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Primary hyperoxaluria type 1 displays a heterogeneous phenotype, likely to be affected by genetic and non-genetic factors, including timeliness of diagnosis and quality of care. As previous genotype-phenotype studies were hampered by limited patient numbers the European OxalEurope Consortium was constituted. This preliminary retrospective report is based on 526 patients of which 410 have the AGXT genotype defined. We grouped mutations by the predicted effect as null, missense leading to mistargeting (G170R), and other missense, and analyzed their phenotypic correlations. Median age of end-stage renal disease increased from 9.9 for 88 homozygous null patients, 11.5 for 42 heterozygous null/missense, 16.9 for 116 homozygous missense patients, 25.1 for 61 G170R/null patients, 31.2 for 32 G170R/missense patients, and 33.9 years for 71 homozygous G170R patients. The outcome of some recurrent missense mutations (p.I244T, p.F152I, p.M195R, p.D201E, p.S81L, p.R36C) and an unprecedented number of G170R homozygotes is described in detail. Diagnosis is still delayed and actions aimed at increasing awareness of primary hyperoxaluria type 1 are recommended. Thus, in addition to G170R, other causative mutations are associated with later onset of end-stage renal disease. The OxalEurope registry will provide necessary tools for characterizing those genetic and non-genetic factors through a combination of genetic, functional, and biostatistical approaches.

Clinical implications of mutation analysis in primary hyperoxaluria type 1. Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity. Although over 50 disease-causing mutations have been identified, the relationship between genotype and clinical outcome remains unclear. The aim of this study was to determine this association in order to find clues for improvement of patient care. AGXT mutation analysis and assessment of biochemical characteristics and clinical outcome were performed on patients from a Dutch PH1 cohort. Thirty-three of a cohort of 57 PH1 patients, identified in The Netherlands over a period of 30 years, were analyzed. Ten different mutations were found. The most common mutations were the Gly170Arg, Phe152Ile, and the 33insC mutations, with an allele frequency of 43%, 19%, and 15%, respectively. Homozygous Gly170Arg and Phe152Ile mutations were associated with pyridoxine responsiveness and a preserved renal function over time when treatment was timely initiated. All patients homozygous for the 33insC mutation had end-stage renal disease (ESRD) before the first year of age. In two unrelated patients, a new Val336Asp mutation was found coupled with the Gly170Arg mutation on the minor allele. We also found 3 patients homozygous for a novel Gly82Arg mutation with adverse outcome in 2 of them. Early detection of Gly170Arg and Phe152Ile mutations in PH1 has important clinical implications because of their association with pyridoxine responsiveness and clinical outcome. The association of a homozygous 33insC mutation with severe infantile ESRD, resulting in early deaths in 2 out of 3 cases, warrants a choice for prenatal diagnostics in affected families.

Purpose The added value of measuring patient-reported outcomes (PROs) for delivering patient-centered care and assessment of healthcare quality is increasingly evident. However, healthcare system wide data collection initiatives are hampered by the proliferation of patient-reported outcome measures (PROMs) and conflicting data collection standards. As part of a national initiative of the Dutch Ministry of Health, Welfare and Sport we developed a consensus-based standard set of generic PROs and PROMs to be implemented across Dutch medical specialist care. Methods A working group of mandated representatives of umbrella organizations involved in Dutch medical specialist care, together with PROM experts and patient organizations worked through a structured, consensus-driven co-creation process. This included literature reviews, online expert and working group meetings, and feedback from national patient- and umbrella organizations. The ‘PROM-cycle’ methodology was used to select feasible, valid, and reliable PROMs to obtain domain scores for each of the PROs included in the set. Results Eight PROs across different domains of health were ultimately endorsed: symptoms (pain & fatigue), functioning (physical, social/participation, mental [anxiety & depression]), and overarching (quality of life & perceived overall health). A limited number of generic PROMs was endorsed. PROMIS short forms were selected as the preferred instruments for all PROs. Several recommendations were formulated to facilitate healthcare system level adoption and implementation of the standard set. Conclusions We developed a consensus-based standard set of Generic PROMs and a set of recommendations to facilitate healthcare system wide implementation across Dutch medical specialist care.

Although children wish to be included in their own healthcare, they recognize a gap between their right to be heard and their ability to become involved. Despite adaptation of medical consultation styles which suit a more patient-centered approach, data on the current state of child participation in clinical encounters are missing. We aimed to assess actual child participation in a Dutch pediatric clinic. Children aged 4–18 years visiting a pediatric outpatient clinic for consultation after general practitioner’s referral were included. Sixteen consultations of six pediatricians were recorded and transcribed verbatim. Quantitative measurement included word count and speech turn; conversation analysis with qualitative appraisal provided data on participatory behavior. Quantitative child participation equaled parent participation in turns (28% vs 29%, respectively), but remained limited in words (relative contribution 11% for child, 23% for parent and 66% for pediatrician). Children spoke on average six words per speech turn. Child age correlated positively with participation in words ( p  = 0.022, r  = 0.566) and turns ( p  =  < 0.001, r  = 0.746). Children were mostly involved during social history taking, introduction, and physical examination but did not actively speak during the decision-making process. Children took an active role by instigating talks. Qualitative facilitators included appropriate language and verbal or non-verbal child allocated turns. Adults involved children by asking them questions and verifying their opinions or plans with the child. Teenagers participated most during the entire consultation, while younger children were more likely to lose their focus by the end of the conversation. Conclusion : Despite increased turn taking, children’s verbal participation remains low in pediatric consultations. If pediatricians and parents maintain a triadic conversation style throughout every stage of the medical encounter, child participation may increase. What is Known: • Verbal child participation varies between 4 and 17%, measured in turns, words, speech time, or utterances. • Child participation is limited to social talk, laughter, and providing medical information. What is New: • Child speech turns equal parental speech turns (28%), but average relative word count remains low (11%). • Three percent of the children’s turns are defined a “contributing in decision making, giving their opinion or give consent,” which equals three turns per consultation.

The 1st step in the diagnostic process involves measurement of urinary oxalate, glycolate, and /or l-glycerate, followed by enzymatic analysis of AGT (in liver) or GR/ HPR (in lymphocytes), or genetic testing of the AGXT gene for PHl or the GRHPR gene for PH2. Therefore, episodes of urolithiasis, nephrocalcinosis, recurrent urinary tract infections, or unexplained decline of renal function require assessment of urinary oxalate to exclude PH.

PurposeThe added value of measuring patient-reported outcomes (PROs) for delivering patient-centered care and assessment of healthcare quality is increasingly evident. However, healthcare system wide data collection initiatives are hampered by the proliferation of patient-reported outcome measures (PROMs) and conflicting data collection standards. As part of a national initiative of the Dutch Ministry of Health, Welfare and Sport we developed a consensus-based standard set of generic PROs and PROMs to be implemented across Dutch medical specialist care.MethodsA working group of mandated representatives of umbrella organizations involved in Dutch medical specialist care, together with PROM experts and patient organizations worked through a structured, consensus-driven co-creation process. This included literature reviews, online expert and working group meetings, and feedback from national patient- and umbrella organizations. The ‘PROM-cycle’ methodology was used to select feasible, valid, and reliable PROMs to obtain domain scores for each of the PROs included in the set.ResultsEight PROs across different domains of health were ultimately endorsed: symptoms (pain & fatigue), functioning (physical, social/participation, mental [anxiety & depression]), and overarching (quality of life & perceived overall health). A limited number of generic PROMs was endorsed. PROMIS short forms were selected as the preferred instruments for all PROs. Several recommendations were formulated to facilitate healthcare system level adoption and implementation of the standard set.ConclusionsWe developed a consensus-based standard set of Generic PROMs and a set of recommendations to facilitate healthcare system wide implementation across Dutch medical specialist care.

Hyper-IgD and periodic fever syndrome (HIDS) and mevalonic aciduria (MA) are two autosomal recessive disorders that both are caused by a deficient activity of the enzyme mevalonate kinase (MK) due to mutations in the encoding gene ( MVK ). The most frequently occurring MVK mutation, V377I (1129G>A), has been identified exclusively in HIDS patients. Other common mutations have been associated with both HIDS and MA. To estimate the incidence of MK deficiency in the Netherlands, we determined the carrier frequency of the V377I mutation in genomic DNA extracted from anonymised newborn screening cards by PCR-RFLP. We found 14 carriers among 2138 analysed samples (1 : 153). Based on the V377I allele frequency of 42% in patients diagnosed with MK deficiency, the carrier frequency of any MVK mutation in the Dutch population can be calculated as 1 : 65. This predicts a disease incidence between1 in 5196 and 1 in 53 656, which is far more than actually observed. Although under-diagnosis ofpatients with MK deficiency remains possible, this discrepancy probably is due to a reduced penetrance of V377I homozygosity. Analysis of the distribution of the V377I allele within patients carrying MVK mutations revealed that this was not according to the Hardy–Weinberg equilibrium principle, most probably due to an under-representation of V377I homozygotes in HIDS. Homozygotes for V377I might exhibit a much milder phenotype of MK deficiency or no disease-phenotype at all.

ObjectiveThe objective of this study is to assess the impact of a multimodal intervention on emergency department (ED) crowding and patient flow in a Dutch level 1 trauma center.MethodsIn this cross-sectional study, we compare ED crowding and patient flow between a 9-month pre-intervention period and a 9-month intervention period, during peak hours and overall (24/7). The multimodal intervention included (1) adding an emergency nurse practitioner (ENP) and (2) five medical specialists during peak hours to the 24/7 available emergency physicians (EPs), (3) a Lean programme to improve radiology turnaround times, and (4) extending the admission offices’ openings hours.Crowding is measured with the modified National ED OverCrowding Score (mNEDOCS). Furthermore, radiology turnaround times, patients’ length of stay (LOS), proportion of patients leaving without being seen (LWBS) by a medical provider, and unscheduled representations are assessed.ResultsThe number of ED visits were grossly similar in the two periods during peak hours (15,558 ED visits in the pre-intervention period and 15,550 in the intervention period) and overall (31,891 ED visits in the pre-intervention period vs. 32,121 in the intervention period). During peak hours, ED crowding fell from 18.6% (pre-intervention period) to 3.5% (intervention period), radiology turnaround times decreased from an average of 91 min (interquartile range 45–256 min) to 50 min (IQR 30–106 min., p < 0.001) and LOS reduced with 13 min per patient from 167 to 154 min (p < 0.001). For surgery, neurology and cardiology patients, LOS reduced significantly (with 17 min, 25 min, and 8 min. respectively), while not changing for internal medicine patients. Overall, crowding, radiology turnaround times and LOS also decreased. Less patients LWBS in the intervention period (270 patients vs. 348 patients, p < 0.001) and less patients represented unscheduled within 1 week after the initial ED visit: 864 (2.7%) in the pre-intervention period vs. 645 (2.0%) patients in the intervention period, p < 0.001.ConclusionsIn this hospital, a multimodal intervention successfully reduces crowding, radiology turnaround times, patients’ LOS, number of patients LWBS and the number of unscheduled return visits, suggesting improved ED processes. Further research is required on total costs of care and long-term effects.