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.

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.

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.

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.

Threats against clinicians: a preliminary descriptive classification.

Threats against psychiatrists are common, but existing studies on the subject lack descriptive information about the nature and resolution of the threat. In the present study, clinicians who had received threats were interviewed in person or by telephone, and case histories were summarized. Threats were classified as situational and transferential. Demographic factors, precipitating events, and legal actions taken are described. The manner in which clinicians reacted to threats is also discussed.

Effect of patient characteristics and disease manifestations on the outcome of acute otitis media at 2 months.

BACKGROUND: Optimal therapy for acute otitis media (AOM) is controversial and there is no consensus regarding which antibiotic to use, how long to administer it, or whether antibiotics are effective at all. Knowledge of the effects of patient characteristics and disease manifestations is needed to individualize treatment and to evaluate large-scale trials. METHODS: Data originated from 2251 patients with AOM, aged newborn to 15 years, who participated in a prospective primary care study in eight countries. At the initial visit, medical history, symptoms, physical findings, and treatment data were recorded. Follow-up 2 months later identified changes in treatment and outcome. RESULTS: Patients younger than 13 months were less likely to have recovered than those aged 13 months to 15 years (P = .05). Using univariate analysis for infants aged 12 months or younger, male sex, prior episodes of AOM, and serous otitis media were associated with poor outcome. For older patients, poor outcome was associated with initial history of ear tubes, prophylactic antibiotic use, ear discharge, decreased hearing, serous otitis media; and past episodes of AOM; the symptom of decreased hearing; and the finding of pus exuding from the tympanic membrane. Using multivariate analysis for infants aged 12 months or younger, a history of serous otitis media (odds ratio [OR], 2.3; 95% confidence interval [CI], 0.95-5.7), past episodes of AOM (OR, 1.9; 95% CI, 0.82-4.5), and male sex (OR, 1.7; 95% CI, 1.0-3.0) made independent contributions to poor outcome. For children aged 13 months to 15 years, significant variables included pus drainage (OR, 2.2; 95% CI, 1.5-3.3), a history of ear tubes (OR, 2.3; 95% CI, 1.5-3.6), past episodes of AOM (OR, 1.8; 95% CI, 1.3-2.34), and a history of serous otitis media (OR, 1.4; 95% CI, 1.0-1.9). CONCLUSIONS: Patient characteristics and disease manifestations are significant determinants of AOM outcome.

Acute otitis media in adults: a report from the International Primary Care Network.

BACKGROUND: Of 22 million visits annually to United States physicians for acute otitis media, almost 4 million are by patients 15 years old or older. Yet the clinical spectrum and variables related to recovery have not been reported for adults. METHOD: Data originated from 3224 primary care patients with acute otitis media, of whom 500 were 15 years old or older, who were enrolled in a prospective study in eight countries. At the initial visit, history, symptoms, physical findings, and treatment were recorded. At a 2-month follow-up visit, changes in treatment and recovery were recorded. RESULTS: Compared with children, adults sought care more quickly after symptom onset; were more likely to have had a tonsillectomy or adenoidectomy; and were more likely to complain of ear pain, decreased hearing, sore throat, and ear discharge. Children were more likely to have a history of recent upper respiratory tract infection, serous otitis media, and ear tubes; symptoms of fever, diarrhea, and vomiting; and tympanic membrane findings of redness, bulging, and ear tubes in place. History of reduced hearing, allergy, prophylactic antibiotics, and tympanic membrane findings characterized as opaque or dull, fluid, draining pus, perforation, and not visualized were equally frequent in both age groups. For adults, neither type nor duration of antibiotic affected outcome. Patients receiving antibiotics had lower rates of recovery than those who did not. The likelihood of a poor outcome increased with an increasing number of past episodes of acute otitis media and with increasing age. CONCLUSION: Although history and symptoms differ in adults and children, the similarity of tympanic membrane findings is consistent with previous reports of a similar bacterial spectrum in both groups. Recovery is related more to individual patient characteristics and history than to antibiotic therapy. Adults have an increased rate of poor outcome at 2 months compared with children.

Five years of sentinel surveillance of acute respiratory infections (1985-1990): the benefits of an influenza early warning system.

For the last five years, the Brussels Institute of Hygiene and Epidemiology has been involved in the surveillance of acute respiratory infections (ARI). The four indicators used (number of encounters of ARI by GP's/100 encounters, virus isolations, absenteeism and mortality) are discussed. A regression procedure is applied to the data collected by a sentinel network of general practitioners (GP's). This procedure permits the baseline to be visualized and an epidemic threshold to be determined in order to recognize early an influenza outbreak. The traditional use of flu-like illnesses as an indicator might be improved by the addition of non-specific ARI which are more precocious, especially in children. The criteria for an accurate definition of an influenza epidemic are discussed. The same mathematical model can be used for the analysis of mortality linked with an outbreak. It shows that the last epidemic in the winter 1989-1990 was responsible for about 4900 deaths directly or indirectly related to influenza.

A sentinel network of microbiological laboratories as a tool for surveillance of infectious diseases in Belgium.

In the development of a surveillance programme for infectious diseases in Belgium, a national network of microbiological laboratories has been responsible, since February 1983, for the weekly registration of certain pathogenic agents. Thus, the main epidemiological features of a selected number of infections in Belgium can be characterized.

Psychiatric visits to general hospital clinics by elderly persons and younger adults.

Findings of a study of mental health visits to general hospital outpatient clinics and emergency rooms by elderly persons and younger adults were compared with findings from an earlier survey of mental health visits to office-based physicians. In both studies, about half of the visits were to psychiatric clinics or to psychiatrists. However, the findings differed in that 43 percent of all visits to hospital clinics were for substance abuse, compared with only 4 percent of the visits to private physicians. Almost three-fourths of the hospital-based mental health visits by elderly patients were to psychiatric clinics, while only a third of the office visits by elderly patients were to psychiatrists. The authors discuss the policy implications of the high utilization of clinic services by elderly patients.

Diagnosis and antibiotic treatment of acute otitis media: report from International Primary Care Network.

STUDY OBJECTIVE: The relation between a history of disorders suggestive of acute otitis media, symptoms, and findings of an examination of the tympanic membrane and doctors' certainty of diagnosis. Also, to examine differences in prescribing habits for acute otitis media among doctors from different countries. DESIGN: Questionnaires were completed by participating doctors for a maximum of 15 consecutive patients presenting with presumed acute otitis media. SETTING: General practices in Australia, Belgium, Great Britain, Israel, The Netherlands, New Zealand, Canada, Switzerland, and the United States. PATIENTS: 3660 Children divided into the three age groups 0-12 months, 13-30 months, and greater than or equal to 31 months. MAIN OUTCOME MEASURES: General practitioners' responses to questions on their diagnostic certainty and resolution of patients' symptoms after two months. RESULTS: The diagnostic certainty in patients aged 0-12 months was 58.0%. This increased to 66.0% in those aged 13-30 months and 73.3% in those aged greater than or equal to 31 months. In all age groups diagnostic certainty was positively associated with the finding of a tympanic membrane that was discharging pus or bulging. Redness of the membrane and pain were also associated with certainty in patients aged 13-30 months, and a history of decreased hearing or recent upper respiratory infection was positively associated in patients aged greater than or equal to 31 months. The proportion of patients prescribed antibiotics varied greatly among the countries, from 31.2% in The Netherlands to 98.2% in both Australia and New Zealand, as did the duration of treatment. Patients who did not take antibiotics had a higher rate of recovery than those who did; the rate of recovery did not differ between different types of antibiotic. CONCLUSIONS: Doctors' certainty of diagnosis of acute otitis media was linked to patient's age. Improved criteria or techniques for diagnosing acute otitis media, especially in very young children, need to be developed. Antibiotic treatment did not improve the rate of recovery of patients in this study.

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.