Parental perspectives on retention and secondary use of neonatal dried bloodspots: a Dutch mixed methods study.

BACKGROUND: Neonatal bloodspot screening (NBS) identifies conditions to offer early intervention and minimize irreversible damage. NBS policies guide a comprehensive system including processes for storage of neonatal dried blood spots (NDBS). NDBS retention and secondary use policies have been subject of public debates internationally, suggesting that the public's perceptions of NDBS policy are not always on par with existing policies. The current study aims to provide insight in relevant factors for new parents in the Netherlands regarding retention and secondary use of NDBS. These factors can be taken into account when developing or updating NDBS policies. METHODS: A mixed methods design was used combining an online survey (n = 753), focus groups (6 groups, 37 participants), and individual in-depth interviews (n = 7). The discussed topics included: parental information, obtaining informed consent, support for retention, and support for secondary use. The study population consisted of Dutch-speaking new parents: pregnant women (≥20 weeks) and/or their partner, and parents of at least one child (≤5 years). RESULTS: New parents expressed needs for easily accessible information, adequate communication on the retention and (potential) use of NDBS, clearly described safeguards for privacy, a more active consent process, regulation for the actors conducting NDBS research, and parental involvement in decisions on secondary use. Overall, participants were positive about prolonged retention and different types of secondary use if those needs were met. CONCLUSIONS: While parental involvement is a challenge, our study is an example of gauging parent's perspectives on NDBS policy and contributes to including these perspectives in the current policy discussion on longer retention. Prolonged retention could be a feasible option in the Netherlands if several prerequisites are met. Therefore, implementation studies involving parents are needed.

Radiative Rotational Lifetimes and State-Resolved Relative Detachment Cross Sections from Photodetachment Thermometry of Molecular Anions in a Cryogenic Storage Ring.

Photodetachment thermometry on a beam of OH^{-} in a cryogenic storage ring cooled to below 10 K is carried out using two-dimensional frequency- and time-dependent photodetachment spectroscopy over 20 min of ion storage. In equilibrium with the low-level blackbody field, we find an effective radiative temperature near 15 K with about 90% of all ions in the rotational ground state. We measure the J=1 natural lifetime (about 193 s) and determine the OH^{-} rotational transition dipole moment with 1.5% uncertainty. We also measure rotationally dependent relative near-threshold photodetachment cross sections for photodetachment thermometry.

HLA Class II Antibody Activation of Endothelial Cells Promotes Th17 and Disrupts Regulatory T Lymphocyte Expansion.

Kidney transplantation is the most successful treatment option for patients with end-stage renal disease, and chronic antibody-mediated rejection is the principal cause of allograft loss. Predictive factors for chronic rejection include high levels of HLA alloantibodies (particularly HLA class II) and activation of graft endothelial cells (ECs). The mechanistic basis for this association is unresolved. We used an experimental model of HLA-DR antibody stimulation of microvascular ECs to examine the mechanisms underlying the association between HLA class II antibodies, EC activation and allograft damage. Activation of ECs with the F(Ab')2 fragment of HLA-DR antibody led to phosphorylation of Akt, ERK and MEK and increased IL-6 production by ECs cocultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an Akt-dependent manner. We previously showed that HLA-DR-expressing ECs induce polarization of Th17 and FoxP3(bright) regulatory T cell (Treg) subsets. Preactivation of ECs with anti-HLA-DR antibody redirected EC allogenicity toward a proinflammatory response by decreasing amplification of functional Treg and by further increasing IL-6-dependent Th17 expansion. Alloimmunized patient serum containing relevant HLA-DR alloantibodies selectively bound and increased EC secretion of IL-6 in cocultures with PBMCs. These data contribute to understanding of potential mechanisms of antibody-mediated endothelial damage independent of complement activation and FcR-expressing effector cells.

Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases.

Inflammatory bowel diseases are characterized by a deregulated immune response targeting the gut bacterial flora. Mucosal-associated invariant T (MAIT) cells are major histocompatibility complex (MHC) class Ib-restricted innate-like lymphocytes with anti-bacterial functions. They display an effector/memory phenotype and are found in large numbers in the blood, mucosae and liver. They have also been implicated in inflammatory diseases such as multiple sclerosis. Therefore, we aimed to analyse the possible involvement of MAIT cells in Crohn's disease (CD) and ulcerative colitis (UC). To this end, a phenotypical and functional analysis of MAIT cells isolated from the blood of healthy subjects, CD and UC patients was undertaken. MAIT cells were also quantified in ileal biopsies of CD patients. The frequency of blood MAIT cells was specifically reduced in IBD patients compared with healthy donors, whereas it was dramatically greater in the inflamed versus healthy tissue. MAIT cells were activated as they expressed significantly more the Ki67 antigen, and this was accompanied by phenotypical changes such as increased expression of natural killer (NK)G2D and B and T lymphocyte attenuator (BTLA). Finally, in-vitro-activated MAIT cells from CD and UC patients secreted significantly more interleukin (IL)-17, together with a decreased interferon (IFN)-γ in CD but an increased IL-22 in UC. These data show that MAIT cells are activated in IBD, which results in an increased recruitment towards the inflamed tissues, an altered phenotype and a switch in the pattern of cytokine secretion. This is the first demonstration that MAIT cells are immune players in IBD, whose precise functions in this context need to be addressed.

Parents' views on accepting, declining, and expanding newborn bloodspot screening.

INTRODUCTION: The goal of newborn bloodspot screening (NBS) is the early detection of treatable disorders in newborns to offer early intervention. Worldwide, the number of conditions screened for is expanding, which might affect public acceptance. In the Netherlands, participation is high (>99%), but little is known about how parents perceive NBS. This study assessed parents' views on accepting, declining and expanding NBS. METHODS: A total of 804 of 6051 (13%) invited parents who participated in NBS in the Netherlands during the last two weeks of December 2019, and 48 of 1162 (4%) invited parents who declined participation in NBS in 2019 and 2020, completed a questionnaire. RESULTS: The most important reason for parents to participate in NBS was to prevent health complaints, whereas the most important reason to decline NBS was parents' viewpoint on life and the belief that the heel prick would be painful for the child. Compared to NBS participants, respondents who declined NBS were more actively religious, considered alternative medicine or lifestyle more important, were less inclined to vaccinate their child for infectious diseases, and reported more doubt about NBS participation (all differences p < .001). Informed choice was lower among respondents who declined NBS (44%) compared to participants in NBS (83%, p < .001), mostly due to insufficient knowledge. Of the NBS participants, 95% were positive about NBS expansion. Most NBS participants agreed to include conditions that could unintentionally reveal a diagnosis in the mother instead of the child (86%) or a condition that may not cause symptoms until later in the child's life (84%). CONCLUSION: Most participants made an informed decision to participate in NBS and are positive about screening for more conditions. Insights into parents' views on (non-)participation and expansion of NBS can help to ensure that NBS suits the population needs while safeguarding ethical principles for screening.

Production of glucuronan oligosaccharides using a new glucuronan lyase activity from a Trichoderma sp. strain.

Sinorhizobium meliloti M5N1CS synthesizes a homopolymer of glucuronic acids beta-(1,4) linked and variably C2 and/or C3O-acetylated. To obtain beta-Delta-(4,5)-unsaturated oligoglucuronans, various acetylated forms of this bacterial polymer were cleaved by a Trichoderma sp. GL2 glucuronan lyase. Oligomers with polymerization degrees up to 8 were then produced, purified by liquid chromatography (size exclusion and anions exchange) and characterized using 1H NMR and ESI-Q/TOF-MS. Finally, the production (in gram quantity) of pure unsaturated oligoglucuronans non-acetylated (di- and trisaccharide) was investigated thanks to the complete depolymerization of deacetylated glucuronan.

Problems in the diagnosis of intermittent explosive disorder.

The authors studied the accuracy with which intermittent explosive disorder was diagnosed in a university hospital setting. An index of diagnostic features abstracted from the description of intermittent explosive disorder in DSM-III was used for chart review. Diagnosis of the disorder was made in 20 out of 830 admissions (2.4%). In 14 cases (1.7%) it was a primary one; in another five (.6%) it was secondary; and in one case (.1%) it was tertiary. The authors discuss the varied rigorousness of the diagnosis and the importance of using an index of diagnostic features to enhance diagnostic accuracy.

Assaults on psychiatrists by patients.

The authors describe the results of a survey of 115 psychiatrists regarding assaults by patients. Forty-eight psychiatrists stated that they had been assaulted; a total of 68 assaults was reported. Psychiatrists were most often assaulted in the early stages of their career or while they were working in high-risk settings such as prisons or emergency rooms. Many reported retrospectively that they might have had a role in provoking the assault and that they could have anticipated it. The authors believe that psychiatrists avoid dealing with the issue of violence by patients for a variety of reasons, and they recommend that clinicians learn techniques for managing potentially assaultive patients.

A violence clinic: three years' experience.

The authors describe a clinical facility established for the neuropsychiatric treatment of individuals with a variety of psychopathological disorders where the common management problem is one of aggressive behavior. The authors present case vignettes to illustrate the clinic's consultation with mental health workers about the management of violent patients, countertransference problems, ward problems, the role of organic factors, medication, and prediction of violence. They urge that the subject of violence be included in the psychiatrist's training.

Psychiatric care for patients with self-inflicted gunshot wounds.

Self-inflicted gunshot wounds are the commonest form of suicide in this country. Seventeen individuals with such injuries were admitted to a trauma center over a 3-month period. Review of their records showed that psychiatric consultation was requested for only nine of the 13 patients who survived their wounds. Information on alcohol use was missing from half the case records and only six of the 13 survivors received psychiatric care after discharge. Use of guns in suicide attempts may evoke strong feelings in health care providers, resulting in omissions in history taking, evaluation, and follow-up.

Benzodiazepines in the treatment of aggressive patients.

A double-blind, controlled clinical trial of chlordiazepoxide, oxazepam and placebo was conducted in 65 outpatients with past histories of temper outbursts, assaultive behaviour and impulsiveness associated with anxiety, irritability and hostility. Of those tests showing statistically significant results, there was a tendency for oxazepam to be somewhat more effective in the reduction of anxiety than chlordiazepoxide. Oxazepam was also superior to the latter on 1 subscale of tests used to measure hostility. No paradoxical rage responses were noted.

Hyperaldosteronism (Conn's disease) presenting as depression.

A case of muscle weakness with hypertension is presented. The patient had symptoms of depression. Diagnosis of hyperaldosteronism was suspected because of a low serum potassium and confirmed by discovery of an adrenal adenoma. The role of hypokalemia in mental disturbances is reviewed. Emphasis is placed on possible metabolic etiologies when mood changes, muscle paresis and hypertension coexist.

Down-regulation of ACTH and glucocorticoid receptor immunoreactivity in hypothalamic arcuate neurons after adrenalectomy in the rat.

The expression of glucocorticoid receptor (GR) in rat adrenocorticotropin (ACTH)-containing neurons in rat brain was immunohistochemically investigated. ACTH-containing cell bodies were found mainly in the arcuate nucleus. Most of these neurons exhibited GR immunoreactivities in their nuclei. ACTH-containing nerve fibers were distributed in the bed nucleus of the stria terminalis, periventricular nucleus, retrochiasmatic nucleus, parvocellular part of paraventricular nucleus and dorsomedial hypothalamic nucleus. After adrenalectomy there was a marked decrease of ACTH immunoreactivity, as well as GR immunoreactivity, in neurons of the arcuate nucleus, but ACTH immunoreactivity in the fibers was not affected. These results indicate that glucocorticoids up-regulate ACTH and GR production in hypothalamic arcuate neurons, but that glucocorticoid-induced changes could be delayed in the fibers derived from these neurons.

The clinician's role in assessing workplace violence.

Workplace violence can be an area of consultation for psychiatrists. However, the clinician must understand not only the limits of violence prediction, but also the corporate culture in which he or she will become involved. Evaluation of threats may involve review of written notes or taped recordings; the employee may or may not be seen. Corporate consultations sometime involve a split allegiance on the part of the clinician who must both advise the company and render a decision about the employee. The dynamics of violence within the workplace are discussed.

Pharmacologic approaches to violence.

No one drug is specific for the management of violent behavior. Rather, the pharmacologic treatment of aggression is best approached by identifying and treating the underlying psychopathology, with the expectation that the violent behavior will resolve secondarily. Pharmacologic management is probably most successful when other treatment modalities such as family, group, and individual psychotherapies are used concurrently.

Case-mix differences between hospital outpatient departments and private practice.

The belief that patients seen in hospital outpatient departments are sicker than those patients seen by private practice physicians is examined in this article. A large scale data set developed by Robert Mendenhall at the University of Southern California and modeled on the National Ambulatory Medical Care Survey (NAMCS) is used for secondary analysis. Differences in case-mix complexity were found to be slight, using two separate techniques.

Case mix and charges for inpatient and outpatient chemotherapy.

Case mix and charges for chemotherapy treatment were examined by an analysis of the inpatient discharges for DRG 410 (chemotherapy) from eight teaching hospitals and of outpatient visits from two teaching hospitals. Discharges for ovarian cancer were the most common and the least expensive, costing $1,600 or half as much as the most costly, less common conditions (leukemia and testicle cancer). Diagnosis explained 13 percent of the inpatient charge variation; metastasis explained less than 1 percent. Outpatient chemotherapy overlapped with inpatient among only 3 of the 10 most common diagnoses. The implication is that the two settings are complementary with regard to chemotherapy administration.

A comparison of hospital outpatient departments and private practice.

This article addresses cost differences between primary care physicians in private practice and hospital outpatient departments (OPD's). The analysis utilizes ambulatory visit groups (AVG's), the outpatient equivalent of diagnosis-related groups (DRG's), to adjust for case mix. Major findings are that OPD's have higher per visit costs than physicians' private offices; internists are more expensive than general practitioners regardless of site; and ancillary service costs are actually slightly higher in private practice. Any prospective payment system for ambulatory care must consider these costs differences.

Toward a prospective payment system for ambulatory surgery.

In this article, ambulatory surgery among the aged Medicare population in 1985 is examined. Total hospital facility charges for ambulatory surgery in that year were estimated at $1.8 billion, with about one-half of that amount involving cataract surgery. The possibility of using diagnosis-related groups for a prospective payment system for ambulatory surgery was examined and was rejected for two reasons: (1) about 20 percent of the dollar volume of hospital-based ambulatory surgery fell into medical diagnosis-related groups and (2) the ratio of inpatient diagnosis-related group weight to outpatient billed charges for the ambulatory procedures falling into a given diagnosis-related group varied more than tenfold, making diagnosis-related group weights impossible to use in a consistent manner. A newly developed version of ambulatory visit groups and the even newer ambulatory patient groups were then considered as an alternative for a prospective payment system. These are briefly described.