Much research into Placenta Accreta Spectrum (PAS) has focussed on the associated maternal morbidity and mortality. However, mothers' and fathers' lived experiences of the aftermath of a diagnosis of ...PAS up to the birth and beyond has received little attention. Therefore, the aim of this study was to increase our understanding of the psychological consequences of PAS on women and their partners during pregnancy, up to and including the birth.
In-depth interviews were conducted with 29 participants; 6 couples were interviewed together (n = 12), 6 couples were interviewed separately (n = 12), and 5 women were interviewed without their partner. Data from the antenatal and intrapartum periods are presented. Couples were eligible for inclusion if they had a diagnosis of PAS within the previous 5 years. An Interpretative Phenomenological Analysis approach was used to gather and analyse data. Virtual interviews were conducted over a 3-month period from February to April 2021.
Themes emerged relating to two distinct timepoints, the antenatal period and birth. The antenatal period had two main themes: the first antenatal main theme was "Living with PAS", which had two sub-themes: "Lack of knowledge of PAS" and "Experiences of varied approaches to care". The second antenatal main theme was "Coping with uncertainty", which had two sub-themes of "Getting on with it", and "Emotional toll". Relating to birth, two main themes emerged. The first main theme was "A traumatic experience", with three sub-themes of "Saying goodbye", "Experiencing trauma" and the "Witnessing of trauma" (by fathers). The second main theme which emerged was "Feeling safe in the hands of experts", with two subthemes of "Safety in expert team" and "Relief at surviving".
This study highlights the significant psychological consequences a diagnosis of PAS has on mothers and fathers, how they try to come to terms with the diagnosis and the experience of a traumatic birth, and how management within a specialist team can alleviate some of these fears.
The objective of this cross-sectional study was to reevaluate the prevalence of digital dermatitis (DD) and associated risk factors in The Netherlands. Between May 2002 and December 2003, information ...about the presence or absence of DD lesions and other claw disorders on the hind claws of dairy cows in The Netherlands was collected by 20 hoof trimmers during trimming of all dairy cows in 383 herds. A questionnaire was used to acquire information regarding management and housing. Additional information, such as parity, breed, and stage of lactation of the cows, was provided by the Dutch Herd Book Organization. Digital dermatitis was present in 21.2% (SE=0.3) of the study population (n=22,454 cows). The herd prevalence varied from 0% (9.1% of the herds) to 83.0%. Most common was herd prevalence between 5 and 10%. The Holstein-Friesian breed was at higher risk for DD odds ratio (OR)=1.7 than was the Meuse Rhine IJssel breed (dual purpose breed). The risk for DD decreased with increasing parity. Cows at the peak of their lactation (30 to 60 d in milk) and in the third parity had higher odds for DD in comparison with cows that were later than 60 DIM. The presence of other claw disorders, such as interdigital dermatitis/heel horn erosion (IDHE), interdigital hyperplasia (HYP), and interdigital phlegmon, appeared to be predisposing for DD. Based on estimation of the population-attributable fraction, it was concluded that if IDHE, HYP, and interdigital phlegmon were not present among the study population, respectively, 32.2, 9.0, and 1.1% of the DD cases could have been prevented. The risk for DD slightly decreased when cows affected by IDHE had access to pasture. Because of the interrelation between infectious claw disorders, an effective intervention strategy against DD should focus on an integrated approach to the control of all infectious claw diseases. Cows trimmed >12 mo before the study (during regular trimming of the entire herd) were at lower risk for DD than were cows that were trimmed at shorter intervals. Animals that had >8h of access to pasture were at higher risk for DD (OR=1.6) compared with no access to pasture. Finally, cows in small-sized herds (<45 cows) affected with HYP were at lower risk (OR=0.6) for DD than were cows affected with HYP in medium- and large-sized herds (60 to 85 cows per herd).
Abstract Aim of the study Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical ...tumour and treatment factors in hereditary BC is insufficiently known. Methods We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980–2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing ⩾2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. Results We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. Conclusions Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.
Many laboratories use enzyme immunoassays (EIAs) for the diagnosis of
Clostridium difficile
infection (CDI). More recently, polymerase chain reaction (PCR)-based diagnosis has been described as a ...sensitive test. Real-time PCR for the detection of
C. difficile
toxin A and B genes was evaluated. A prospective evaluation was performed on stool samples from 150 hospitalized adult patients and 141 healthy volunteers. PCR was compared to toxigenic culture (TC), direct cytotoxicity test (CTT), ImmunoCard® Toxin A and B (Meridian Bioscience), and enzyme-linked immunosorbent assay (ELISA) (Vidas). The results were correlated with clinical data using a standardized questionnaire. The diagnostic yield of the PCR was further evaluated after implementation. Using toxigenic culture as the gold standard, the sensitivity and specificity of PCR were 100 and 99.2%, respectively. Patients were categorized as follows: TC/PCR-positive (
n
= 17) and negative TC (
n
= 133). The differences in these groups were more frequent use of antibiotics and leukocytosis (
p
< 0.05). The diagnostic yield of PCR was evaluated during a period of 6 months and showed an increase of positive patients by 50%. PCR for the detection of toxigenic
C. difficile
has a high sensitivity and can rule out CDI, but cannot differentiate CDI from asymptomatic carriage. Clinicians should be aware of this in order to prevent inappropriate treatment and delay of other diagnostics.
Does testosterone use in females affect reproductive potential, particularly with regard to the production of fertilizable gametes?
Testosterone (T) injections given to post-pubertal female mice ...caused virilization and although the ovaries were smaller than controls they were still responsive and produced fertilizable eggs when superovulated.
Studies to examine the effects of testosterone on reproductive potential in transgender males are lacking. Recently, a model was developed that simulates many aspects of testosterone use in transgender males in order to look at reproductive effects of testosterone in female mice. This study found masculinizing effects on the mice but did not find significant deficits on the number of ovarian follicles; however, effects of testosterone use on ovarian stimulation and fertilizability of oocytes were not investigated.
A total of 66, 6-week-old Hsd:NSA (CF-1) female mice and six Hsd:ICR (CD-1) male mice were used for this study. Mice were injected s.c. with 400 µg T or sesame oil once a week for 6 weeks and were either killed 1 week after the sixth injection (active exposure group), or 6-7 weeks after the final T injection (washout group).
Both active exposure and washout groups were further subdivided into three groups: unstimulated, equine CG (eCG)-stimulated or eCG/hCG-stimulated. eCG-stimulated mice were killed 44-48 h after eCG injection. eCG/hCG-stimulated mice were injected with eCG, followed 48 h later with hCG. Mice were killed ∼13-18 h after the hCG injection. Data collected included daily vaginal cytology, terminal testosterone levels, ovary weights and histology, number of oocytes/eggs collected in each group, and cleavage to the two-cell stage following IVF.
Testosterone-treated mice had testosterone levels elevated to the level of male mice and ceased cycling. Ovaries were significantly smaller in testosterone-treated mice, but they contained normal cohorts of follicles and responded to gonadotrophin stimulation by ovulating similar numbers of eggs as controls, that fertilized and cleaved in vitro.
Mice were treated for only 6 weeks, whereas many transgender men use testosterone for many years before considering biological children, and developmental competence was not assessed. Importantly, a mouse system may not perfectly simulate human reproductive physiology.
The current standard of care for transgender men who desire biological children is to cease testosterone therapy prior to ovarian stimulation, but the necessity for stopping testosterone is not known. Our model demonstrates that it is possible for testosterone-suppressed ovaries to respond to gonadotrophic stimulation by producing and ovulating fertilizable eggs, thereby obviating the need for testosterone cessation prior to ovarian stimulation. In time, these results may provide insights for future clinical trials of fertility treatment options for transgender men.
This study was funded by the Reproductive Endocrinology and Infertility fellowship program through UConn Health Graduate Medical Education (to C.B.B.). The authors have no competing interests.
N/A.
Placenta Accreta Spectrum is associated with significant clinical maternal morbidity and mortality, which has been extensively described in the literature. However, there is a dearth of research on ...the lived experiences of pregnant people and their support partners. The aim of this study is to describe living beyond a pregnancy and birth complicated by PAS for up to four years postpartum. Participants experiences inform the development of an integrated care pathway of family centered support interventions.
An Interpretative Phenomenological Analysis approach was applied to collect data through virtual interviews over a 3-month period from February to April 2021. Twenty-nine participants shared their stories; six people with a history of PAS and their support partners were interviewed together (n = 12 participants), six were interviewed separately (n = 12 participants), and five were interviewed without their partner. Pregnant people were eligible for inclusion if they had a diagnosis of PAS within the previous 5 years. This paper focuses on the postnatal period, with data from the antenatal and intrapartum periods described separately.
One superordinate theme "Living beyond PAS" emerged from interviews, with 6 subordinate themes as follows; "Living with a different body", "The impact on relationships", "Coping strategies", "Post-traumatic growth", "Challenges with normal care" and recommendations for "What needs to change". These themes informed the development of an integrated care pathway for pregnant people and their support partners to support them from diagnosis up to one year following the birth.
Parents described the challenges of the postnatal period in terms of the physical and emotional impact, and how some were able to make positive life changes in the aftermath of a traumatic event. An integrated care pathway of simple supportive interventions, based on participant recommendations, delivered as part of specialist multidisciplinary team care may assist pregnant people and their support partners in alleviating some of these challenges.
The objective of this medical record review study is to define the association between smoking and Sjӧgren's syndrome (SS) in a large rheumatoid arthritis (RA) cohort.
Electronic health records from ...a population-based cohort were screened for RA eligibility between 2005 and 2018. Inclusion criteria were age ≥ 18 years, two or more RA diagnoses, including two diagnoses by a rheumatologist, or positive rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibody. The independent variable, smoking status, was defined as never, current, or past. The outcome, SS, was defined by two or more ICD-9 codes. Multivariable logistic regression was performed to determine odds ratios (ORs) of SS adjusted for age, sex, and race.
Among 1861 patients with RA identified for cohort inclusion, 1296 had a reported smoking status. Current smokers were younger and less likely to be female than never smokers. The adjusted OR of current compared to never smokers was negatively associated with SS OR 0.20, 95% confidence interval (CI) 0.06-0.65. Female sex and age were associated with SS (OR 2.70, 95% CI 1.18-6.14; OR 3.75, 95% CI 1.23-11.4).
We report that RA patients who currently smoke had 80% lower odds of SS. Age had a 3.7-fold association and female sex a 2.7-fold association with SS among RA patients. Our data suggest a negative correlation between current smoking and prevalent SS among RA patients. Prospective studies examining pack-year relationships or smoking cessation could further examine risk reduction and causality to follow-up our cross-sectional observational study.
Trilobites, extinct arthropods that dominated the faunas of the Palaeozoic, since their appearance c 523 million years ago, were equipped with elaborate compound eyes. While most of them possessed ...apposition compound eyes (in trilobites called holochroal eyes), comparable to the compound eyes of many diurnal crustaceans and insects living today, trilobites of the suborder Phacopina developed atypical large eyes with wide lenses and wide interspaces in between (schizochroal eyes). Here, we show that these compound eyes are highly sophisticated systems-hyper-compound eyes hiding an individual compound eye below each of the big lenses. Thus, each of the phacopid compound eyes comprises several tens, in cases even hundreds of small compound eye systems composing a single visual surface. We discuss their development, phylogenetic position of this hyper-compound eye, and its neuronal infrastructure. A hyper-compound eye in this form is unique in the animal realm.
Background: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the ...classical tumour and treatment factors is unclear in BRCA1-associated BC. Patients and methods: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers. Results: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HRmult 0.7; P = 0.24), DDFS (HRmult 1.2; P = 0.37) or BC-specific survival (HRmult 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HRmult 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen. Conclusions: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.
Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS ...could serve as an effective treatment for patients with MICCH.
The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks’ baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25–48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21–24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631).
Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21–24, a median change of –5·21 (–11·18 to –0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21–24 weeks (median change from baseline –4·08, –11·92 to –0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; –6·50, –10·83 to –0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21–24 was –2·42 (95% CI –5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage.
In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action.
The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.
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