Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study.

Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment-including echocardiography and blood sampling-before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3-10.3] months, and 28 TCPC patients aged 2.7 [2.2-3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (-15.1 ± 5.6 (T1) to -13.5 ± 5.2 (T2) to -17.3 ± 4.5 (T3), p < 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell-cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome.

Progesterone for prevention of preterm birth in women with short cervical length: 2-year infant outcomes.

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Consent for treatment: a results or a reasonable endeavours agreement? Two alternatives with significant practical differences to dentists]. / De behandelingsovereenkomst: een resultaats- of een inspannings­verbintenis? Twee alternatieven met grote praktische verschillen voor de tandarts.

The character of a consent for treatment is not a mere hobby for lawyers; it also has consequences in daily practicein the Netherlands, particularly if it concerns questions of who should prove what in proceedings. In general, consent agreements can be divided into an obligation to achieve results and an obligation to use reasonable endeavours. In oral healthcare, there is usually a question of an obligation to use reasonable endeavours, in which professional standards must play a leading role in the behaviour of the dentist; and here there have been a number of recent developments, such as an increase in the number of (clinical) guidelines and the acceptance of wish fulfilling medicine, under strict conditions. It is concluded that recent developments in the dentist's requirement to provide evidence in proceedings have definitely not made things simpler.

Multicentre reference values for cardiac magnetic resonance imaging derived ventricular size and function for children aged 0-18 years.

AIMS: Cardiovascular magnetic resonance (CMR) imaging is an important tool in the assessment of paediatric cardiac disease. Reported reference values of ventricular volumes and masses in the paediatric population are based on small cohorts and several methodologic differences between studies exist. We sought to create steady-state free precession (SSFP) CMR reference values for biventricular volumes and mass by combining data of previously published studies and re-analysing these data in a standardized manner. METHODS AND RESULTS: A total of 141 healthy children (68 boys) from three European centres underwent cine-SSFP CMR imaging. Cardiac structures were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation according to current standardized CMR post-processing guidelines. Volumes and masses were derived from these contours. Age-related reference curves were constructed using the lambda mu sigma method. Median age was 12.7 years (range 0.6-18.5). We report biventricular volumes and masses, unindexed and indexed for body surface area, stratified by age groups. In general, boys had approximately 15% higher biventricular volumes and masses compared with girls. Only in children aged <6 years old no gender differences could be observed. Left ventricle ejection fraction was slightly higher in boys in this study population (median 67% vs. 65%, P = 0.016). Age-related reference curves showed non-linear relations between age and cardiac parameters. CONCLUSION: We report volumetric SSFP CMR imaging reference values for children aged 0-18 years old in a relatively large multi-centre cohort. These references can be used in the follow-up of paediatric cardiac disease and for research purposes.

[The new law concerning complaints in practice]. / Het nieuwe klachtrecht in de praktijk.

Most patients who file a formal complaint against a dentist do so by way of the law concerning complaints. In 2017 the law concerning complaints was changed radically, with the intention of making the law easier for the patient to make use of and providing the patient with a financial settlement. This article considers the extent to which the possibility of being compensated has had the effect of encouraging patients to file claims in the case of the Royal Dutch Dental Association (KNMT), the complaints service with which most dentists are associated. The article also considers whether the new law has made the process of filing a complaint more readily accessible. Finally, if the law of complaints has become more appealing for patients to make use of, one could imagine that fewer cases would find their way to the disciplinary board. For that reason, the number of disciplinary complaints in 2017 is compared to the number for 2016.

[Evidence-based clinical guidelines in dental practice 5. Guidelines: professional autonomy and right of self-determination]. / Evidencebased klinische praktijkrichtlijnen in de mondzorg 5. Richtlijnen: professionele autonomie en zelfbeschikkingsrecht.

Judges up to and including the Law Lords (Supreme Court) and the Central Disciplinary Tribunal for Healthcare in the Netherlands do not consider guidelines to be optional. This offers security to patients and dental care professionals. But a field of tension can exist between, on the one hand, a patient's right of self-determination and the dental care workers professional autonomy and, on the other, a guideline. This field of tension can be resolved by first limited testing of the acceptability of the goal of care desired by the patient, taking into consideration at the same time professional autonomy; and, subsequently, by selecting the most effective treatment for achieving this goal of care on the basis of 'evidence'. With respect to the current definition of guidelines for clinical practice, this means that patients and healthcare workers explicitly acknowledge that they have been able to agree on a goal of care that deviates from the ideal. In this way, a judicially responsible balance is achieved between the right of self-determination and professional autonomy, on the one hand, and, on the other, the desire for evidence-based treatment and a limitation on unaccountable variation in treatment and transparency of care.

[Dentistry and healthcare legislation 11. The dentist and the civil law judge: claims]. / Tandheelkunde en gezondheidsrecht 11. De tandarts en de civiele rechter: claims.

In contrast to the law governing complaints and to disciplinary law, a civil law judge can sentence dentists to the restoration of all damages to patients. For this to happen, there has to be evidence of damage, responsibility and a causal connection. For the assumption of responsibility as well as a causal connection, an important question is whether a dentist has violated a relevant guideline or protocol. Moreover, dentists are not only responsible for their own mistakes, but also, in principle, for those of their employees. Depending on the situation, dentists can also be held accountable for the mistakes of a dentist who is working in their practice on a self-employed basis. Dutch dentists do not yet have to fear American situations', because damages awarded in The Netherlands are still relatively low.

[Dentistry and healthcare legislation 10. The law governing complaints: readily accessible filing procedures]. / Tandheelkunde en gezondheidsrecht. 10. De Wet klachtrecht: laagdrempelig klagen.

The law promises patients a readily accessible means of filing complaints. Healthcare providers are therefore required to adopt regulations governing complaints which satisfy a number of conditions. Most dentists choose to adopt the regulations which have been established by their professional organization. In addition to handling complaints, there is also a provision for mediation, which is often used by patients. Mediation appears, then, to be a successful provision. Many complaints have their origin in insufficient knowledge of healthcare legislation and patients' rights legislation. This demonstrates that more attention should be given to these subjects in educational programmes and programmes in continuing education. The present law governing complaints is expected to be replaced this year by a new, more comprehensive law in which considerable attention will be devoted to the quality of care as well as to complaints. It seems likely, however, that the new law governing complaints will damage the effective manner in which patients' complaints are dealt with in dentistry today.

[Dentistry and healthcare legislation 9. The dentist and the disciplinary court case]. / Tandheelkunde en gezondheidsrecht 9. De tandarts en de tuchtrechtprocedure.

Disciplinary law can be seen as an element in the system that protects the quality of dental care and in that way helps to maintain the high level of trust which the public has in the profession. A disciplinary court case is regarded by dentists as very taxing. This is in part a result of unfamiliarity with the procedure. The procedure is also feared because of the publicity it attracts. The publicity is partly inherent in the goal of the disciplinary law. To some extent the publicity seems to be taking on the character of 'trial by media'. Questions can be raised with respect to this latter development, regarding, for example, the use of anonymity by journalists; the impact of publication, which is partially dependent on other news-worthy events; and the impact of the publication of reprimands versus the most severe sanction.

[Dentistry and healthcare legislation 8. Registration and termination of registration of patients: the disciplinary judge determines the norm]. / Tandheelkunde en gezondheidsrecht 8. In- en uitschrijven van patiënten: de tuchtrechter stelt de norm.

The extent of the responsibility to provide care which a dentist bears depends on whether a patient is registered with the dentist's practice. A dentist has the freedom not to register a patient with his practice, provided he does not violate the anti-discrimination laws or a cooperative professional agreement which the dentist has signed. No conditions are applied if a patient wishes to withdraw his registration, or a registration is withdrawn by mutual agreement. If a dentist wishes to terminate the treatment agreement unilaterally, this can only be done if serious reasons for doing so can be identified. The reasons for termination which will be accepted by disciplinary boards as serious depend very much on the conditions of the specific case. In cases of the unilateral termination of a treatment agreement on the part of a dentist, given the serious reasons for doing so, it is usually necessary for a dentist to take into consideration various requirements for careful conduct.

Extended-spectrum ß-lactamase producing Klebsiella spp. in chicken meat and humans: a comparison of typing methods.

Recently, chicken meat was identified as a plausible source of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli in humans. We investigated the relatedness of ESBL-producing Klebsiella spp. in chicken meat and humans. Furthermore, we tested the performance of SpectraCell RA(®) (River Diagnostics), a new typing method based on Raman spectroscopy, in comparison with multilocus sequence typing (MLST) for Klebsiella pneumoniae. Twenty-seven phenotypically and genotypically confirmed ESBL-producing Klebsiella spp. isolates were typed with MLST and SpectraCell RA. The isolates derived from chicken meat, human rectal swabs and clinical blood cultures. In the 22 ESBL-producing K. pneumoniae isolates, CTX-M15 was the predominant genotype, found in five isolates of human origin and in one chicken meat isolate. With MLST, 16 different STs were found, including five new STs. Comparing the results of SpectraCell RA with MLST, we found a sensitivity of 70.0% and a specificity of 81.8% for the new SpectraCell RA typing method. Therefore, we conclude that SpectraCell RA is not a suitable typing method when evaluating relationships of ESBL-producing Klebsiella spp. at the population level. Although no clustering was found with isolates of chicken meat and human origin containing the same ESBL genes, MLST showed no clustering into distinctive clones of isolates from chicken meat and human origin. More studies are needed to elucidate the role of chicken meat in the rise of ESBL-producing Klebsiella spp. in humans.

[Dentistry and healthcare legislation 5. Confidentiality and privacy]. / Tandheelkunde en gezondheidsrecht 5. Geheimhouding en ruimtelijke privacy.

The right to confidentiality and privacy is established in various laws and in many cases the violation of these laws provokes a reaction in the form of severe sanctions. Nevertheless, patients complain relatively seldom about violations ofprivacy laws by dentists. The right to privacy consists of a requirement of confidentiality on the part of those carrying out treatment and the patients' right to be treated without being observed by third parties. 'Third parties' do not include those involved in the treatment or someone who represents the patient. The right to confidentiality can be violated if a patient grants consent, in cases of a legal requirement or in cases ofa conflict of requirements. A separate regulation exists concerning the confidentiality and privacy of patients in the context of scientific research.

[Dental and health law 4. The treatment of minors and of adults who are unable to give informed consent]. / Tandheelkunde en gezondheidsrecht 4. De behandeling van minderjarigen en meerderjarige wilsonbekwamen.

When minors are treated, a complex triangular relationship can emerge among dentist, patient and the individual legally responsible for the patient. Generally speaking, both parents are those legally responsible for a child. This might not be the case if the parents are not married to each other or have divorced, or when there is a question of a child protection ruling. The governing rule is that dentists are required to honour the obligations to the legal representatives thatfollow from the patients' rights concerning the treatment of children under the age of 12. In the case of patients between the ages of 12 and 16, dentists are required to act in accordance with their obligations to both those legally responsible and to the patients. Finally, in the case ofpatients who are 16 and older, dentists are required to act only in accordance with their obligations to the patients. There are, however, various exceptions to this governing rule. One of the most common examples is the patient who is a minor of 16 or older who is unable to determine what is in his own best interest. That criterium is also used in determining the capability to give informed consent in adults.

[Requirements regarding health records: transfer or copy]. / Dossierplicht: overdracht of afschrift.

Dutch law requires every healthcare provider, which obviously includes dentists, to maintain health records. Most of the rules governing the health record requirement are in the Law of Agreement to Medical Treatment (WGBO). And, as is often the case with the law, interpretation is left to the (disciplinary)judge. There is, in fact, a considerable amount of legal precedent concerning what information belongs in the health record. It is not uncommon for a dentist to be on the losing side in a legal proceeding because his defence is not supported by the health record. And if it becomes clear that (a portion of) the health record has been destroyed, despite the legal requirement to maintain records, in this too the dentist can count on little sympathy from the judge. In a recent judgment, the Central Disciplinary Committee was more severe than ever- with far-reaching consequences for the relevant dentist.

[Dentistry and healthcare legislation 3: informed consent]. / Tandheelkunde en gezondheidsrecht 3. Informed consent.

The relationship between a dentist and his patient is based on trust. The principle of informed consent contributes to the quality of that relationship of trust. According to the professional standards for such a relationship, it is up to the dentist to make sure that the patient is well informed. Reliable information is necessary if the patient is to be in a position to give his or her consent for treatment. The Dutch Law of Agreement to Medical Treatment (WGBO) provides aframework for informed consent. Disciplinary judges establish the scope and if necessary the limits. It is clear that, among other things, not defining the risks beforehand can be the basis for a (disciplinary) complaint. Determining the requirements of informed consent calls for familiarity with the law and communication skills. Programmes in dental education ought to devote more attention to this issue.

[Dentistry and healthcare legislation 2. Differences of opinion concerning professional standards for oral healthcare]. / Tandheelkunde en gezondheidsrecht. 2. Meningsverschillen over de zorginhoudelijke professionele standaard.

With respect to disciplinary and other complaints, it is apparent that they are often based on a difference of opinion concerning professional standards for oral healthcare. Relevant differences of opinion can arise between dentists, but also in the dentist-patient relationship. A large degree of the ambiguity which lies at the basis of such discussions could be removed by the use of clear clinical guidelines. Since these are still scarce in oral healthcare, a dentist will have to rely on adequate communication to avoid conflicts. A dentist must be aware of possible conflicts of interest and of the characteristic range of the professional standards for oral healthcare. Departing from that range at the request of a patient is not an option.

[Dentistry and health care legislation 1. Professional standard for oral healthcare delivery]. / Tandheelkunde en gezondheidsrecht 1. De zorginhoudelijke professionele standaard.

A dentist should deliver oral healthcare according to the professional standard. This legal determination is not very distinct and ought to be made more specific. Guidelines, protocols, and indicators play an important role in this respect, but are scarce in oral healthcare. Provisionally, judgements of discipline and complaints committees are heavily relied upon. Those judgements indicate what efforts, and in some cases even what results, a patient could have expected from a dentist in the specified conditions.

[Dentistry and healthcare legislation 7. The duty to provide care: availability and accessibility]. / Tandheelkunde en gezondheidsrecht 7. De hulpverleningsplicht: beschikbaarheid en bereikbaarheid.

Dentists have a duty to provide care. This duty, which interestingly enough has a limited legal basis, is for the most part given form by jurisprudence. In that process, the disciplinary judge and the grievance committees pay attention especially to 2 rules of conduct and 1 regulation governing practice. In practice, it appears to be the case that rules of conduct and regulations do not always provide an unambiguous guide. The domain within which dentists operate is striking. The availability and the accessibility of dentists are not always harmonious with the personal perception of a patient. It is sometimes difficult to find a proper balance between what is a dentist is able to manage and what a patient wants.

[Dentistry and healthcare legislation 6. The effect of self-regulation in dental healthcare]. / Tandheelkunde en gezonheidsrecht 6. Het effect van zelfregulatie in de mondzorg.

Regulations which have been established by the professional community or by an organization of which a dentist is a member (self-regulation) have a more significant legal effect on dental care than many dentists realize. A dentist can only deviate from these regulations if he does so when motivated by the patient's best interests. Self-regulation can be relevant at the level of the professional community, the organization or the individual dentist. Self-regulation should satisfy a number of criteria if it is to be applicable to an entire professional community, specifically: it must be sufficiently authoritative, it must harmonize with existing laws and regulations and it must be easily accessible to both professionals and patients. The application of self-regulation is sometimes limited to a specific group, for example dentists who have signed a working agreement with a certain health insurance provider or who work in a certain institution. Self-regulation can entail liability not only on the part of the healthcare professional but also, in theory, on the part of those who establish the regulations.

[Disciplinary board censures improper delegation]. / Tuchtcollege hekelt onterechte delegatie.

A regional disciplinary board censured a dentist who allowed someone without proper authorisation to carry out a procedure and that judgement was the motivation for providing some clarification concerning the Dutch law. In the Netherlands, more than in most other countries, a relatively large amount of freedom is given to people who are not medical doctors to carry out dental procedures. This freedom does, however, have its limits and they are established in the law governing the registration of healthcare professionals (in the BIG-register). The central requirement in this law is competence. In addition, the law makes a distinction, at the present time, among a group of healthcare providers who are authorised to carry out, independently, restricted treatments (dentists), a group of healthcare providers who are authorised to perform certain functions (dental hygienists), and a group who are not authorised. Provided they satisfy legal requirements, non-authorised individuals can also carry out restricted treatments. In the future, this system might be breached, in the sense that the requirementfor authorisation will lapse.