Challenges faced by children diagnosed with a rare disease or complex condition and their family members are often characterized by disease-specific complexities, such as a prolonged diagnostic ...process, an uncertain prognosis, and the absence of curative treatment. The psychological burden of living with a rare disease or complex condition is often understudied and may present overarching concepts that shape the general experience of having been diagnosed with a rare condition. The present study examines common needs from a comprehensive perspective combining relevant aspects from the rare disease literature in a theoretical perspective from pediatric psychology, such as a family-centred, developmental and interdisciplinary approach. An exploratory study was designed among parents from children with a rare disease or complex condition in an Integrated University Children's Hospital in the Netherlands. Semi-structured interviews were conducted with open-ended questions based around the experience of having a child diagnosed with a rare condition, such as the psychosocial impact on the child and it's development, the impact on the family, and how provided care was experienced.
Twelve interviews were analysed with a thematic content analysis to identify common needs. Eight themes followed from the analysis and uncovered the need for (1) family-focused care, (2) coping with uncertainty, (3) empathic communication, (4) practical support, (5) information, (6) psychological support, (7) interdisciplinary care, and (8) social support.
The results from our study provide directions for research and health care to support young patients with a rare disease or complex condition and their families. Moreover, our results demonstrated that there are overarching concepts across different rare diseases that may be optimally supported with interdisciplinary care.
Abstract Context Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. Objective To systematically ...investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. Evidence acquisition A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Evidence synthesis Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Conclusions Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. Patient summary We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study design is required to improve clinical translation of tissue engineering technologies.
In 2017, the European Commission launched 24 European Reference Networks (ERNs). ERN eUROGEN is the network for urorectogenital diseases and complex conditions, and started with 29 full member ...healthcare providers (HCPs) in 11 countries. It then covered 19 different disease areas distributed over three workstreams (WSs).
To provide an overview and identify challenges in data collection at European level of the ERN eUROGEN patient population treated by HCPs in the network.
A retrospective cohort study was conducted of the 29 HCPs who were full members between 2013 and 2019.
Data were extracted from the original HCP applications and the ERN continuous monitoring system. Patient volumes, new patient numbers, and procedures were compared between different WSs, countries, and HCPs. Discrepancies between monitoring and application data were identified.
Between 2013 and 2019, 122 040 patients required long-term care within the 29 HCPs. The volume of patients treated and procedures undertaken per year increased over time. Large discrepancies were found between patient numbers contained in the application forms and those reported in the continuous monitoring system (0–1357% deviation).
Patient numbers and procedures increased across ERN eUROGEN HCPs. Reliable data extraction appeared challenging, illustrated by the patient volume discrepancies between application forms and the continuous monitoring data. Improved disease definitions, re-evaluation of affiliated HCPs, and valid data extraction are needed for future improvements.
We analysed the patient population with rare urorectogenital diseases or complex conditions within the ERN eUROGEN network between 2013 and 2019. Clinical activity was found to increase, but differences in patient numbers were evident between healthcare providers. In order to acquire valid patient numbers, both improved definitions of diagnostic codes and greater insight into the data-gathering process are required.
For patients with a rare or complex urological anomaly and their care takers, ERN eUROGEN aims to improve knowledge exchange and expertise sharing, to optimise care pathways and innovate cure potential for all rare urorectogenital diseases and complex conditions in the European Union. The data show that ERN eUROGEN’s healthcare providers and expert multidisciplinary teams are treating an increasing number of patients and performing an increasing number of complex surgical procedures.
Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias ...cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1,812 controls from Denmark, the Netherlands and Sweden, 18 genomic regions showed independent association with P < 5 × 10(-8). Together, these loci explain 9% of the liability to developing this condition. Several of the identified regions harbor genes with key roles in embryonic development (including HOXA4, IRX5, IRX6 and EYA1). Subsequent pathway analysis with GRAIL and DEPICT provided additional insight into possible genetic mechanisms causing hypospadias.
What's known on the subject? and What does the study add?
The various phenotypes of hypospadias may result from disturbances of dissimilar embryonic processes in different time windows, suggesting ...aetiological heterogeneity; however, only a few studies have investigated the risk factors for the different hypospadias phenotypes.
The study confirmed that genetic predisposition possibly plays a role in anterior and middle hypospadias, as shown by the large effect estimates for familial occurrence of these forms of hypospadias. By contrast, the posterior phenotype was more often associated with pregnancy‐related factors, such as primiparity, preterm delivery, and being small for gestational age. New findings were that hormone‐containing contraceptive use after conception increased the risk of middle and posterior hypospadias, while multiple pregnancies were associated with the posterior form in particular.
Objective
To identify specific risk factors for different phenotypes of hypospadias that may arise as a result of dissimilar embryonic processes in different time windows.
Patients and Methods
A total of 405 hypospadias cases and 627 male controls were included in a Dutch case–control study.
Medical records of cases were reviewed to determine the anatomical location of the urethral opening, while demographic, lifestyle and pregnancy‐related risk factor data were obtained from self‐administered questionnaires.
Multivariable and multinomial logistic regression analyses were used to calculate effect estimates for the group containing all cases of hypospadias and for the different hypospadias phenotypes.
Results
Cases were subdivided into anterior (glandular and coronal; 59%), middle (penile; 29%) and posterior (penoscrotal, scrotal and perineal; 12%) hypospadias.
Being a twin/triplet, primiparity, preterm delivery, and being small for gestational age were associated with hypospadias, particularly in posterior cases.
Family history of hypospadias increased the risk of hypospadias, an effect that seemed to be more predominant in anterior and middle forms.
Maternal obesity seemed to increase the risk of hypospadias in general, and hormone‐containing contraceptive use during pregnancy especially increased the risk of middle and posterior hypospadias.
Conclusions
Our study provides some indications for aetiological heterogeneity of hypospadias, separating anterior and middle phenotypes from posterior hypospadias.
Future research should continue to try to establish which specific risk factors and mechanisms may differ according to hypospadias phenotype.
Abstract Congenital malformations or injuries of the urethra can be treated using existing autologous tissue, but these procedures are sometimes associated with severe complications. Therefore, ...tissue engineering may be advantageous for generating urethral grafts. We evaluated engineered high-density collagen gel tubes as urethral grafts in 16 male New Zealand white rabbits. The constructs were either acellular or seeded with autologous smooth muscle cells, isolated from an open bladder biopsy. After the formation of a urethral defect by excision, the tissue-engineered grafts were interposed between the remaining urethral ends. No catheter was placed postoperatively. The animals were evaluated at 1 or 3 months by contrast urethrography and histological examination. Comparing the graft caliber to the control urethra at 3 months, a larger caliber was found in the cell-seeded grafts (96.6% of the normal caliber) than in the acellular grafts (42.3%). Histology of acellular and cell-seeded grafts did not show any sign of inflammation, and spontaneous regrowth of urothelium could be demonstrated in all grafts. Urethral fistulae, sometimes associated with stenosis, were observed, which might be prevented by urethral catheter application. High-density collagen gel tubes may be clinically useful as an effective treatment of congenital and acquired urethral pathologies.
Children with a solitary functioning kidney (SFK) have an increased risk of kidney injury. The exact risk of and risk factors for kidney injury remain unknown, which impedes personalized care. Here, ...we recruited a nationwide multicenter cohort of 944 patients with SFK to get more insight into this by consenting patients born in 1993-2020 and diagnosed with congenital or acquired SFK before adulthood. The median follow-up was 12.8 years and four indications of kidney injury were studied: urine protein-creatinine ratios, blood pressure, estimated glomerular filtration rate and use of anti-hypertensive/proteinuric medication. For each indicator except medication use, separate cut-off values for any injury and severe injury were used. Survival analyses indicated that at 18 years of age, any or severe kidney injury were present in 75% and 39% of patients with congenital SFK, respectively. Risk factors for kidney injury included kidney agenesis as cause of the SFK, anomalies in the SFK, and high body mass index at last follow-up. Kidney agenesis and being overweight were specifically associated with proteinuria and high blood pressure, whereas anomalies in the SFK were associated with reduced estimated glomerular filtration rates. The high prevalence of kidney injury in patients with SFK emphasizes the need for long-term follow-up, in which lifestyle is an important topic to address. More research into the etiological role of risk factors will help to translate our findings into individualized care strategies. Thus, our study shows that a significant proportion of children with SFK will develop kidney injury over time.
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Tissue Engineering (TE) approaches are needed to advance the field of reconstructive urology. We indicate that regeneration of ureteral tissue and the formation of a urinary diversion using TE ...approaches are possible, although it is currently very time-consuming and complex to achieve well-developed neotissue. Faster regeneration approaches using novel scaffolds are desirable. The findings of this review may help to develop smart hybrid scaffolds and enhance the design of future studies, which may ultimately lead to improved care for patients with ureteral defects as well as to curb complications associated with urinary diversion.
This study aimed at evaluating how transition of care is currently being organized in the European Reference Networks (ERNs) health care providers (HCPs) in pediatric areas and in the Anorectal ...Malformation Network (ARM-Net) Consortium hospitals. An online questionnaire was sent to a total of 80 surgeons, members of or affiliated members of three networks: ARM-Net Consortium, ERN eUROGEN, and ERN ERNICA. Complete information were obtained for 45 HCPs, most of which deal with transition and still see a few adult patients (ca. 10%). Gynecological, gastroenterological, urological, colorectal, and continence issues were the major problems described by adult patients to their physicians, and in line with these prevalent complaints, they are referred to the appropriate adult specialists. Forty percent of patients complain about sexual and fertility problems, but the percentage of andrologists and sexologists involved in the caring of adult patients with ARM/Hirschsprung's disease is low, just above 10.9%. Most hospitals deal with transition, but three basic criteria (i.e., presence of: 1 an official written transitional program, 2 a transitional coordinator, and 3 written information on transition to be handled to patients) are jointly met only by six HCPs. According to the responders, the most important issue requiring improvement is the lack of interest and of specific preparation by adult specialists. The overall results of this exploratory survey confirm the need for the development of comprehensive programs for transition in these rare and complex diseases, and identify the hospitals that, in collaboration with the networks, could share best practices in organizing structured transitional pathways and well follow-ups.
Purpose Hypospadias is a common congenital malformation of the male external genitalia. Association studies for single nucleotide polymorphisms in genes encoding steroid 5alpha-reductase, estrogen ...receptors 1 and 2, and activating transcription factor 3 have been equivocal. We examined whether nonreplication of findings for 4 single nucleotide polymorphisms in these genes could be due to interaction with environmental exposures. Materials and Methods We genotyped 712 Dutch hypospadias case-parent triads for the 4 single nucleotide polymorphisms, used questionnaire information to determine exposures and performed association tests using the log-linear approach. We studied gene-environment interactions for the 4 single nucleotide polymorphisms with exposure to estrogens, cytokines or cigarette smoke, multiple birth, being born small for gestational age, maternal hypertension or preeclampsia, high body mass index or primiparity. In addition, the presence of maternal genetic and parent of origin effects was tested. Results Gene-environment interactions were identified for rs523349 in SRD5A2 with estrogen exposure and maternal hypertension or preeclampsia, as well as for rs11119982 in ATF3 with exposure to cytokines. Both single nucleotide polymorphisms seemed to influence hypospadias risk only in exposed cases. For rs6932902 in ESR1 only maternally derived alleles appeared to increase hypospadias risk in offspring. Conclusions Interactions between genetic and environmental factors may help to explain nonreplication in genetic studies of hypospadias.
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