Abstract
STUDY QUESTION
Do children conceived by ART have an increased risk of cancer?
SUMMARY ANSWER
Overall, ART-conceived children do not appear to have an increased risk of cancer.
WHAT IS KNOWN ...ALREADY
Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce.
STUDY DESIGN, SIZE, DURATION
A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001.
PARTICIPANTS/MATERIALS, SETTING, METHODS
All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios HRs) and with the general population (standardized incidence ratios SIRs).
MAIN RESULTS AND THE ROLE OF CHANCE
The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children.
LIMITATIONS, REASONS FOR CAUTION
Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare.
WIDER IMPLICATIONS OF THE FINDINGS
Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.
Background
Training residents in delivering high-value, cost-conscious care (HVCCC) is crucial for a sustainable healthcare. A supportive learning environment is key. Yet, stakeholders’ attitudes ...toward HVCCC in residents’ learning environment are unknown.
Objective
We aimed to measure stakeholders’ HVCCC attitudes in residents’ learning environment, compare these with resident perceptions of their attitudes, and identify factors associated with attitudinal differences among each stakeholder group.
Design
We conducted a cross-sectional survey across the Netherlands between June 2017 and December 2018.
Participants
Participants were 312 residents, 305 faculty members, 53 administrators, and 1049 patients from 66 (non)academic hospitals.
Main Measures
Respondents completed the Maastricht HVCCC Attitude Questionnaire (MHAQ), containing three subscales: (1) high-value care, (2) cost incorporation, (3) perceived drawbacks. Additionally, resident respondents estimated the HVCCC attitudes of other stakeholders, and answered questions on job demands and resources. Univariate and multivariate analyses were used to analyze data.
Key Results
Attitudes differed on all subscales: faculty and administrators reported more positive HVCCC attitudes than residents (
p
≤ 0.05), while the attitudes of patients were less positive (
p
≤ 0.05). Residents underestimated faculty’s (
p
< 0.001) and overestimated patients’ HVCCC attitudes (
p
< 0.001). Increasing age was, among residents and faculty, associated with more positive attitudes toward HVCCC (
p
≤ 0.05). Lower perceived health quality was associated with less positive attitudes among patients (
p
< 0.001). The more autonomy residents perceived, the more positive their HVCCC attitude (
p
≤ 0.05).
Conclusions
Attitudes toward HVCCC vary among stakeholders in the residency learning environment, and residents misjudge the attitudes of both faculty and patients. Faculty and administrators might improve their support to residents by more explicitly sharing their thoughts and knowledge on HVCCC and granting residents autonomy in clinical practice.
The clinical workplace offers residents many opportunities for learning. Reflection on workplace experiences drives learning and development because experiences potentially make residents reconsider ...existing knowledge, action repertoires and beliefs. As reflective learning in the workplace cannot be taken for granted, we aimed to gain a better insight into the process of why residents identify experiences as learning moments, and how residents reflect on these moments.
This study draws on semi-structured interviews with 33 medical residents. Interviews explored how residents identified learning moments and how they reflected on such moments, both in-action and on-action. Aiming for extensive explanations on the process of reflection, open-ended questions were used that built on and deepened residents' answers. After interviews were transcribed verbatim, a within-case and cross-case analysis was conducted to build a general pattern of explanation.
The data analysis yielded understanding of the crucial role of the social context. Interactions with peers, supervisors, and patients drive reflection, because residents want to measure up to their peers, meet supervisors' standards, and offer the best patient care. Conversely, quality and depth of reflection sometimes suffer, because residents prioritize patient care over learning. This urges them to seek immediate solutions or ask their peers or supervisor for advice, rather than reflectively deal with a learning moment themselves. Peer discussions potentially enhance deep reflection, while own supervisor involvement sometimes feels unsafe.
Our results adds to our understanding of the social-constructivist nature of reflection. We suggest that feelings of self-preservation during interactions with peers and supervisors in a highly demanding work environment shape reflection. Support from peers or supervisors helps residents to instantly deal with learning moments more easily, but it also makes them more dependent on others for learning. Since residents' devotion to patient care obscures the reflection process, residents need more dedicated time to reflect. Moreover, to elaborate deeply on learning moments, a supportive and safe learning climate with peers and supervisors is recommended.
Abstract Obesity is an increasing problem worldwide. The number of people with obesity doubled since the 1980's to affect an estimated 671 million people worldwide. Obese patients in general have an ...altered respiratory physiology and can have an impaired lung function, which leads to an increased risk of developing pulmonary complications during anaesthesia and after bariatric surgery (approximately 8%). Therefore the respiratory management of the bariatric surgical patient provides a number of challenges. This review will focus on the perioperative respiratory care in bariatric surgical patients discussing respiratory physiology in the obese and perioperative respiratory care in bariatric surgery. Finally the value of preoperative pulmonary function testing and preoperative OSAS screening will be discussed.
Abstract
STUDY QUESTION
Do cumulative live birth rates (CLBRs) over multiple IVF/ICSI cycles confirm the low prognosis in women stratified according to the POSEIDON criteria?
SUMMARY ANSWER
The CLBR ...of low-prognosis women is ~56% over 18 months of IVF/ICSI treatment and varies between the POSEIDON groups, which is primarily attributable to the impact of female age.
WHAT IS KNOWN ALREADY
The POSEIDON group recently proposed a new stratification for low-prognosis women in IVF/ICSI treatment, with the aim to define more homogenous populations for clinical trials and stimulate a patient-tailored therapeutic approach. These new criteria combine qualitative and quantitative parameters to create four groups of low-prognosis women with supposedly similar biologic characteristics.
STUDY DESIGN, SIZE, DURATION
This study analyzed the data of a Dutch multicenter observational cohort study including 551 low-prognosis women, aged <44 years, who initiated IVF/ICSI treatment between 2011 and 2014 and were treated with a fixed FSH dose of 150 IU/day in the first treatment cycle.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Low-prognosis women were categorized into one of the POSEIDON groups based on their age (younger or older than 35 years), anti-Müllerian hormone (AMH) level (above or below 0.96 ng/ml), and the ovarian response (poor or suboptimal) in their first cycle of standard stimulation. The primary outcome was the CLBR over multiple complete IVF/ICSI cycles, including all subsequent fresh and frozen-thawed embryo transfers, within 18 months of treatment. Cumulative incidence curves were obtained using an optimistic and a conservative analytic approach.
MAIN RESULTS AND THE ROLE OF CHANCE
The CLBR of the low-prognosis women was on average ~56% over 18 months of IVF/ICSI treatment. Younger unexpected poor (n = 38) and suboptimal (n = 179) responders had a CLBR of ~65% and ~68%, respectively, and younger expected poor responders (n = 65) had a CLBR of ~59%. The CLBR of older unexpected poor (n = 41) and suboptimal responders (n = 102) was ~42% and ~54%, respectively, and of older expected poor responders (n = 126) ~39%. For comparison, the CLBR of younger (n = 164) and older (n = 78) normal responders with an adequate ovarian reserve was ~72% and ~58% over 18 months of treatment, respectively. No large differences were observed in the number of fresh treatment cycles between the POSEIDON groups, with an average of two fresh cycles per woman within 18 months of follow-up.
LIMITATIONS, REASONS FOR CAUTION
Small numbers in some (sub)groups reduced the precision of the estimates. However, our findings provide the first relevant indication of the CLBR of low-prognosis women in the POSEIDON groups. Small FSH dose adjustments between cycles were allowed, inducing therapeutic disparity. Yet, this is in accordance with current daily practice and increases the generalizability of our findings.
WIDER IMPLICATIONS OF THE FINDINGS
The CLBRs vary between the POSEIDON groups. This heterogeneity is primarily determined by a woman’s age, reflecting the importance of oocyte quality. In younger women, current IVF/ICSI treatment reaches relatively high CLBR over multiple complete cycles, despite reduced quantitative parameters. In older women, the CLBR remains relatively low over multiple complete cycles, due to the co-occurring decline in quantitative and qualitative parameters. As no effective interventions exist to counteract this decline, clinical management currently relies on proper counselling.
STUDY FUNDING/COMPETING INTEREST(S)
No external funds were obtained for this study. J.A.L. is supported by a Research Fellowship grant and received an unrestricted personal grant from Merck BV. S.C.O., T.C.v.T., and H.L.T. received an unrestricted personal grant from Merck BV. C.B.L. received research grants from Merck, Ferring, and Guerbet. K.F. received unrestricted research grants from Merck Serono, Ferring, and GoodLife. She also received fees for lectures and consultancy from Ferring and GoodLife. A.H. declares that the Department of Obstetrics and Gynaecology, University Medical Centre Groningen received an unrestricted research grant from Ferring Pharmaceuticals BV, the Netherlands. J.S.E.L. has received unrestricted research grants from Ferring, Zon-MW, and The Dutch Heart Association. He also received travel grants and consultancy fees from Danone, Euroscreen, Ferring, AnshLabs, and Titus Healthcare. B.W.J.M. is supported by an National Health and Medical Research Council Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, and Guerbet. He also received a research grant from Merck BV and travel support from Guerbet. F.J.M.B. received monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands) and Ferring Pharmaceuticals BV (the Netherlands) for advisory work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development, and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare.
TRIAL REGISTRATION NUMBER
Not applicable.
ABSTRACT
Osteoporosis is highly prevalent in chronic obstructive pulmonary disease (COPD) patients and has been related to several clinical features. However, most studies have been in relatively ...small COPD cohorts. Therefore, the objectives of this study were to compare bone attenuation measured on low‐dose chest computed tomography (CT) between COPD subjects and smoker and nonsmoker controls, and to relate bone attenuation to clinical parameters, inflammatory biomarkers, and outcomes in a large, well‐characterized COPD cohort. We studied 1634 COPD subjects, 259 smoker controls, and 186 nonsmoker controls who participated in a large longitudinal study (ECLIPSE). We measured bone attenuation, extent of emphysema, and coronary artery calcification (Agatston score) on baseline CT scans, and clinical parameters, inflammatory biomarkers, and outcomes. Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls (164.9 ± 49.5 Hounsfield units HU versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU, p < 0.001). Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation correlated positively with forced expiratory volume in 1 second (FEV1, r = 0.062, p = 0.014), FEV1/forced vital capacity (FVC) ratio (r = 0.102, p < 0.001), body mass index (r = 0.243, p < 0.001), fat‐free mass index (FFMI, r = 0.265, p < 0.001), and C‐reactive protein (r = 0.104, p < 0.001), and correlated negatively with extent of emphysema (r = −0.090, p < 0.001), Agatston score (r = −0.177, p < 0.001), and interleukin‐8 (r = −0.054, p = 0.035). In a multiple regression model, older age, lower FFMI and higher Agatston score were associated with lower bone attenuation. Lower bone attenuation was associated with higher exacerbation (r = −0.057, p = 0.022) and hospitalization (r = −0.078, p = 0.002) rates but was not associated with all‐cause mortality. In conclusion, CT‐measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls, after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation was associated with age, body composition, and coronary artery calcification but was not associated with all‐cause mortality.
Residents have to learn to provide high value, cost-conscious care (HVCCC) to counter the trend of excessive healthcare costs. Their learning is impacted by individuals from different stakeholder ...groups within the workplace environment. These individuals' attitudes toward HVCCC may influence how and what residents learn. This study was carried out to develop an instrument to reliably measure HVCCC attitudes among residents, staff physicians, administrators, and patients. The instrument can be used to assess the residency-training environment.
The Maastricht HVCCC Attitude Questionnaire (MHAQ) was developed in four phases. First, we conducted exploratory factor analyses using original data from a previously published survey. Next, we added nine items to strengthen subscales and tested the new questionnaire among the four stakeholder groups. We used exploratory factor analysis and Cronbach's alphas to define subscales, after which the final version of the MHAQ was constructed. Finally, we used generalizability theory to determine the number of respondents (residents or staff physicians) needed to reliably measure a specialty attitude score.
Initial factor analysis identified three subscales. Thereafter, 301 residents, 297 staff physicians, 53 administrators and 792 patients completed the new questionnaire between June 2017 and July 2018. The best fitting subscale composition was a three-factor model. Subscales were defined as high-value care, cost incorporation, and perceived drawbacks. Cronbach's alphas were between 0.61 and 0.82 for all stakeholders on all subscales. Sufficient reliability for assessing national specialty attitude (G-coefficient > 0.6) could be achieved from 14 respondents.
The MHAQ reliably measures individual attitudes toward HVCCC in different stakeholders in health care contexts. It addresses key dimensions of HVCCC, providing content validity evidence. The MHAQ can be used to identify frontrunners of HVCCC, pinpoint aspects of residency training that need improvement, and benchmark and compare across specialties, hospitals and regions.
Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to ...cumulative live birth rate and safety?
Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed.
Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response.
Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders.
Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective.
We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 95%CI, 0.85-1.07, P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 95%CI, 0.28-0.71, P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 95%CI, 0.38-4.07, P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 95%CI, -479-325), there was no dominant strategy in the economic analysis.
Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings.
In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates.
This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare.
Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657.
20 December 2010.
12 May 2011.
Colorectal cancer is a rising problem, as the incidence increases with age. In most cases the goal of treatment is oncological resection followed by adjuvant chemotherapy in order to optimize the ...survival. In this case report we present a 93-year-old patient with a sigmoid carcinoma inside an irreducible inguinal hernia, which was diagnosed prior to surgery. We chose to perform a sigmoid resection through an oblique inguinal incision as a safer alternative to laparotomy.
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