Background: Terminally ill people represent a unique group where suicide may be considered as a rational and ethical act. Given their limited life expectancy and wish to reduce suffering, terminally ill people may exert their self-determination and autonomy by ending their life. Objectives: The aims of this study are to [i.] compare the socio-demographic and clinical variables of two groups of older people who completed suicide: those with advanced cancer and those without; and [ii] examine qualitatively whether the advanced cancer cases could be defined as rational suicide.
Methods: The New Zealand Coronial Services provided records of all suicide cases aged 65 years and over (n=225) between July 2007 and December 2012. We were able to determine whether there was an advanced cancer in 214 cases.
Findings: 23 (10.7%) older people who completed suicide were diagnosed with an advanced cancer. Bivariate analysis found that they were more likely to be male (91.3% versus 72.3%, p=0.048), married or in a defacto relationship (78.3% versus 46.1%, p=0.014); but less likely to have a diagnosis of depression (8.7% versus 46.6%, p=0.001), previous contact with psychiatric services (4.5% versus 35.0%, p=0.004) and past suicide attempt (9.1% versus 28.8%, p=0.048). Next to that the circumstances of 82.6 % of the advanced cancer patients who died by suicide were conceived as ‘understandable for uninvolved observers’.
Conclusions: With a growing elderly population and higher rates of suicide within the elderly, late-life suicide is becoming more prevalent. The diagnosis of terminal illness is higher amongst elderly. Further research is needed to delineate motives and suicide risks for terminally ill patients. More knowledge and understanding can offer the patient more targeted care and an earlier/better relieve of their mental and physical suffering.
The introduction of platinum-based chemotherapy for treatment of metastatic testicular cancer in the late 1970s has led to an increase in survival rates and a growing cohort of testicular cancer survivors. Consequently, attention for long-term adverse effects of treatment has increased. Nephrotoxicity is an important adverse effect of platinum-based chemotherapy. However, data on renal function more than 20 years after treatment is lacking.
1. To assess renal function and glomerular damage in very long term survivors of testicular cancer treated with cisplatin combination chemotherapy, compared with an age-matched control group who have not been treated for any type of cancer.
2. To investigate disease and treatment characteristics of testicular cancer associated with decreased renal function.
3. To investigate comorbidities and cardiovascular risk factors associated with decreased renal function.
Renal function, measured by mean creatinine clearance (CRCL) of two 24-hour urine collections, was assessed in 54 patients treated with platinum-based chemotherapy for testicular cancer between 1977 and 1996 and compared with a group of 27 healthy controls. Glomerular damage was measured by albuminuria and proteinuria and compared between the two groups. Furthermore, disease and treatment characteristics, comorbidities and cardiovascular risk factors were evaluated.
Median CRCL in 54 chemotherapy-treated testicular cancer survivors was 102.8 ml/min/1.73m2 versus 125.8 ml/min/1.73m2 in healthy controls (p<0.001). 20 participants had a CRCL <90 ml/min/1.73m2, of which nineteen (95%) were treated with chemotherapy (p=0.002). No significant difference in presence of albuminuria and proteinuria was observed. Cumulative dose of cisplatin did not correlate with CRCL (spearman’s rho=0.006, p=0.967). In testicular cancer survivors, CRCL before start of chemotherapy was the only factor associated with a decreased renal function, after a median follow-up of 27 years. No differences in comorbidities and cardiovascular risk factors were observed in patients with a decreased and normal renal function.
Renal function in patients treated with platinum-based chemotherapy for testicular cancer more than 20 years ago is decreased compared to healthy controls. After a median follow up of 27 years, over a third of patients treated with platinum-based chemotherapy showed a decreased renal function (CRCL <90 ml/min/1.73m2). Renal function before start of chemotherapy is an important predictor for renal function in the long-term. Further research in relation to treatment related collateral damage and strategies for prevention of cisplatin-induced nephrotoxicity is needed.
Introduction- Oxygen is one of the most widely used drugs and is applied across the wide range of specialities. Liberal use of oxygen to reassure oxygen delivery has become standard treatment in resuscitation: in the ambulance, the emergency department (ED) and the intensive care unit (ICU). Today, most health care professionals do not adjust the amount of oxygen given when patients reach a saturation of 100% or a PaO2 which exceeds the normal range, resulting in hyperoxia. Because oxygen is a vital element, toxicity is not immediately obvious, but there is increasing evidence for the toxic effects of hyperoxia. Because of these potential harmful effects of hyperoxia it seems justified to aim for normoxia when giving oxygen therapy. Objective- This study aims to evaluate whether it is feasible to aim for normoxia when giving oxygen therapy to critically ill patients at the ED. Material and methods- This study was a prospective cohort study and was performed at the ED of the University Medical Center Groningen (UMCG). A protocol was developed, aiming for normoxia: PaO2 9,5-13,5 kPa or a corresponding oxygen saturation 94-98%. Hyperoxia was defined as PaO2 > 13.5 kPa or SaO2 > 98%, and hypoxia as PaO2 < 9.5 kPa or SaO2 < 94%. During a 14 week period all patients >18 years admitted to the ED that were registered for cardiology, internal medicine, emergency medicine and pulmonology requiring oxygen therapy (according to the judgement of the ambulance nurse, ED nurse or ED physician) were included. Results- During the study period the protocol was followed and normoxia was obtained in 140 of the 162 study patients (86%). Patients in which the protocol was not successful were mostly severe COPD (GOLD III/IV) patients (P<0.001) and patients with a COPD exacerbation (P= 0.03). Furthermore we found that in patients arriving with prehospital oxygen the protocol was more often not followed. Among the patients who received prehospital oxygen, patients arriving with a NRM (non-rebreather mask) were more often hyperoxic (P <0.001) on arrival at the ED compared to patients arriving with oxygen via a nasal cannula. Conclusion- This study showed that it is feasible to titrate oxygen therapy to normoxia at the ED. These study results will be used for further research assessing the feasibility of normoxia and its potential beneficial effects compared to hyper- or hypoxia in ED patients.
Endometrial clear cell carcinoma (CCC) and mixed endometrioid carcinoma with a clear
cell component (EEC-CC) are rare forms of endometrial carcinoma (EC). Traditionally,
these tumors are classified and treated as high grade tumors. However, just a few studies
have identified clinical outcome for patients with pure CCCs and little is known
about the overall survival of the mixed carcinomas. Also, the predictive value of pipelle
in subtyping these tumors has not yet been determined. Lastly, determining an immunoprofile
of these tumors could bring new insights in the pathogenesis of these tumors
and be of potential diagnostic aid.
We selected and revised 51 pure CCCs and 28 mixed EEC-CC cases diagnosed since 1980
in the UMCG and Isala Zwolle. Clinical outcome of these patients were compared to each
other. We also selected these patients for determining the positive predictive value of
pipelle compared to the definitive diagnosis on hysterectomy. Immunohistochemical
staining for ER, PR, PTEN, p53, HNF1-β, Napsin A, AMACR, p16 and MMR, which are
common markers used for CCC and endometrioid carcinoma, were performed on all
pure CCC and both components of the mixed carcinomas to obtain an immunoprofile of
We found an overall 5-year survival rate of 64% for CCC, compared to 68% for mixed
EEC-CC, which was not statistically significant. The positive predictive value of pipelle
for detecting a pure CCC is 100%, compared to 50% for a mixed EEC-CCC.
We found the immunophenotype of ER– and PR– (71.8-95.2% resp. 87.5-92.9%),
HNF1-β+ (61.9-91.7%) to be most common in all pure CCC cases. Loss of PTEN expression,
a p53 mutation and positive Napsin A was present in about 50% of all CCC and
AMACR immunoreactivity was present in 33%. For mixed carcinomas ER, PR and HNF1-
β expression significantly differed in expression between the endometrioid and clear
cell component. The clear cell component of the mixed tumor did show a significant
lower expression for HNF1-β and Napsin A compared to a pure CCC. Microsatellite instability
for MSH2/MSH6 was also significantly higher for mixed carcinomas compared to
The outcome of mixed carcinoma is not significantly different from a pure CCC, despite
the presence of a low-grade endometrioid component. Also, pipelle is highly predictive
for detecting a pure CCC, while correctly diagnosing just half of all mixed carcinomas.
An immunoprofile of loss of ER, PR and positive HNF1-β was most common in CCC of
our study. Furthermore, the immunoprofile of the CC component in mixed EEC-CC is
intermediate between pure CCC and EEC, suggesting a common pre-existing endometrioid
lesion from which the clear cell component originates.
Background: Sepsis is a major public health problem with a high level of mortality. The initial treatment of sepsis is based on the admission of intravenous fluid which significantly decreases the sepsis-related morbidity and mortality. However, only 50% of the patients are volume responders. When fluid therapy does not increase cardiac output (CO) or stroke volume (SV) it is useless and this overuse could be harmful, resulting in an increase of complications and mortality. This shows the importance of accurate admission of intravenous fluids to enhance the treatment of septic patients and minimalize the risks of excessive – or insufficient volume therapy. A method for noninvasive continue CO measurement is NICOM®, which uses bioreactance.
Objective: The purpose of this study is to evaluate the ability of the CO measured by NICOM® in combination with several standard measured clinical parameters to predict fluid responsiveness in septic patients. The use of clinical parameters appears to be insufficiently reliable for predicting fluid responsiveness.
Methods: During a period of 14 weeks, all patients admitted to the emergency department with suspected infection will be screened. If included, the first NICOM® measurements will be recorded 10 minutes after arrival (T0). Simultaneously, several hemodynamic – and metabolic parameters are registered. This process repeats for each admission of 500 ml fluids until discharge. A response to fluid therapy is defined as an increase in SV of at least 10% after fluid admission.
Results: In total, 38 septic patients who received fluid therapy were included, of which 66% were fluid responsive after infusion of 500 ml NaCl. After infusion of 1000 ml NaCl 81% of the study population were responder. Baseline characteristics including parameters measured by NICOM® and the clinical shockscore showed no differences between responders and non-responders and were not reliable for predicting fluid responsiveness in the total study population. However, the clinical shockscore was significantly higher in responders compared to non-responders in the severe septic patients. If patients were divided into responders/non-responders after 1000 ml fluid infusion, none of the non-responders showed a response after infusion of 1500 ml NaCl (NPV=100%, 95% CI=19,7-100).
Conclusion: Although NICOM® is able to monitor fluid responsiveness, it seems difficult to predict the response based on patient characteristics on baseline. For certain patients, infusion of 500 ml fluid therapy does not seem sufficient to induce an increase in SV. For this reason, the classification into responders and non-responders should be made after infusion of 1000 ml fluid therapy. If patients have not responded to fluid therapy at that time, the continuation of fluid infusion seems useless. The use of NICOM® could be beneficial in guiding fluid therapy, nevertheless further research is required to confirm this.
Background: In advanced Parkinson’s disease (PD), deep brain stimulation (DBS) is considered as an ultimate treatment; however inefficacy and side-effects remain a challenge. A reliable, non-invasive neurophysiological biomarker could be valuable enabling the application of DBS in a highly selective way. Corticomuscular coherence (CMC) could be used as a potential biomarker. CMC is seen as a representation of the co-operation between brain areas and muscles in motor tasks and is present in PD symptoms of tremor (tremor frequency range) and akinesia-rigidity (beta range).
Aim: To test CMC, measured by electroencephalography (cortex) and electromyography (muscles), as a potential biomarker for improvement in tremor and akinesia-rigidity after DBS.
Methods: In this single center prospective cohort pilot study, five tremor-dominant and five akinetic-rigid PD DBS candidates of the University Medical Centre Groningen (UMCG) were included. In the akinetic-rigid PD group, beta CMC was measured during a flexion, pinching and resting task; symptoms were assessed by the MDS-UPDRS III upper body akinetic-rigid items. In the tremor-dominant PD group, tremor CMC was retrieved during a maximal tremor task; symptoms by use of a clinical tremor score and accelerometer. Change in CMC after DBS was tested and correlations were performed between CMC and symptom severity. Thereafter, correlations between change in CMC and improvement in symptoms; and pre-DBS CMC and improvement in symptoms were made.
Results: Tremor CMC decreased significantly after DBS (p=0.01) and significantly correlated with tremor severity (p<0.01). No relation between the decrease in tremor CMC and tremor reduction; and between pre-DBS CMC and tremor reduction was found. No significant increase in akinetic-rigid PD total beta CMC was detected after DBS and no relation with severity and improvement in akinesia-rigidity was seen. However, high beta CMC during flexion did correlate with severity (rs =-0.45; p<0.05), and improvement in akinesia-rigidity correlated with the percentage increase in high beta CMC and high beta CMC pre-DBS (rs =0.75, p=0.01; rs =-0.71, p=0.02).
Conclusion: Correlations between high beta CMC with symptom severity and clinical effect during flexion in the akinetic-rigid PD group were found; in the tremor-dominant PD group, CMC did decrease significantly and was associated with symptom severity. However, the beta CMC was insignificantly increased after DBS in the akinetic-rigid PD group and there were lack of correlations between tremor CMC and clinical effect in the tremor-dominant PD group. Further, due to the small sample size in this pilot study, utility of CMC as a potential biomarker cannot be recommended yet and further research on a larger scale is strongly advised.
Glioblastomas (GBMs) are the commonest and most malignant primary brain tumour. It is suggested that GBMs can arise from neural stem cells within the subventricular zone (SVZ). However, evidence demonstrating these cancer stem cells in GBM is lacking. This study aimed to identify the imaging characteristics of the SVZ and its relation to recurrent disease in patients with GBM by using multimodal imaging.
We included 99 primary GBM patients who underwent preoperative multimodal imaging. Follow-up data was available for 33 patients. Initial and recurrent tumours were classified into SVZ contacting and non-contacting GBMs. Diffusion and perfusion parameters were calculated in SVZ related and SVZ non-related regions.
Diffusion imaging showed signs of tumour infiltration in the SVZ with high FLAIR signal. Furthermore we found that over half of the patients with an initial SVZ non-contacting tumour recurred within the SVZ. These patients showed increased diffusion parameters in the SVZ compared to locally recurrent tumours on preoperative imaging.
Our diffusion parameters were able to show the presence of tumour cells within the SVZ, which supports the presence of a SVZ component in GBM. Preoperative evaluation of the SVZ with diffusion MRI was able to detect signs of tumour infiltration and can predict patterns of GBM recurrence within the SVZ.
Background and objective Neonatal sepsis is a severe disease in preterm infants that can
result in significant morbidity in this vulnerable patient group. Our aim was to identify and
assess the risk factors and incidence of neonatal sepsis in two different groups of preterm
infants (very preterm-and moderate to late preterm infants) in a level 2 neonatal ward.
Methods We conducted a retrospective cohort study in preterm infants with a gestational age
(GA) of <36weeks transferred to or born in our centre from 2009 to 2012. Sepsis was defined
as a positive blood culture and clinical symptoms, with early -and late onset sepsis defined as
onset of symptoms before 72 hours and after 72 hours of life, respectively. Univariate and
multivariate logistic analyses were performed.
Results We included 163 very preterm infants (GA<32weeks) and 434 moderate-to late
preterm infants (GA 32-36weeks). Neonatal sepsis was found in 6% (36/597) of preterm
infants. There was a significant association between the type of group a neonate belonged to
(according to GA) and whether or not sepsis was diagnosed (p < 0.002). The odds of sepsis
for neonates were 2.7 times higher if they were born with a GA <32 weeks (group A) than if
they were born with a GA 32- 36 weeks (group B). Early-onset sepsis (EOS) with group B
streptococcus occurred in one late preterm infant (0.7%) of 146 suspected episodes. Lateonset
sepsis (LOS) occurred in 35 preterm infants of a total of 90 suspected episodes (39%).
Coagulase-negative staphylococci was the most frequently pathogen isolated in LOS. Total
parenteral nutrition administration, vaginal spontaneous birth and gestational age were
significantly associated with LOS.
Conclusion This study shows a very low prevalence of EOS and LOS in both very preterm
and moderate preterm infants. Vaginal spontaneous birth was found to be a significant
protective factor for LOS. TPN administration (by central venous catheter, peripheral inserted
catheter), vaginal spontaneous birth and lower GA were found to be significant risk factors
for development of LOS.
The aim of this project was to investigate whether follicular helper T cells are present in the major salivary glands of primary Sjögren’s syndrome patients and to determine the effect of treatment with rituximab or abatacept on these cells. Furthermore, we analyzed local levels of IL21, a signature cytokine produced by Tfh-cells, before and after treatment. Tfh-cells defined by their expression of ICOS and CXCR5 were found in some, but not all patients analyzed. Also high numbers of IL21-positive cells were found in the parotid glands of all patients, and a decrease was seen in some patients after treatment with both rituximab and abatacept. Decreased expression of IL21 and CXCL13 was also seen at the mRNA level, suggesting a possible reduction in Tfh-cell activity and attraction of CXCR5+ cells into the salivary gland. Because of the small number of patients analyzed in this study, no statistically significant changes were yet detected. However, the results described here do suggest a possible local effect on Tfh-cells and other IL21-producing cells of both rituximab and abatacept in primary Sjögren’s syndrome. The presence of Tfh-cells and the high number of IL21-positive cells in the parotid glands also suggests that Tfh-cells are involved in the inflammatory process seen in pSS.
Introduction Diabetes Mellitus is a systemic disease having many adverse long-term effects on multiple organs. The incidence of both Types of Diabetes is vastly rising, affecting patients particularly in the Western World.
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and kidney failure worldwide, being the strongest mortality predictor in patients with diabetes. Recent data revealed that Toll-like receptor 4 (TLR4)-mediated inflammation is associated with initiation and progression of DN. We hypothesized that urokinase-type plasminogen activator receptor (uPAR) might serve as a co-receptor to TLR4 in diabetes-associated inflammation.
Methods Human Microvascular Endothelial Cells (HMEC-1) were stimulated with low and high concentration of glucose to simulate diabetes. Inflammatory markers were measured via PCR and ELISA. TLR4 and uPAR expression was measured via Western blot. The interaction of the two receptors was quantified by co-immunoprecipitation and immunocytochemistry. uPAR expression was downregulated using lentiviral cell infection and glucose-dependent signaling pathways were analyzed by Western blotting.
Results Inflammatory cytokines were up-regulated in HMEC-1stimulated with high glucose. TLR4 and uPAR expression was elevated when HMEC-1 were set under diabetic conditions. TLR4/uPAR interaction could be proven in glucose induced diabetic HMEC-1. Lentiviral downregulation of uPAR proved that uPAR has a functional involvement in cellular response to high glucose in endothelial cells which is probably linked to TLR4 signaling.
Discussion/Conclusion Data suggests that TLR4/uPAR interaction plays an important role in diabetes-associated inflammation. This interaction needs to be verified and established further by in vitro studies in primary cells as well as on an in vivo model in mice. TLR4/uPAR interaction could be blocked by means of peptide inhibitors, thus having a great therapeutic impact in Diabetes associated DN.
Introduction: In pediatric pulmonary arterial hypertension (PAH), RV failure is the main cause of death. Right ventricular-vascular coupling ratio (VVCR) is gaining interest as it encloses both contractility and afterload. Conventional determination of VVCR by catheterization (VVCRs) is invasive and frequently requires anesthesia. Therefore, the goal of this study was to compare the usefulness of noninvasively determined VVCR by cardiac magnetic resonance (CMR) (VVCRm) to VVCRs in pediatric PAH.
Hypothesis: We assessed two hypotheses: 1) VVCRm is a good estimate of VVCRs; and 2) both serve as good measures of disease severity and outcome.
Methods: Retrospectively, PAH patients who had catheterization and CMR within 90 days were included from two specialized PH centers. VVCR was defined as the end-systolic elastance/effective arterial elastance ratio. VVCRm as stroke volume/end-systolic volume ratio and VVCRs by single-beat method were compared using regression analysis and Bland-Altman plots. Both were correlated to disease severity (PVRi, mRAP, CI) and adverse outcome (death, lung transplantation, atrial septostomy and intravenous medication). The area under the receiver operating characteristic curve (AU-ROC), Kaplan-Meier curves and hazard ratios (HR) from Cox regression determined their value in predicting adverse outcome.
Results: In the 31 patients included (17 from CHC and 14 from UMCG), median age was 14 years (0.3 – 23) and median PVRi was 7.6 WU × m2 (2.1 – 32). VVCRm and VVCRs were strongly correlated (r = 0.78, p < 0.001) with a mean difference of 0.2 and 95% of the differences between -0.3 and 0.7. Both had comparable significant correlations with disease severity and adverse outcome. Also, both VVCRm and VVCRs were shown to be of good prognostic value with AU-ROCs of respectively 0.84 and 0.90 and HRs (95%-CI) of 0.82 (0.70 – 0.96) and 0.69 (0.53 – 0.90).
Conclusion: In line with previous research, the results of this study indicate that VVCRm and VVCRs are comparable in pediatric PAH and are both good predictors of outcome. The characteristic disease progression is clearly seen in VVCRm, but its clinical use has to be defined by further research.
Benno Haarman: The dysregulated brain – A psychoimmunological approach to bipolar disorder Bij mensen met een bipolaire stoornis is het …
Mark-Jan Ploegstra: Prognostic factors, treatment goals and clinical endpoints in pediatric pulmonary arterial hypertension Het is mogelijk om met …
Introductie: Het ‘International Network on Cancer, Infertility and Pregnancy’ (INCIP) publiceerde recentelijk de onderzoeksresultaten van de lange termijn gevolgen voor het kind van oncologische behandeling gedurende de zwangerschap.1 Op het vlak van algehele gezondheid, cognitief vermogen en cardiale ontwikkeling werd geen verschil gezien met de algemene populatie.1,2 Wat bij zwangeren met kanker echter opviel was dat er relatief meer small for gestational age (SGA) kinderen geboren werden (gedefinieerd als geboortegewicht
Objective: To investigate the association between size, number and location of cerebellar hemorrhage (CBH) and neurodevelopmental outcome in very preterm infants, diagnosed with either isolated CBH or combined CBH and supratentorial brain lesions. Secondly, the aim is to investigate associations between perinatal, postnatal and maternal factors and CBH.
Methods: A cohort of preterm infants (≤ 34 weeks) born between 2006 and April 2016, and admitted to one of the three participating Dutch NICUs, was generated. Data (perinatal factors, neuro-imaging and follow-up at 2 years) were retrospectively collected. MRI and/or cranial ultrasound scans were reassessed to determine the exact size, number and location of CBH and the presence of supratentorial injury. Infants were divided between two groups: punctate CBH (≤ 4 mm) or major CBH (> 4 mm). The composite outcome score for neurodevelopmental outcome was defined by the result of the Bayley Scale of infant Developmental (BSID) test and the neurological examination.
Results: Data of 111 preterm infants were analyzed. Of 56 infants the composite outcome score could be obtained. Seven out of 14 infants (50%) with major CBH and 17 out of 42 (40%) with punctate CBH had an abnormal composite outcome score. Laterality of CBH and vermian lesions were not significant associated with an abnormal composite outcome score. HFO ventilation ventilation and supratentorial injury were independent risk factors for an abnormal composite outcome score. Independent risk factors for the occurrence of major CBH were gestational age (correlated with birth weight), forceps or ventouse delivery, severe thrombocytopenia (with a platelet count < 50) and maternal age.
Conclusion: Our results show that major CBH is associated with an unfavorable outcome when compared to punctate CBH. No evident association between the size and location of CBH and outcome was found. However, the study population was too small to draw firm conclusions.
Gert Jan Pelgrim: Quantitative CT myocardial perfusion Ziekte aan de kransslagaders kan goed aangetoond worden met CT-scans. Dat laat Gert Jan …
Rob Wanders: Symptoms and depression: it’s time to break up Depressieve patiënten verschillen sterk van elkaar, zowel in de klachten die ze hebben …
Background and Objectives The Dutch Ministry of Health, Welfare and Sport is expected to take a decision on short term on the provision of Non-Invasive Prenatal Testing (NIPT) in the 10th week for all pregnancies. Herewith the current combined testing in the first trimester, with the Nuchal Translucency (NT) measurement as part, may completely disappear. However, it is confirmed that the predictive value of increased NT goes further than only diagnosing Trisomy 13, 18 and 21. The aim of this study is to identify on a national level what exactly the added value of NT measurement is, by discovering how many and which abnormalities can be detected by an NT measurement. That way, it can be mapped out which consequences the disappearance of combined testing will have; in other words which abnormalities might be delayed or not at all be diagnosed. Methods From the databases of four academic hospitals 16003 pregnancies were selected, whereby combined testing was performed in the first trimester of the pregnancy during the period 01-01-2010 up to and including 31-12-2015. Pre- and postnatal information, with emphasis on results of karyotyping, advanced ultrasound examination, post-mortem results and consultations by the clinical geneticist, was retrospectively collected and analyzed of all pregnancies with an increased NT (>95th percentile). Results 1390 fetuses (8.7%) had an increased NT; nearly half of them had an abnormality. 535 were diagnosed with Trisomy 13,18 or 21 and thus were potentially detectable by NIPT. 271 had a structural, genetic or rare chromosomal abnormality which was not detectable by NIPT. If NIPT will replace combined testing as screening method in the first trimester of the pregnancy, the consequence will be that the opportunity of early warning and diagnosing will be missed for these abnormalities. Conclusion Ideally both (screening)tests should be used in parallel. That way Trisomy 13, 18 and 21 can be diagnosed with high sensitivity and specificity and invasive procedures are less needed. On the other hand, using the NT measurement, adequate counseling and early diagnosis of severe abnormities can be accomplished, such preventing unpleasant surprises at the 20th week of pregnancy. Also in case of severe anomalies an earlier pregnancy termination is less traumatic for the mother. In addition, the missed cases of mainly Trisomy 13 and 18, where NIPT is less accurate, and where the NT is often thickened, yet can be diagnosed early.
Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents.
This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression and anxiety were measured using validated short form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed and regression models were used to identify determinants of sleep quality.
Our study included160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p=0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p=0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6.
Both vedolizumab and anti-TNF biologic therapy was associated with improvement in sleep and mood quality in IBD.