A Dutch randomized controlled study shows autologous fat transfer with pre-expansion is more cost-effective in the long term than implants.

BACKGROUND: One in seven women will develop breast cancer, making it the most common female cancer worldwide. Consequently, breast cancer-related treatment, including breast reconstruction, impacts societal costs. Autologous fat transfer (AFT) is a relatively new breast reconstruction technique; however, several surgeries are necessary. This study investigates if AFT with pre-expansion is more cost-effective than implant-based reconstruction (IBR). METHODS: Seven centers assigned patients randomly from 2015 to 2021 to evaluate costs and EQ-5D-5L quality-adjusted life years (QALY) of AFT vs. IBR at 12 months postoperative. Costs were calculated, including direct costs related to treatment and PROductivity and DISease Questionnaire, to estimate productivity loss (indirect costs). Sensitivity analyses were performed for 10- and 30 years to estimate costs for patients replacing or explanting their breast implants over time. RESULTS: A total of 152 women, of which 91 received AFT (mean age 49.3) and 80 IBR (mean age 49.1). The mean EQ-5D-5L QALY in the AFT group was 0.83, compared with the IBR group of 0.79. Total costs for AFT at 12 months postoperative were higher than IBR (incremental cost: €6763.59). Sensitivity analyses for 10- and 30-year scenarios showed mean incremental costs of respectively €2586.56 and €680.22. CONCLUSION: Mean EQ-5D-5L QALY and costs were higher for AFT over the first year after reconstruction. However, these costs were low; therefore, AFT was estimated to be more cost-effective over the 10- and 30-year period since no additional surgeries are necessary for this group. Larger cohorts are required to confirm AFT is more cost-effective in the long term.

Risk of major postoperative complications in breast reconstructive surgery with and without an acellular dermal matrix: A development of a prognostic prediction model.

Introduction: Acellular dermal matrices (ADM) have been suggested to allow for different approaches and reduce the risk of postoperative complications in implant-based breast surgery. Surgeons seem to embrace ADMs around the world, although a lack of consistent evidence regarding the factors that increase the risk of major postoperative complications remains. Purpose: To develop and internally validate a model to predict the risk of a major postoperative complication in breast reconstructive surgery with and without an ADM. Methodology: The DBIR is an opt-out registry that holds characteristics of all breast implant surgeries in the Netherlands since 2015. Using a literature-driven preselection of predictors, multivariable mixed-effects logistic regression modelling was used to develop the prediction model. Results: A total of 2939 breasts were eligible, of which 11% underwent an ADM-assisted procedure (single-stage or two-stage). However, 31% underwent a two-stage procedure (with or without the use of ADM). Of all breasts, 10.2% developed a major postoperative complication. Age (OR 1.01), delayed timing (OR 0.71), and two-stage technique (OR 4.46) were associated with the outcome. Conclusion: The data suggest that ADM use was not associated with a major postoperative complication, while two-stage reconstructions were strongly associated with an increased risk of major complications. Despite these findings, ADMs are not as popular in the Netherlands as in the USA. The predictive capabilities of the developed model are mediocre to poor, but because of the above findings, we believe that the role of the two-stage technique as a golden standard should be put up for debate.

Towards evidence based plastic surgery; how a national research agenda can unite research.

We describe the development of the Research Agenda of the Dutch Society for Plastic Surgery, supported and democratically created by plastic surgeons, patients, and other stakeholders. The agenda contains the 10 most relevant knowledge gaps encountered in clinical practice, as prioritized by the abovementioned groups. The aim is to stimulate national collaborations and research networks to initiate trials to answer these knowledge gaps. The agenda will be renewed periodically to stay relevant. We encourage other national and international associations to develop a research agenda within their field, and intensify their research network and improve research quality.

How to improve patient safety and quality of care in breast implant surgery? First outcomes from the Dutch Breast Implant Registry (2015-2017).

BACKGROUND: Although the use of breast implants is generally considered to be safe, breast implants are associated with short- and long-term complications. To evaluate and improve the quality of breast implant surgery, and increase our knowledge of implant performance, the national Dutch Breast Implant Registry (DBIR) was established in 2015. DBIR is one of the first up-and-running breast implant registries worldwide and follows an opt-out structure. OBJECTIVE: This article provides an overview of the first outcomes and experiences of the DBIR. METHODS: The national coverage of DBIR was studied using data from the Dutch Health and Youth Care Inspectorate. The incidence rate of breast implants was calculated for 2016 and 2017, and patient, device, and surgery characteristics were compared between cosmetic breast augmentations or reconstructive indications. Four infection control, measures were selected to demonstrate the variation in the Dutch clinical practice. RESULTS: In 2016, 95% of the hospitals and 78% of the private clinics participated in DBIR. Between 2015 and 2017, a total of 15,049 patients and 30,541 breast implants were included. A minimum breast implant incidence rate of 1 per 1,691 women could be determined for 2017. The majority of devices were inserted for a cosmetic indication (85.2%). In general, patient, device, and surgery characteristics differed per indication group. Substantial variation was seen in the use of infection control measures (range 0-100%). CONCLUSION: Preliminary results obtained from DBIR show high national participation rates and support further developments toward the improvement of breast implant surgery and patient safety.

Predictors of complications after direct-to-implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial.

BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. RESULTS: Fifty-nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. CONCLUSION: Breast size appeared to be the most significant predictor of complications in DTI ADM-assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl).

Does 2-Stage Implant-Based Breast Reconstruction Allow for a Larger Volume of the Definite Implant Compared With 1-Stage Reconstruction?

INTRODUCTION: Breast reconstruction using implants is still the main breast reconstruction technique worldwide. Current debate within implant-based breast reconstruction is whether to perform a 1-stage (direct implant) or 2-stage (tissue expander/implant) reconstruction. Volume differences between a woman's native breast and changes in volume after breast reconstruction might be an important factor for a patient's choice between these types of reconstruction. Three-dimensional imaging facilitates objective breast volume estimates. The goal of this study was to investigate differences between the patient's natural breast and the volume after completed breast reconstruction. One- and two-stage implant-based breast reconstruction techniques were compared. Finally, it was assessed whether patient satisfaction is causally related with the final breast volume after reconstruction. METHODS AND RESULTS: A total of 38 patients were included in the study, including 35 two-stage breast reconstructions and 27 one-stage reconstructions. Preoperative and postoperative 3-dimensional images of the breast with the Vectra XT Imaging system were taken. Volume analysis was performed to estimate the patient's native breast volume. Implant size were derived from the operation report. A mean volume reduction for the 1-stage reconstruction group was found -1 mL, whereas an increase of +80 mL was found in the 2-stage reconstruction group (P < 0.005). Patient satisfaction related to volume outcome was not significantly different between both groups, using the Breast-Q questionnaire. CONCLUSIONS: This study shows that a 2-stage breast reconstruction has the potential of an increased breast volume compared with a similar breast volume in 1-stage reconstruction.

Understanding the effects of time on collaborative learning processes in problem based learning: a mixed methods study.

Little is known how time influences collaborative learning groups in medical education. Therefore a thorough exploration of the development of learning processes over time was undertaken in an undergraduate PBL curriculum over 18 months. A mixed-methods triangulation design was used. First, the quantitative study measured how various learning processes developed within and over three periods in the first 1,5 study years of an undergraduate curriculum. Next, a qualitative study using semi-structured individual interviews focused on detailed development of group processes driving collaborative learning during one period in seven tutorial groups. The hierarchic multilevel analyses of the quantitative data showed that a varying combination of group processes developed within and over the three observed periods. The qualitative study illustrated development in psychological safety, interdependence, potency, group learning behaviour, social and task cohesion. Two new processes emerged: 'transactive memory' and 'convergence in mental models'. The results indicate that groups are dynamic social systems with numerous contextual influences. Future research should thus include time as an important influence on collaborative learning. Practical implications are discussed.

Visualising the invisible: a network approach to reveal the informal social side of student learning.

World-wide, universities in health sciences have transformed their curriculum to include collaborative learning and facilitate the students' learning process. Interaction has been acknowledged to be the synergistic element in this learning context. However, students spend the majority of their time outside their classroom and interaction does not stop outside the classroom. Therefore we studied how informal social interaction influences student learning. Moreover, to explore what really matters in the students learning process, a model was tested how the generally known important constructs-prior performance, motivation and social integration-relate to informal social interaction and student learning. 301 undergraduate medical students participated in this cross-sectional quantitative study. Informal social interaction was assessed using self-reported surveys following the network approach. Students' individual motivation, social integration and prior performance were assessed by the Academic Motivation Scale, the College Adaption Questionnaire and students' GPA respectively. A factual knowledge test represented student' learning. All social networks were positively associated with student learning significantly: friendships (ß = 0.11), providing information to other students (ß = 0.16), receiving information from other students (ß = 0.25). Structural equation modelling revealed a model in which social networks increased student learning (r = 0.43), followed by prior performance (r = 0.31). In contrast to prior literature, students' academic motivation and social integration were not associated with students' learning. Students' informal social interaction is strongly associated with students' learning. These findings underline the need to change our focus from the formal context (classroom) to the informal context to optimize student learning and deliver modern medics.

Self-monitoring as a familial vulnerability marker for psychosis: an analysis of patients, unaffected siblings and healthy controls.

BACKGROUND: Alterations in self-monitoring have been reported in patients with psychotic disorders, but it remains unclear to what degree they represent true indicators of familial vulnerability for psychosis. METHOD: An error-correction action-monitoring task was used to examine self-monitoring in 42 patients with schizophrenia, 32 of their unaffected siblings and 41 healthy controls. RESULTS: Significant between-group differences in self-monitoring accuracy were found (χ2=29.3, p<0.0001), patients performing worst and unaffected siblings performing at an intermediate level compared to controls (all between-group differences p<0.05). In the combined group of healthy controls and unaffected siblings, detection accuracy was associated with positive schizotypy as measured by the Structured Interview for Schizotypy - Revised (SIS-R) (ß=-0.16, s.e.=0.07, p=0.026), but not with negative schizotypy (ß=-0.05, s.e.=0.12, p=0.694). In patients, psychotic symptoms were not robustly associated with detection accuracy (ß=-0.01, s.e.=0.01, p=0.094), although stratified analysis revealed suggestive evidence for association in patients not currently using antipsychotic medication (ß=-0.03, s.e.=0.01, p=0.052), whereas no association was found in patients on antipsychotic medication (ß=-0.01, s.e.=0.01, p=0.426). A similar pattern of associations was found for negative symptoms. CONCLUSIONS: Alterations in self-monitoring may be associated with familial risk and expression of psychosis. The association between psychotic symptoms and self-monitoring in patients may be affected by antipsychotic medication, which may explain previous inconsistencies in the literature.

Urinary metabolite profile of phenyl and o-cresyl glycidyl ether in rats: identification of a novel pathway leading to N-acetylserine O-conjugates.

The urinary excretion of metabolites of phenyl glycidyl ether (PGE) and o-cresyl glycidyl ether (o-CGE) was investigated in rats. Urine was collected, in fractions, from rats intraperitoneally administered PGE or o-CGE in doses ranging from 0.033 to 1.0 mmol/kg. The metabolites were extracted from acidified urine with ethyl acetate or diethyl ether, and their identity was elucidated by GC/MS analysis. The epoxide of PGE can be inactivated by glutathione (GSH) conjugation or epoxide hydrolysis. After further metabolism, these routes lead to the urinary excretion of phenyl glycidyl ether mercapturic acid (PGEMA) and 3-(phenyloxy)lactic acid (POLA). The excretion of PGEMA and POLA was described before and is confirmed in this study. Additionally, a new metabolite was identified as N-acetyl-O-phenylserine (NAPS), which is proposed to be formed from POLA by subsequent oxidation, transamination, and N-acetylation. For PGEMA a linear dose-excretion relationship was found (r2 = 0.988), and the percentage of the dose excreted declined from 27% to 10% with increasing PGE dose. For NAPS also a linear dose-excretion relationship was found (r2 = 0.985), and NAPS accounted for 27% of the PGE dose. The excretion of PGEMA and NAPS was rather fast: 93% and 75%, respectively, of the respective total cumulative amounts excreted was already collected within 6 h after administration. The urinary metabolite profile of o-CGE was not investigated in rats before. Three urinary metabolites of o-CGE were identified, namely, 3-(o-cresyloxy)lactic acid (COLA), o-cresyl glycidyl ether mercapturic acid (o-CGEMA), and N-acetyl-O-(o-cresyl)serine (NACS), showing that the metabolite profiles of PGE and o-CGE are comparable. Up to a o-CGE dose of 0.333 mmol/kg, the excretion of o-CGEMA was linear (r2 = 0.997), while above this dose the excretion did not increase anymore. The percentage of the o-CGE dose excreted as o-CGEMA declined from 31% to 11% with increasing dose. Again 93% of the total cumulative amount of o-CGEMA excreted was collected within 6 h after administration of o-CGE. Analytical methods were developed for the quantitative determination of mercapturic acid metabolites of PGE and o-CGE. These methods were sufficiently sensitive for their determination in urine of rats administered PGE or o-CGE in the dose range applied. It is anticipated that the analytical methods developed are also sufficiently sensitive to investigate excretion of the mercapturic acid metabolites in humans occupationally exposed to low air concentrations (<6 mg/m3 of air, 8h-TWA) of PGE or o-CGE.

Radiation-induced structural changes in membrane proteins of human erythrocytes and ghosts and the relation to cellular morphology.

Isolated human erythrocytes and ghosts were irradiated with X-rays under different experimental conditions. The effect of the radiation treatment was examined with regard to the structure of membrane proteins as well as to the morphology of whole cells and ghosts. From sodium dodecyl sulphate/polyacrylamide gel electrophoresis it is concluded that spectrin (band 1 and 2) is the most radiosensitive of the membrane proteins examined. X-irradiation of cells and ghosts induced covalent cross-linking of a small fraction of membrane proteins. In the protein aggregates thus formed spectrin was found to be the major component. Molecular disulphide (-SS-) bridges seemed to account for part of the cross-links observed. Some nondisulphide cross-links were also found, especially when ghosts were irradiated. Significant amounts of spectrin aggregates were formed during post-irradiation incubation at 37 degrees C but not at 4 degrees C. In the intact cell a transformation in shape from discocyte to echinocyte accompanied the process of post-irradiation spectrin aggregation. The characteristics of both processes, such as their reversibility with adenosine, point to a metabolic involvement. It is shown that there is no causal relationship between the two phenomena observed. The possible cause of the post-irradiation effects and the parallelism with similar processes in nonirradiated metabolically depleted cells is discussed.