with a CFR less than 2.0. However, due to heterogeneity in methodology and reporting of outcome measures, outcomes could not be compared and no definite reference values could be provided.

[Influence of extreme weather conditions on the deployment volume of emergency medical services]. / Einfluss von Wetterextrema auf Einsatzzahlen im Notarztdienst.

BACKGROUND: Due to global warming a worldwide increase in the frequency and intensity of heat waves have been forecast. In the context of the overall increasing number of emergency service calls, weather-induced effects on the number of calls are highly relevant. We evaluated the influence of extreme temperatures on emergency medical services. MATERIALS AND METHODS: The study was conducted in Bochum, Germany. The authors examined the data from 16,767 emergency calls. In addition, the daily updated temperature data were collected for each emergency doctor call. Data were collected from 01 January 2014 until 31 December 2015. The primary question was the influence of extremes of the perceived temperature (PT; on the day of the call and the three previous days) on the diagnosis group of cardiovascular diseases. A secondary question was the influence of extremes of the temperature parameters (air temperature, PT, physiological equivalent temperature [PET]) on the day of call and the three previous days. RESULTS: A total of 16,767 calls were assessed. The threshold values (upper and lower 5%) were -8.7 and 32.5 °C for PT and -0.7 and 26.7 °C for air temperature. Examination of the PT indicated a significantly increased rate of calls for cold spells on the day of the call (RR = 1.14; p = 0.033) as well as a lag effect of 3 days (RR = 1.1; p = 0.049). CONCLUSION: The present study shows that during cold spells there is an increased rate of calls for cardiovascular diseases. This effect is not only observable on the extreme day itself but also 3 days later.

A novel amplitude binning strategy to handle irregular breathing during 4DMRI acquisition: improved imaging for radiotherapy purposes.

BACKGROUND: For radiotherapy of abdominal cancer, four-dimensional magnetic resonance imaging (4DMRI) is desirable for tumor definition and the assessment of tumor and organ motion. However, irregular breathing gives rise to image artifacts. We developed a outlier rejection strategy resulting in a 4DMRI with reduced image artifacts in the presence of irregular breathing. METHODS: We obtained 2D T2-weighted single-shot turbo spin echo images, with an interleaved 1D navigator acquisition to obtain the respiratory signal during free breathing imaging in 2 patients and 12 healthy volunteers. Prior to binning, upper and lower inclusion thresholds were chosen such that 95% of the acquired images were included, while minimizing the distance between the thresholds (inclusion range (IR)). We compared our strategy (Min95) with three commonly applied strategies: phase binning with all images included (Phase), amplitude binning with all images included (MaxIE), and amplitude binning with the thresholds set as the mean end-inhale and mean end-exhale diaphragm positions (MeanIE). We compared 4DMRI quality based on: Data included (DI); percentage of images remaining after outlier rejection. Reconstruction completeness (RC); percentage of bin-slice combinations containing at least one image after binning. Intra-bin variation (IBV); interquartile range of the diaphragm position within the bin-slice combination, averaged over three central slices and ten respiratory bins. IR. Image smoothness (S); quantified by fitting a parabola to the diaphragm profile in a sagittal plane of the reconstructed 4DMRI. A two-sided Wilcoxon's signed-rank test was used to test for significance in differences between the Min95 strategy and the Phase, MaxIE, and MeanIE strategies. RESULTS: Based on the fourteen subjects, the Min95 binning strategy outperformed the other strategies with a mean RC of 95.5%, mean IBV of 1.6 mm, mean IR of 15.1 mm and a mean S of 0.90. The Phase strategy showed a poor mean IBV of 6.2 mm and the MaxIE strategy showed a poor mean RC of 85.6%, resulting in image artifacts (mean S of 0.76). The MeanIE strategy demonstrated a mean DI of 85.6%. CONCLUSIONS: Our Min95 reconstruction strategy resulted in a 4DMRI with less artifacts and more precise diaphragm position reconstruction compared to the other strategies. TRIAL REGISTRATION: Volunteers: protocol W15_373#16.007; patients: protocol NL47713.018.14.

Effects of bariatric surgery on telomere length and T-cell aging.

BACKGROUND: Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. METHODS: WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4+ and CD8+ T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. RESULTS: Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8+ T-cell differentiation. Patients with MetS had significant lower CD4+ RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4+ T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. CONCLUSIONS: In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

Tranexamic acid therapy for postoperative bleeding after bariatric surgery.

BACKGROUND: Tranexamic acid reduces blood loss associated with various surgical procedures. Postoperative bleeding caused by dissection or bleeding of the enteric staple lines is a well-known complication following bariatric surgery. Reoperation in order to restore hemostasis is frequently necessary (up to 2.5% in literature). The effect of conservative therapy using tranexamic acid for postoperative hemorrhage after bariatric surgery is still very much a novel technique. The aim is to present our results (reoperation rate and thrombo-embolic complication rate) of tranexamic acid therapy for postoperative bleeding after bariatric surgery in comparison to those in existing literature. METHODS: We retrospectively reviewed 1388 patients who underwent bariatric surgery (laparoscopic gastric bypass or laparoscopic gastric sleeve). Use of tranexamic acid, reoperation rate, transfusion rate and rate of thrombo-embolic complications were reviewed. RESULTS: Forty-five of 1388 (3.2%) total patients experienced significant hemorrhage after bariatric surgery. Tranexamic acid was administered in 44 of these patients. A failure of the treatment with tranexamic acid was observed in four patients. The incidence of reoperation was 0.4% for the entire population. No thrombo-embolic complications were registered for patients receiving tranexamic acid. CONCLUSION: These findings suggest that the administration of tranexamic acid appears to be safe in reducing the reoperation rate for bleeding after bariatric surgery.

Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital malformations, largely caused by mutations in various ribosomal proteins. The aim of this study was to characterize the spectrum of genetic lesions causing DBA and identify genotypes that correlate with phenotypes of clinical significance. Seventy-four patients with DBA from across Canada were included. Nucleotide-level mutations or large deletions were identified in 10 ribosomal genes in 45 cases. The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups. Patients with RPS19 mutations, however, were more likely to maintain long-term corticosteroid response without requirement for further chronic transfusions. Conversely, patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups. Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between DBA genetic groups with regards to treatment. Previously unreported differences in the rate and types of birth defects were also identified. These data allow better patient counseling, a more personalized monitoring plan, and may also suggest differential functions of DBA genes on ribosome and extra-ribosomal functions.

Treatment of extra-articular proximal and middle phalangeal fractures of the hand: a systematic review.

The aim of the study was to systematically review the patient reported and functional outcomes of treatment for extra-articular proximal or middle phalangeal fractures of the hand in order to determine the best treatment options. The review methodology was registered with PROSPERO. A systematic literature search was conducted in electronic bibliographic databases. Two independent reviewers performed screening and data extraction. The evaluation of quality of the included studies was performed using the Structured Effectiveness Quality Evaluation scale. The initial search yielded 2354 studies. The full text manuscripts of 79 studies were evaluated of which 16 studies met the inclusion criteria. In total, 513 extra-articular proximal and middle phalangeal fractures of the hand were included of which 118 (23%) were treated non-operatively, 188 (37%) were treated by closed reduction internal fixation (CRIF) and 207 (40%) by open reduction internal fixation. It can be recommended that closed displaced extra-articular phalangeal fractures can be treated non-operatively, even fractures with an oblique or complex pattern, provided that closed reduction is possible and maintained. Conservative treatment is preferably performed with a cast/brace allowing free mobilization of the wrist. No definite conclusion could be drawn upon whether closed reduction with extra-articular K-wire pinning or transarticular pinning is superior; however, it might be suggested that extra-articular K-wire pinning is favoured. When open reduction is necessary for oblique or spiral extra-articular fractures, lag screw fixation is preferable to plate and screw fixation. But, similar recovery and functional results are achieved with transversally inserted K-wires compared to lag screw fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: therapeutic III.

Generic and disease-specific quality of life among youth and young men with Hemophilia in Canada.

BACKGROUND: This study was undertaken to explore the longitudinal patterns of health-related quality of life (HRQoL) among youth and young adults with Hemophilia A (HA) over a 3-year period. This report presents the baseline characteristics of the study cohort. METHODS: Males, 14 to 29 years of age, with predominantly severe HA were recruited from six treatment centres in Canada. Subjects completed a comprehensive survey. HRQoL was measured using: the CHO-KLAT2.0 (youth), Haemo-QoL-A (young adults) and the SF-36v2 (all). RESULTS: 13 youth (mean age = 15.7, range = 12.9-17.9 years) and 33 young adults (mean age = 23.6; range = 18.4 -28.7 years) with moderate (7 %) and severe (93 %) HA were enrolled. All were on a prophylactic regimen with antihemophilic factor (Helixate FS®) during the study. The youth had minimal joint damage (mean HJHS = 5.2) compared to young adults (mean HJHS = 13.3). The mean HRQoL scores for youth were: 79.2 (SD = 11.9) for the CHO-KLAT, and 53.0 (5.5) and 52.3 (6.8) for the SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores respectively. The mean HRQoL scores for young adults were: 85.8 (9.5) for the Haemo-Qol-A, and 50.8 (6.4) and 50.9 (8.8) for PCS and MCS respectively. PCS and MCS scores were comparable to published Canadian norms, however significant differences were found for the domains of Physical Functioning and Bodily Pain. The disease-specific HRQoL scores were weakly correlated with the PCS for youth (CHO-KLAT vs. PCS r = 0.28, p = 0.35); and moderately correlated for the MCS (r = 0.39, p = 0.19). Haemo-QoL-A scores for young adults were strongly correlated with the PCS (r = 0.53, p = 0.001); and weakly correlated with the MCS (r = 0.26, p = 0.13). Joint status as assessed by HJHS was correlated with PCS scores. A history of lifelong prophylaxis resulted in better PCS but worse MCS scores. CONCLUSION: Despite having hemophilia, the youth in this cohort have minimal joint disease and good HRQoL. The young adults demonstrated more joint disease and slightly worse HRQoL in the domains of physical functioning and pain. The data presented here provide new information to inform the selection of Health Related Quality of Life (HRQoL) instruments for use in future clinical trials involving persons with hemophilia. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01034904. Study funded by CSL Behring Canada.

Development of a stage-dependent prognostic model to predict psychosis in ultra-high-risk patients seeking treatment for co-morbid psychiatric disorders.

BACKGROUND: Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders. METHOD: Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14-35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses. RESULTS: At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56-7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21-6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14-6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01-1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00-1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class. CONCLUSIONS: Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.

PCA-based groupwise image registration for quantitative MRI.

Quantitative magnetic resonance imaging (qMRI) is a technique for estimating quantitative tissue properties, such as the T1 and T2 relaxation times, apparent diffusion coefficient (ADC), and various perfusion measures. This estimation is achieved by acquiring multiple images with different acquisition parameters (or at multiple time points after injection of a contrast agent) and by fitting a qMRI signal model to the image intensities. Image registration is often necessary to compensate for misalignments due to subject motion and/or geometric distortions caused by the acquisition. However, large differences in image appearance make accurate image registration challenging. In this work, we propose a groupwise image registration method for compensating misalignment in qMRI. The groupwise formulation of the method eliminates the requirement of choosing a reference image, thus avoiding a registration bias. The method minimizes a cost function that is based on principal component analysis (PCA), exploiting the fact that intensity changes in qMRI can be described by a low-dimensional signal model, but not requiring knowledge on the specific acquisition model. The method was evaluated on 4D CT data of the lungs, and both real and synthetic images of five different qMRI applications: T1 mapping in a porcine heart, combined T1 and T2 mapping in carotid arteries, ADC mapping in the abdomen, diffusion tensor mapping in the brain, and dynamic contrast-enhanced mapping in the abdomen. Each application is based on a different acquisition model. The method is compared to a mutual information-based pairwise registration method and four other state-of-the-art groupwise registration methods. Registration accuracy is evaluated in terms of the precision of the estimated qMRI parameters, overlap of segmented structures, distance between corresponding landmarks, and smoothness of the deformation. In all qMRI applications the proposed method performed better than or equally well as competing methods, while avoiding the need to choose a reference image. It is also shown that the results of the conventional pairwise approach do depend on the choice of this reference image. We therefore conclude that our groupwise registration method with a similarity measure based on PCA is the preferred technique for compensating misalignments in qMRI.

Experience with central venous access devices (CVADs) in the Canadian hemophilia primary prophylaxis study (CHPS).

INTRODUCTION: Haemophilia A treatment with factor VIII concentrates requires frequent venipunctures; a central venous access device (CVAD) may be required to facilitate reliable venous access, especially in young children. While CVADs provide reliable venous access, complications such as infection and thrombosis may occur. AIM: The aim of this study was to assess CVAD use in the Canadian Hemophilia Primary Prophylaxis Study (CHPS), a single-arm, multi-centre prospective study whereby factor use is tailored to individual prophylactic need. METHODS: Participants received a tailored, escalating dose, prophylaxis regimen of increasing frequency of FVIII infusions: step-1: 50 IU kg(-1) once weekly; step-2: 30 IU kg(-1) twice weekly; and step-3: 25 IU kg(-1) on alternate days, according to their level of bleeding. CVAD insertion was at the discretion of the local health care team. Details regarding CVAD use during this protocol were analysed. RESULTS: Fifty six boys were enrolled, 21 required 25 CVADs due to difficult venous access. CVADs were inserted at a median age of 1.3 years (range: 0.6-2.1) and were removed at a median age of 8.7 years (range 6.3-11.8). Six participants experienced non-life threatening CVAD-complications, the most frequent being device malfunction requiring CVAD replacement (n = 4). Two boys were shown to have CVAD-associated thrombosis detected on routine imaging; one required removal due to infusion difficulties and the other was asymptomatic and did not require device removal. No CVAD-related infections were documented. CONCLUSION: Our study shows that the CHPS tailored prophylaxis regimen is associated with a decreased requirement for CVADs and with few device-related complications.