Abusive head trauma in court: a multi-center study on criminal proceedings in Germany

International Journal of Legal Medicine - The shaken baby syndrome (SBS) is a common variant of abusive head trauma (AHT) in infants and toddlers. Data on the legal outcome of such cases are still...     

Maximizing the Value of Mobile Health Monitoring by Avoiding Redundant Patient Reports: Prediction of Depression-Related Symptoms and Adherence Problems in Automated Health Assessment Services

Background

Interactive voice response (IVR) calls enhance health systems’ ability to identify health risk factors, thereby enabling targeted clinical follow-up. However, redundant assessments may increase patient dropout and represent a lost opportunity to collect more clinically useful data.

Objective

We determined the extent to which previous IVR assessments predicted subsequent responses among patients with depression diagnoses, potentially obviating the need to repeatedly collect the same information. We also evaluated whether frequent (ie, weekly) IVR assessment attempts were significantly more predictive of patients’ subsequent reports than information collected biweekly or monthly.

Methods

Using data from 1050 IVR assessments for 208 patients with depression diagnoses, we examined the predictability of four IVR-reported outcomes: moderate/severe depressive symptoms (score ≥10 on the PHQ-9), fair/poor general health, poor antidepressant adherence, and days in bed due to poor mental health. We used logistic models with training and test samples to predict patients’ IVR responses based on their five most recent weekly, biweekly, and monthly assessment attempts. The marginal benefit of more frequent assessments was evaluated based on Receiver Operator Characteristic (ROC) curves and statistical comparisons of the area under the curves (AUC).

Results

Patients’ reports about their depressive symptoms and perceived health status were highly predictable based on prior assessment responses. For models predicting moderate/severe depression, the AUC was 0.91 (95% CI 0.89-0.93) when assuming weekly assessment attempts and only slightly less when assuming biweekly assessments (AUC: 0.89; CI 0.87-0.91) or monthly attempts (AUC: 0.89; CI 0.86-0.91). The AUC for models predicting reports of fair/poor health status was similar when weekly assessments were compared with those occurring biweekly (P value for the difference=.11) or monthly (P=.81). Reports of medication adherence problems and days in bed were somewhat less predictable but also showed small differences between assessments attempted weekly, biweekly, and monthly.

Conclusions

The technical feasibility of gathering high frequency health data via IVR may in some instances exceed the clinical benefit of doing so. Predictive analytics could make data gathering more efficient with negligible loss in effectiveness. In particular, weekly or biweekly depressive symptom reports may provide little marginal information regarding how the person is doing relative to collecting that information monthly. The next generation of automated health assessment services should use data mining techniques to avoid redundant assessments and should gather data at the frequency that maximizes the value of the information collected.     

Atraumatic Pulsatile Leukocyte Circulation for Long‐Term In Vitro Dynamic Culture and Adhesion Assays

Low flow rate pumping of cell suspensions finds current applications in bioreactors for short‐term dynamic cell culture and adhesion assays. The aim of this study was to develop an atraumatic pump and hemodynamically adapted test circuit to allow operating periods of at least several hours. A computer‐controlled mini‐pump (MP) was constructed based on non‐occlusive local compression of an elastic tube with commercial bi‐leaflet valves directing the pulsatile flow into a compliant circuit. Cell damage and activation in the system were tested with whole blood in comparison with a set with a conventional peristaltic pump (PP). Activation of circulating THP‐1 monocytes was tested by measuring the expression of CD54 (ICAM‐1). Additionally, monocyte‐endothelial interactions were monitored using a parallel‐plate flow chamber with an artificial stenosis. The system required a priming volume of only 20 mL, delivering a peak pulsatile flow of up to 35 mL/min. After 8 h, blood hemolysis was significantly lower for MP with 11 ± 3 mg/dL compared with PP with 100 ± 16 mg/dL. CD142 (tissue factor) expression on blood monocytes was 50% lower for MP. With MP, THP‐1 cells could be pumped for extended periods (17 h), with no enhanced expression of CD54 permitting the long‐term co‐culture of THP‐1 with endothelial cells and the analysis of flow pattern effects on cell adhesion. A low‐damage assay setup was developed, which allows the pulsatile flow of THP‐1 cells and investigation of their interaction with other cells or surfaces for extended periods of time.     

Storage of platelet concentrates using ion exchange resin charged with dibasic phosphate.

Platelet concentrates were prepared at twice the normal concentration and stored at room temperature for 7 days in either standard bags (controls) or bags to which 1 or 2 g of Amberlite resin beads charged with dibasic phosphate had been added. The resin beads served as a buffer system by providing a "slow release" form of phosphate ions as well as by binding CO2 produced during platelet metabolism. Control platelets demonstrated rapid falls in pH, ATP content, morphology score, and thrombin-induced nucleotide release after 24 hr of storage with a fall in pH to less than 6.0 by day 3. Profound ultrastructural changes and a rise in pO2, suggesting loss of platelet viability, accompanied these changes. In contrast, the resin-stored platelets remained near normal after 24 hr of storage, with preservation of discoid morphology, 95% of ATP levels, excellent ultrastructural appearance, and evidence of continued oxygen consumption after 3 days of storage. Even after 7 days of storage, ATP levels remained greater than 50% of baseline and ultrastructurally intact platelets were seen. In the 1-g resin bags the pH remained at baseline levels (6.9-7.0), while there was a rise in pH in the 2-g resin bags. These results demonstrate the beneficial effects of maintaining a higher pH during platelet storage and provide a new approach to studying the metabolic changes that occur during longer term storage.     

The effect of biguanides on secretion and biosynthesis of insulin in isolated pancreatic islets of rats

Summary Based on the clinical observation that biguanide treatment of obese patients may alter insulin levels, the influence of metformin and phenformin on basal and glucose stimulated insulin secretion, as well as on insulin biosynthesis, was studied in isolated islets of rats. — Biguanide concentrations of 100 g/ml, or higher, significantly reduced glucose stimulated insulin secretion. Both dose dependence and a difference in the intrinsic activities of metformin and phenformin were demonstrated. Incubating the same islets for a second period without biguanides, glucose stimulated insulin secretion was still decreased. Addition of glibenclamide during this second period increased insulin secretion, but did not overcome complete inhibition achieved after incubation at very high biguanide concentrations. Glucose stimulated biosynthesis of proinsulin and insulin was decreased in the presence of biguanides and completely suppressed at very high concentrations. Inhibition of cell respiration in the islet cells effected by high biguanide doses may be the reason for the inhibition of secretion and biosynthesis of insulin. — On the other hand, an insulin release was found at the highest phenformin concentration of 10 mg/ ml and during perfusion of the isolated rat pancreas with higher biguanide doses. — Biguanide concentrations found to be effective in this study are very high compared with therapeutic levels. Moreover, biguanide actions are known to be highly dependent on species, concentration and metabolic situation. — Definite conclusions from these findings regarding clinical significance, therefore, seem unwarranted.Supported by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg.     

Central kappa- and mu-opiate receptors mediate ACTH-release in rats

The control of ACTH secretion by opiates seems to involve stimulatory and inhibitory pathways, since opiate agonists and antagonists are capable of releasing ACTH in conscious rats. To elucidate the role of different opiate receptors in the control of ACTH release, rats were treated with receptor-selective opiate agonists and antagonists. The mu-opiate agonists, morphine and (D-Ala2, MePhe4, Gly5-ol)enkephalin, and the benzomorphan kappa-opiate agonists, MR 2034 and MRZ 2549, both stimulated ACTH release after central or peripheral injection. The effects of morphine, but not those of MR 2034, were blocked by a low dose of naloxone (50 micrograms/kg) and by the mu-receptor antagonist, beta-funaltrexamine. A 20 times higher dose of naloxone also blocked the effects of the kappa-agonist. Our data suggest that both mu- and kappa-opiate receptors are involved in the stimulation of ACTH release in rats.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.