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2.
J Occup Rehabil ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769241

ABSTRACT

PURPOSE: Understanding sustainable employability (SE) of people with limited capability for work (LCW) due to physical or mental disability is crucial for the sustainable participation of this target group. Therefore, adequate measurement instruments for SE are needed. This study aims to validate a questionnaire to measure SE among people with LCW using a participatory approach, including person-job fit (PJ fit) and work-related sense of coherence (Work-SoC). METHODS: Existing scales for the main concepts were tested and adapted for face validity via cognitive interviews (n = 6), with the involvement of a co-researcher with LCW in the research team. Next, the questionnaire was administered among people with LCW (n = 248) to assess its factor structure (Confirmatory Factor Analysis) and reliability (Cronbach's alpha). RESULTS: Analysis of the cognitive interviews identified problems with clarity and readability of items, instructions and response categories of used (existing) scales. The main adjustments concerned the shortening of text length, the usage of familiar language and examples, and the addition of an introduction game. Most of the adapted SE indicator scales showed an overall good fit and acceptable-to-good internal reliability. The overall SE model had an overall good fit, and excluding 'internal employability' further improved this fit. PJ fit and Work-SoC had an acceptable/good model fit and internal consistency. CONCLUSION: The participatory validation process resulted in a validated and comprehensive questionnaire to measure SE, PJ fit and Work-SoC among people with LCW, which enables research into the development of their SE. This questionnaire can be utilised to contribute to a more inclusive labour market.

3.
Blood Adv ; 8(5): 1094-1104, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38191686

ABSTRACT

ABSTRACT: Patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBL-MYC/BCL2) respond poorly to immunochemotherapy compared with patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) without a MYC rearrangement. This suggests a negative impact of lymphoma-intrinsic MYC on the immune system. To investigate this, we compared circulating T cells and natural killer (NK) cells of patients with HGBL-MYC/BCL2 (n = 66), patients with DLBCL NOS (n = 53), and age-matched healthy donors (HDs; n = 16) by flow cytometry and performed proliferation, cytokine production, and cytotoxicity assays. Compared with HDs, both lymphoma subtypes displayed similar frequencies of CD8+ T cells but decreased CD4+ T cells. Regulatory T-cell (Treg) frequencies were reduced only in patients with DLBCL NOS. Activated (HLA-DR+/CD38+) T cells, PD-1+CD4+ T cells, and PD-1+Tregs were increased in both lymphoma subtypes, but PD-1+CD8+ T cells were increased only in HGBL-MYC/BCL2. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of senescent T cells than HDs. Functional assays showed no overt differences between both lymphoma groups and HDs. Deeper analyses revealed that PD-1+ T cells of patients with HGBL-MYC/BCL2 were exhausted with impaired cytokine production and degranulation. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of NK cells expressing inhibiting receptor NKG2A. Both lymphoma subtypes exhibited lower TIM-3+- and DNAM-1+-expressing NK cells. Although NK cells of patients with HGBL-MYC/BCL2 showed less degranulation, they were not defective in cytotoxicity. In conclusion, our results demonstrate an increased exhaustion in circulating T cells of patients with HGBL-MYC/BCL2. Nonetheless, the overall intact peripheral T-cell and NK-cell functions in these patients emphasize the importance of investigating potential immune evasion in the microenvironment of MYC-rearranged lymphomas.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Programmed Cell Death 1 Receptor , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Proto-Oncogene Proteins c-bcl-2/genetics , T-Lymphocytes/pathology , Killer Cells, Natural/pathology , Cytokines , Tumor Microenvironment
4.
Blood Cancer J ; 14(1): 2, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38177113

ABSTRACT

MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III-IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I-II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Proto-Oncogene Proteins c-bcl-2 , Humans , Prognosis , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-bcl-6 , Antineoplastic Combined Chemotherapy Protocols , Neoplasm Recurrence, Local , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Doxorubicin/therapeutic use
5.
Ultrasound Obstet Gynecol ; 62(6): 796-804, 2023 12.
Article in English | MEDLINE | ID: mdl-37204332

ABSTRACT

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Fetal Growth Retardation , Ultrasonography, Prenatal , Pregnancy , Infant, Newborn , Female , Humans , Infant , Fetal Growth Retardation/diagnostic imaging , Placenta , Fetal Development , Infant, Small for Gestational Age , Fetal Weight , Gestational Age , Predictive Value of Tests
6.
Blood Cancer J ; 13(1): 85, 2023 05 22.
Article in English | MEDLINE | ID: mdl-37217463

ABSTRACT

Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Large B-Cell, Diffuse , Humans , Middle Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/therapeutic use , Doxorubicin/adverse effects , Lenalidomide/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Prednisone/therapeutic use , Rituximab/therapeutic use , Treatment Outcome , Vincristine/adverse effects , Aged
9.
Ultrasound Obstet Gynecol ; 62(2): 209-218, 2023 08.
Article in English | MEDLINE | ID: mdl-36704993

ABSTRACT

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Cesarean Section , Fetal Growth Retardation , Ultrasonography, Prenatal , Female , Humans , Infant, Newborn , Pregnancy , Fetal Growth Retardation/diagnostic imaging , Fetal Weight , Gestational Age , Infant, Small for Gestational Age , Predictive Value of Tests , Pregnancy Trimester, Third , Ultrasonography, Prenatal/methods
12.
Blood Adv ; 5(8): 2196-2215, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33890981

ABSTRACT

Cell surface expression levels of GPRC5D, an orphan G protein-coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune cells, which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated MM patients. In addition, talquetamab has potent anti-MM activity in bone marrow (BM) samples from 45 patients, including those with high-risk cytogenetic aberrations. There was no difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) MM patients. Tumor cell lysis was accompanied by T-cell activation and degranulation, as well as production of pro-inflammatory cytokines. High levels of GPRC5D and high effector:target ratio were associated with improved talquetamab-mediated lysis of MM cells, whereas an increased proportion of T cells expressing PD-1 or HLA-DR, and elevated regulatory T-cell (Treg) counts were associated with suboptimal killing. In cell line experiments, addition of Tregs to effector cells decreased MM cell lysis. Direct contact with bone marrow stromal cells also impaired the efficacy of talquetamab. Combination therapy with daratumumab or pomalidomide enhanced talquetamab-mediated lysis of primary MM cells in an additive fashion. In conclusion, we show that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent. These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM.


Subject(s)
Antibodies, Bispecific , Multiple Myeloma , Antibodies, Bispecific/pharmacology , Antibodies, Bispecific/therapeutic use , Humans , Lymphocyte Activation , Multiple Myeloma/drug therapy , T-Lymphocytes, Regulatory
13.
Blood Cancer J ; 11(2): 38, 2021 02 18.
Article in English | MEDLINE | ID: mdl-33602901

ABSTRACT

Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20+ tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (n = 16), follicular lymphoma (n = 15), and mantle cell lymphoma (n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , B-Lymphocytes/drug effects , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Antibodies, Bispecific/pharmacology , Antigens, CD20/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Cell Line, Tumor , Humans , Lymphocyte Activation/drug effects , Lymphoma, Follicular/immunology , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Mantle-Cell/immunology , Lymphoma, Mantle-Cell/pathology , Tumor Cells, Cultured
14.
Cancers (Basel) ; 12(10)2020 Oct 20.
Article in English | MEDLINE | ID: mdl-33092116

ABSTRACT

Patients with MYC overexpressing high grade B cell lymphoma (HGBL) face significant dismal prognosis after treatment with standard immunochemotherapy regimens. Recent preclinical studies indicate that MYC not only contributes to tumorigenesis by its effects on cell proliferation and differentiation, but also plays an important role in promoting escape from anti-tumor immune responses. This is of specific interest, since reversing tumor immune inhibition with immunotherapy has shown promising results in the treatment of both solid tumors and hematological malignancies. In this review, we outline the current understanding of impaired immune responses in B cell lymphoid malignancies with MYC overexpression, with a particular emphasis on diffuse large B cell lymphoma. We also discuss clinical consequences of MYC overexpression in the treatment of HGBL with novel immunotherapeutic agents and potential future treatment strategies.

15.
BMC Pregnancy Childbirth ; 18(1): 192, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29855270

ABSTRACT

BACKGROUND: Although interventions in childbirth are important in order to prevent neonatal and maternal morbidity and mortality, non-indicated use may cause avoidable harm. Regional variations in intervention rates, which cannot be explained by maternal characteristics, may indicate over- and underuse. The aim of this study is to explore regional variations in childbirth interventions in the Netherlands and their associations with interventions and adverse outcomes, controlled for maternal characteristics. METHODS: Childbirth intervention rates were compared between twelve Dutch regions, using data from the national perinatal birth register for 2010-2013. All single childbirths from 37 weeks' gestation onwards were included. Primary outcomes were induction and augmentation of labour, pain medication, instrumental birth, caesarean section (prelabour, intrapartum) and paediatric involvement. Secondary outcomes were adverse neonatal and maternal outcomes. Multivariable logistic regression analyses were used to adjust for maternal characteristics. Associations were expressed in Spearman's rank correlation coefficients. RESULTS: Most variation was found for type of pain medication and paediatric involvement. Epidural analgesia rates varied from between 12 and 38% (nulliparous) and from between 5 and 14% (multiparous women). These rates were negatively correlated with rates of other pharmacological pain relief, which varied from between 15 and 43% (nulliparous) and from between 10 and 27% (multiparous). Rates of paediatric involvement varied from between 37 and 60% (nulliparous) and from between 26 and 43% (multiparous). For instrumental vaginal births, rates varied from between 16 and 19% (nulliparous) and from between 3 and 4% (multiparous). For intrapartum caesarean section, the variation was 13-15% and 5-6%, respectively. A positive correlation was found between intervention rates in midwife-led and obstetrician-led care at the onset of labour within the same region. Adverse neonatal and maternal outcomes were not lower in regions with higher intervention rates. Higher augmentation of labour rates correlated with higher rates of severe postpartum haemorrhage. CONCLUSIONS: Most variation was found for type of pain medication and paediatric involvement, and least for instrumental vaginal births and intrapartum caesarean sections. Care providers and policy makers should critically audit remarkable variations, since these may be unwarranted. Limited variation for some interventions may indicate consensus for their use. Further research should focus on variations in evidence-based interventions and indications for the use of interventions in childbirth.


Subject(s)
Delivery, Obstetric/statistics & numerical data , Maternal Health Services/statistics & numerical data , Pregnancy Outcome/epidemiology , Adult , Analgesia, Obstetrical/statistics & numerical data , Cesarean Section/statistics & numerical data , Female , Geography , Humans , Labor, Induced/statistics & numerical data , Logistic Models , Multivariate Analysis , Netherlands/epidemiology , Pediatrics/statistics & numerical data , Pregnancy , Registries , Statistics, Nonparametric
17.
BMC Pregnancy Childbirth ; 16(1): 363, 2016 11 22.
Article in English | MEDLINE | ID: mdl-27871257

ABSTRACT

BACKGROUND: In several developed countries women with a low risk of complications during pregnancy and childbirth can make choices regarding place of birth. In the Netherlands, these women receive midwife-led care and can choose between a home or hospital birth. The declining rate of midwife-led home births alongside the recent debate on safety of home births in the Netherlands, however, suggest an association of choice of birth place with psychological factors related to safety and risk perception. In this study associations of pregnancy related anxiety and general anxious or depressed mood with (changes in) planned place of birth were explored in low risk women in midwife-led care until the start of labour. METHODS: Data (n = 2854 low risk women in midwife-led care at the onset of labour) were selected from the prospective multicenter DELIVER study. Women completed the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R) to assess pregnancy related anxiety and the EuroQol-6D (EQ-6D) for an anxious and/or depressed mood. RESULTS: A high PRAQ-R score was associated with planned hospital birth in nulliparous (aOR 1.92; 95% CI 1.32-2.81) and parous women (aOR 2.08; 95% CI 1.55-2.80). An anxious or depressed mood was associated with planned hospital birth (aOR 1.58; 95% CI 1.20-2.08) and with being undecided (aOR 1.99; 95% CI 1.23-2.99) in parous women only. The majority of women did not change their planned place of birth. Changing from an initially planned home birth to a hospital birth later in pregnancy was, however, associated with becoming anxious or depressed after 35 weeks gestation in nulliparous women (aOR 4.17; 95% CI 1.35-12.89) and with pregnancy related anxiety at 20 weeks gestation in parous women (aOR 3.91; 95% CI 1.32-11.61). CONCLUSION: Low risk women who planned hospital birth (or who were undecided) more often reported pregnancy related anxiety or an anxious or depressed mood. Women who changed from home to hospital birth during pregnancy more often reported pregnancy related anxiety or an anxious or depressed mood in late pregnancy. Anxiety should be adequately addressed in the process of informed decision-making regarding planned place of birth in low risk women.


Subject(s)
Anxiety/psychology , Choice Behavior , Depression/psychology , Parturition/psychology , Pregnancy Complications/psychology , Adult , Decision Making , Female , Humans , Labor, Obstetric/psychology , Midwifery , Netherlands , Pregnancy , Prenatal Care/psychology , Prospective Studies , Young Adult
18.
BMC Pregnancy Childbirth ; 16(1): 329, 2016 10 28.
Article in English | MEDLINE | ID: mdl-27793112

ABSTRACT

BACKGROUND: The use of interventions in childbirth has increased the past decades. There is concern that some women might receive more interventions than they really need. For low-risk women, midwife-led birth settings may be of importance as a counterbalance towards the increasing rate of interventions. The effect of planned place of birth on interventions in the Netherlands is not yet clear. This study aims to give insight into differences in obstetric interventions and maternal outcomes for planned home versus planned hospital birth among women in midwife-led care. METHODS: Women from twenty practices across the Netherlands were included in 2009 and 2010. Of these, 3495 were low-risk and in midwife-led care at the onset of labour. Information about planned place of birth and outcomes, including instrumental birth (caesarean section, vacuum or forceps birth), labour augmentation, episiotomy, oxytocin in third stage, postpartum haemorrhage >1000 ml and perineal damage, came from the national midwife-led care perinatal database, and a postpartum questionnaire. RESULTS: Women who planned home birth more often had spontaneous birth (nulliparous women aOR 1.38, 95 % CI 1.08-1.76, parous women aOR 2.29, 95 % CI 1.21-4.36) and less often episiotomy (nulliparous women aOR 0.73, 0.58-0.91, parous women aOR 0.47, 0.33-0.68) and use of oxytocin in the third stage (nulliparous women aOR 0.58, 0.42-0.80, parous women aOR 0.47, 0.37-0.60) compared to women who planned hospital birth. Nulliparous women more often had anal sphincter damage (aOR 1.75, 1.01-3.03), but the difference was not statistically significant if women who had caesarean sections were excluded. Parous women less often had labour augmentation (aOR 0.55, 0.36-0.82) and more often an intact perineum (aOR 1.65, 1.34-2.03). There were no differences in rates of vacuum/forceps birth, unplanned caesarean section and postpartum haemorrhage >1000 ml. CONCLUSIONS: Women who planned home birth were more likely to give birth spontaneously and had fewer medical interventions.


Subject(s)
Delivery, Obstetric/statistics & numerical data , Home Childbirth/statistics & numerical data , Midwifery/statistics & numerical data , Perinatal Care/statistics & numerical data , Adult , Cesarean Section/statistics & numerical data , Cohort Studies , Delivery, Obstetric/methods , Episiotomy/statistics & numerical data , Female , Humans , Labor Stage, Third , Medical Overuse , Netherlands/epidemiology , Oxytocics/therapeutic use , Oxytocin/therapeutic use , Parity , Perinatal Care/methods , Perineum/injuries , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/etiology , Pregnancy , Pregnancy Outcome , Risk , Young Adult
20.
Eur J Cancer ; 55: 140-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26820684

ABSTRACT

In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Gene Rearrangement , Lymphoma, Large B-Cell, Diffuse/drug therapy , Proto-Oncogene Proteins c-myc/genetics , Adult , Aged , Female , Genetic Predisposition to Disease , Humans , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Molecular Targeted Therapy , Patient Selection , Phenotype , Precision Medicine , Predictive Value of Tests , Survival Analysis , Treatment Outcome
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