Coagulation studies on umbilical arterial and venous blood from normal newborn babies

Coagulation studies using conventional methods and chromogenic substrates were performed on umbilical arterial and venous blood from 33 newborns after delivery. In the arterial samples, thrombin time (TT) was significantly prolonged and the activities of factors I, II, V and VII, as well as the inhibitors heparin, antithrombin III and antiplasmin, were significantly decreased. This could probably be explained by a mild form of disseminated intravascular coagulation (DIC) occurring in the baby during delivery.With support of the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen     

Vitamin E concentrations in term and preterm newborns and their clinical course

Vitamin E deficiency in premature infants has been described as being associated with low hemoglobin levels in the 2nd month of life. Recently, low vitamine E concentrations were suspected as being associated with sudden death in infancy. As vitamin E is absorbed incompletely from the premature's intestine, vitamin E levels in the serum were determined in 80 prematures on the 10th day of life. The result was correlated to the clinical course of the infants and to the hemoglobin levels up to the 30th day.Low concentrations of vitamin E and lower hemoglobin levels were found more frequently in newborns, whose clinical course was characterized by additional complications and who received parenteral nutrition. A group of uncomplicated newborns showed no correlation of vitamin E to hemoglobin values. Thus early diagnosis of vitamin E-dependent anemia is not possible and the usefulness of vitamin E should be investigated only in newborns with an uneventful clinical course.Auszugsweise vorgetragen anläßlich der 24. Tagung der Nordwestdeutschen Gesellschaft für Kinderheilkunde, Kiel, 6.-8. 6. 1975.     

Facilitators and barriers to implementing task shifting: Expanding the scope of practice of clinical technologists in the Netherlands

Despite recent studies confirming task shifting is both safe and effective, its implementation has proven difficult in practice. So too in the Netherlands, where legal barriers enforcing strict professional boundaries have historically limited task shifting. In recent years, Dutch policymakers have experimented with temporary expanded scopes of practice (ESP) for several professional groups, with the aim to facilitate task shifting in order to increase the overall effectiveness and efficiency of health care. The Clinical Technologist (CT), is an emerging new professional group that has received such a temporary ESP pending an evaluation. This paper reports the qualitative findings of the implementation process of providing CTs with an temporary ESP. Data collection consisted of 69 semi-structured interviews, 3 focus group interviews and 9 participant observations, conducted between September 2015 and October 2017. Analysis was conducted through an ‘editing analysis style’ whereby data were categorized using the conceptual framework of Grol & Wensing’s implementation model. The study suggests that social features are of great importance when implementing task shifting. In situations with few social barriers, organizational and administrative barriers seem to be less dominant, thereby expediting the overall implementation process. Consequently, we recommend that policymakers should prioritize social features over organizational features when implementing task shifting.     

Comparison of two methodologies to analyze exposure to statins in an observational study on effectiveness

OBJECTIVE: Estimates of efficacy of drugs from clinical trials may differ from estimates in observational studies. To obtain valid results, the definition of exposure in an observational study is critical. The objective of our study was to compare different exposure definitions for assessing the effectiveness of statins. STUDY DESIGN AND SETTING: The study was performed in the Rotterdam Study, a population-based cohort study that included 7983 subjects of > or =55 years of age. We selected 3806 subjects who received antihyperlipidemic drug treatment (n=179) or had a total cholesterol > or =6.5 mmol/L at baseline. We conducted analyses with two different exposure definitions. RESULTS: Treatment with statins was assessed at baseline. The adjusted relative risk (RR) of myocardial infarction (MI) and stroke was 0.75 (95% confidence interval [CI] 0.41-1.37) and of total mortality was 1.34 (95% CI 0.66-2.74) in subjects treated with statins. We used pharmacy data, which give insight into drug use on a continuous basis. The adjusted RR of MI and stroke after 2 years of cumulative treatment was 0.63 (95% CI 0.34-1.15) and of total mortality was 0.91 (95% CI 0.59-1.39). CONCLUSION: Our results suggest that use of a time-dependent exposure definition is more accurate because estimates of effectiveness were more in agreement with results from randomized controlled trials of statin treatment.     

Assessment of large-vessel involvement in giant cell arteritis with 18F-FDG PET: introducing an ROC-analysis-based cutoff ratio

In the diagnosis of giant cell arteritis (GCA) with aortic involvement, (18)F-FDG PET has been demonstrated to be a powerful tool. No other imaging method is able to directly detect acute inflammation within the aortic wall. However, because GCA is a rare PET indication, the assessment of GCA with (18)F-FDG PET remains difficult and highly dependent on the experience of the investigator. This study aimed to semiquantify the relationship between aortic and liver uptake and to introduce a receiver operating characteristic (ROC)-based cutoff ratio to allow investigator- and experience-independent GCA diagnosis with optimal sensitivity and specificity. Ratios of aortic wall uptake versus liver uptake were calculated in a group of GCA patients and a control group. These data were assessed in an ROC analysis, and finally, a cutoff-ratio-optimizing strategy was applied. METHODS: Twenty-three patients with initially suspected GCA (18 positive for GCA criteria, 5 negative) and 36 matched controls were included. The control subjects underwent PET for oncologic diagnostics. None had intrathoracic or hepatic disease or therapy-related tracer accumulation. Additionally, physiologic liver metabolism was ensured by the presence of normal liver enzymes. After defining regions of interest over the thoracic aorta and the liver, we calculated maximal standardized uptake value ratios. Sensitivities and specificities for cutoff ratios from 0.1 to 2.5 were estimated and were ultimately used to assess an optimal cutoff ratio for separating GCA patients from controls. To further investigate the usefulness of the resulting cutoff ratio, we tested it in a second control group with changed hepatic metabolism and elevated liver enzymes. RESULTS: ROC analysis revealed optimal selectivity for a cutoff ratio of 1.0. This ratio led to a sensitivity of 88.9%, a specificity of 95.1%, and an accuracy of 94.4%. When this aorta-to-liver ratio was applied to the control group with pathologic liver metabolism, the resulting specificity was 95.6%. CONCLUSION: The (18)F-FDG PET region-of-interest analysis with aorta-to-liver maximal standardized uptake value ratios is a reliable, investigator-independent indicator of GCA not affected by minor inflammation-associated changes in hepatic metabolism. Our results for a cutoff ratio of 1.0 prove that (18)F-FDG PET is a method of high sensitivity and specificity for GCA-related large-vessel inflammation.     

Psychiatric comorbidity as a risk factor for the mortality of people with bulimia nervosa

Background

Bulimia nervosa (BN) is associated with increased mortality. Frequent comorbidities of BN include substance use disorders, affective disorders and personality disorders (PD). These comorbidities may add an additional risk for mortality.

Methods

We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders over an observation period from January 2007 to March 2016 for 1501 people with BN using anonymised health records data from the South London and Maudsley NHS Foundation Trust (SLaM), retrieved through its Clinical Records Interactive Search (CRIS) data resource. Mortality was ascertained through monthly linkages to the nationwide tracing system administered by the Office for National Statistics (ONS). We used Cox proportional hazards regression to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analyses were also performed to estimate effects when controlling for confounding of age, sex, ethnicity, borough, marital status and deprivation score.

Results

A total of 18 patients with BN died during the observation period. The standardised mortality ratio (SMR) for our study cohort (against the population of England and Wales in 2012 as a standard) was 2.52 (95% CI 1.49–3.97). Cox regressions revealed significant associations of mortality with older age and male gender. Comorbid PD (HR: 3.36; 95% CI 1.05–10.73) was significantly associated with all-cause mortality, even after controlling for demographic and socioeconomic covariates.

Conclusions

These results highlight increased mortality in patients with BN and the importance of recognising and treating PDs in patients with BN.

     

Evidence of a modality-dependent role of the cerebellum in working memory? An fMRI study comparing verbal and abstract n-back tasks

In working memory (WM), functional imaging studies demonstrate cerebellar involvement indicating a cognitive role of the cerebellum. These cognitive contributions were predominantly interpreted as part of the phonological loop within the Baddeley model of WM. However, those underlying investigations were performed in the context of visual verbal WM which could pose a bias when interpreting the results. The aim of this fMRI study was to address the question of whether the cerebellum supports additional aspects of WM in the context of higher cognitive functions. Furthermore, laterality effects were investigated to further disentangle the cerebellar role in the context of the phonological loop and the visuospatial sketchpad. A direct comparison of verbal and abstract visual WM was performed in 17 young volunteers by applying a 2-back paradigm and extracting the % change in BOLD signal from the fMRI data. To minimize potential verbal strategies, Attneave and Arnoult shapes of non-nameable objects were chosen for the abstract condition. The analyses revealed no significant differences in verbal vs. abstract WM. Moreover, no laterality effects were demonstrated in both verbal and abstract WM. These results provide further evidence of a broader cognitive involvement of the cerebellum in WM that is not only confined to the phonological loop but also supports central executive subfunctions. The fact that no lateralization effects are found might be attributed to the characteristics of the n-back paradigm which emphasizes central executive subfunctions over the subsidiary slave systems.     

Hypoglycemia Aggravates Critical Illness�CInduced Neurocognitive Dysfunction

OBJECTIVE

Tight glycemic control (TGC) in critically ill patients is associated with an increased risk of hypoglycemia. Whether those short episodes of hypoglycemia are associated with adverse morbidity and mortality is a matter of discussion. Using a case-control study design, we investigated whether hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients surviving critical illness.

RESEARCH DESIGN AND METHODS

From our patient data management system, we identified adult survivors treated for >72 h in our surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a history of neurocognitive dysfunction or structural brain abnormalities who experienced at least one episode of hypoglycemia during treatment (hypo group) (n = 37). For each hypo group patient, one patient stringently matched for demographic- and disease-related data were identified as a control subject. We performed a battery of neuropsychological tests investigating five areas of cognitive functioning in both groups at least 1 year after ICU discharge. Test results were compared with data from healthy control subjects and between groups.

RESULTS

Critical illness caused neurocognitive dysfunction in all tested domains in both groups. The dysfunction was aggravated in hypo group patients in one domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both hyperglycemia (r = −0.322; P = 0.005) and fluctuations of blood glucose (r = −0.309; P = 0.008) were associated with worse test results in this domain.

CONCLUSIONS

Hypoglycemia was found to aggravate critical illness–induced neurocognitive dysfunction to a limited, but significant, extent; however, an impact of hyperglycemia and fluctuations of blood glucose on neurocognitive function cannot be excluded.Since the concept of tight glycemic control (TGC) was introduced in critical care medicine in 2001 (1), its implementation in daily clinical practice has been the subject of a vivid discussion. Several single-center trials in different patient populations largely confirmed the clinical benefits, at least when patients were treated for a few days or longer in an intensive care unit (ICU) (2). Numerous studies have suggested plausible mechanisms behind the clinical benefits (3). However, a recent multicenter trial failed to confirm the strict blood glucose targets (4), and two multicenter trials have been preliminarily stopped because of a high incidence of hypoglycemic episodes (5).Indeed, hypoglycemia appears as the major side effect of any effort to regulate blood glucose levels with insulin, whatever the blood glucose levels aimed for (2). Although numerous algorithms are available to minimize this risk (6), the fear of hypoglycemia-induced mortality and permanent disability largely impedes the implementation of TGC in daily routine. Scientific evidence supporting the common notion that hypoglycemia is responsible for an increased mortality and profound permanent neurocognitive dysfunction rather than it being just a marker of severity of illness is poor and controversial, however. Efforts to substantiate any evidence are based on post hoc analyses, since confirmation from prospective randomized, controlled trials is precluded for obvious ethical reasons. Some studies imply that any mortality benefits of TGC might be outweighed when the incidence of hypoglycemia is very high (7); however, other analyses revealed conflicting results in this respect (8). Besides direct effects on mortality, neuroglycopenia might cause neuronal damage and at least subtle permanent neurocognitive impairment that potentially affects life quality after discharge. From diabetes, it is known that neuroglycopenia might have a permanent effect on neurocognitive function, at least when it occurs repetitively. Since diabetes and critical illness–induced dysregulations of glucose homeostasis represent substantially different entities, it is inappropriate to extrapolate these data to the ICU population. Cognitive impairment is a relevant problem of patients surviving critical illness in general (9). Currently, there are no data available on the specific impact of hypoglycemic events during treatment in ICU on long-term neurocognitive function. Using a case-control design, we investigated whether hypoglycemic episodes under TGC induce or aggravate permanent neurocognitive deficits in patients surviving critical illness.     

Pedaudiologic findings after severe neonatal hyperbilirubinemia

Neonatal hyperbilirubinemia (NHB) above 20 mg/dl (NHB20) has been shown to increase the risk of hearing impairments. Up to now, audiological findings based on behavioural audiometry (BA), otoacoustic emissions (TEOAE) and auditory brainstem responses (ABR) from children after being diagnosed with NHB20 have not been thoroughly compared to those with lower NHB-levels. We, therefore, aimed to assess the presence and characteristics of auditory dysfunction in children with NHB20. The audiological data of 15 children aged 11 months to 9 years with a NHB level between 22.6 and 45.6 mg/dl and/or MRI-confirmed bilirubin encephalopathy (NHBG) were compared retrospectively to 15 children with NHB levels between 12.5 and 19.4 mg/dl (CG). After matching by weeks of gestation at birth, BA, TEOAE and ABR were performed in all the children. Subsequently the groups were compared. Only two children of the NHBG had consistently normal audiologic findings. Hearing function disorders were detected in 87% (13/15) of the NHBG-children, ranging from total deafness to normal BA, including unilateral and bilateral deafness as well as cochlear hearing loss. Auditory neuropathy/dys-synchrony (AN) was found in a total of eight children (53%) of the NHBG. In addition, it was found that after the occurrence of NHB20, initially detected TEOAE can disappear in some cases. In the comparison group (CG) only two children demonstrated a hearing dysfunction, both of which were cochlear hearing impairments, whereas no child had AN. A bias towards hearing impairments has to be taken into account for both groups. Detailed pedaudiologic testing should be mandatory for all children after the occurrence of NHB20 including follow-up during the first 12 months. Audiological diagnostic work-up in the affected children requires objective investigations of hearing functions, while BA is recommended to evaluate the adequate therapeutic procedure. The data was partly presented as a lecture at the 78th Annual Meeting of the German Society of Otolaryngology—Head and Neck Surgery in Munich, Germany in May 2007, as well as at the 24th Annual Meeting of the German Society of Phoniatrics and Pedaudiology in Innsbruck, Austria, in September 2007.     

A preclinical study to investigate the development of nephrogenic systemic fibrosis: a possible role for gadolinium-based contrast media

OBJECTIVES: Several recent publications have suggested an association between the administration of gadolinium (Gd)-based contrast agents and the occurrence of Nephrogenic Systemic Fibrosis (NSF), an acquired disorder marked by skin thickening and fibrosis occurring in patients with severe renal dysfunction. The aim of this study was to establish a preclinical experimental setting to investigate the possible link between NSF and Gd-based contrast agents, and specifically the role of Gd and/or depletion of endogenous metal ions as possible triggers for NSF. MATERIALS AND METHODS: Thirty-five healthy male rats received repeated intravenous injections of Magnevist (gadopentetate dimeglumine; Gd-DTPA), Omniscan (gadodiamide; Gd-DTPA-BMA), or gadodiamide without caldiamide at a dose of 2.5 mmol Gd/kg body weight over at least 20 days to simulate the exposure to Gd-containing contrast agents in patients with severe renal dysfunction. In addition, caldiamide (the excess ligand in Omniscan) and Gd-ethylenediamine tetraacetic acid (Gd-EDTA) as a positive control, and saline as a negative control were studied. Histopathologic and immunohistochemical analysis of the skin was performed. Gd and zinc concentrations were measured in skin, femur, and liver tissue by atomic emission spectrometry. RESULTS: Rats receiving Gd-EDTA, gadodiamide without caldiamide, and Omniscan developed epidermal ulceration and acanthosis, dermo-epidermal clefts, minimal-to-slight dermal fibrosis, and increased dermal infiltration of different cells, partly positive for CD34 fibrocytes. No such NSF-like macroscopic lesions were observed in the saline, caldiamide, and Magnevist groups. High Gd concentrations in the skin were found in the Gd-EDTA, gadodiamide without caldiamide, and Omniscan groups. In the Magnevist group, Gd levels in the skin were 10-times lower than in the Omniscan-treated animals but elevated compared with saline. CONCLUSIONS: A preclinical experimental setting has been established where NSF-like lesions could be observed. The link between the application of Gd-based contrast media and the induction of NSF-like lesions was established. The data indicate that the observed skin lesions are related to the release of Gd and not to the depletion of endogenous ions. The investigations further suggest potential importance of the stability of Gd-based contrast agents.