Caregiving burden of families looking after persons with intellectual disability and behavioural or psychiatric problems

Background During the last decade, there has been a growing interest in outpatient support services for persons with intellectual disability (ID) and psychiatric and/or behavioural problems and their families. In this study, we explore the family burden that is associated with children or adults with ID and behavioural or psychiatric problems living at home. Method The research group consisted of 66 clients of In Casa, a project of outpatient treatment. Their average age is 18.97 years and their average IQ 55.37. The Reiss Screen for Maladaptive Behaviour (adults) or Reiss Scales for Children's Dual Diagnosis (children) and the Nijmegen Family Situation Questionnaire have been administered. Results About 62% of the children and 86% of the adults living at home and referred to In Casa have severe psychiatric or behavioural problems as measured by the Reiss scales. The dual diagnosis has a more negative impact on the family situation than the condition of ID only. Conclusion Parents consider the psychiatric or behavioural problems of their child to be an extra burden and feel it more difficult to raise and manage such a child. This impels them to change the situation and to call on the help of external services. Some methodological questions and the implications of the findings in terms of support needs are discussed.     

Sexual interactions between estrous female rats and castrated male rats treated with testosterone propionate or estradiol benzoate

Estrous female rats display 'precopulatory behaviors' such as ear wiggling and hopping/darting when castrated males treated with testosterone propionate (TP) are placed in their vicinity and before copulatory interactions have taken place. Castrated males treated with estradiol benzoate (EB) do not elicit these precopulatory behaviors in advance of copulatory interactions. It therefore seemed of interest to study females' sexual behavior with castrated males treated with TP or EB when males or females had primary control over the temporal patterning of the behavior. Unrestrained sexual behavior (= male control) with EB-treated males was characterized by large numbers of intromissions and long periods of time preceding ejaculation, as compared with interactions with TP-treated males. The temporal pattern of sexual behavior did not change importantly when the males were tethered (= sexual behavior controlled by females). When given a choice between two sexually active castrated and tethered males, one treated with TP and the other with EB, estrous females 'preferred' EB-treated animals in various respects. Fewer interactions occurred with, and less time was spent in the vicinity of, TP-treated males over prolonged observation periods (115-135 min). The preference for EB-treated males disappeared, and TP- and EB-treated animals became equally attractive, when the vaginal opening of the female animals was covered with adhesive tape to prevent the occurrence of penile intromissions during mounting. It is concluded that female control over copulatory behavior does not necessarily change the females' sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)     

CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

Background  

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.     

Occupancy of adenosine receptors on human neutrophils inhibits respiratory burst stimulated by ingestion of complement-coated particles and occupancy of chemoattractant but not Fc receptors

Chemoattractants are generated at inflammatory loci that not only induce neutrophils (PMNs) to leave the vasculature but also stimulate PMNs to release potentially toxic agents (e.g., H₂O₂, O ₂ ^– or OH). We have recently demonstrated that endothelium releases adenosine which, when bound to a specific receptor on the PMN surface, inhibits release of toxic oxygen metabolites from stimulated PMN. To determine whether occupancy of adenosine receptors modulates generation and release of oxygen metabolites, we have studied the effect of 2-chloroadenosine on O ₂ ^– generation and O₂ consumption in response to opsonized zymosan particles (STZ) and immune complexes (IC). 2-Chloroadenosine inhibits, in a dose-dependent fashion, Of generation by neutrophils that have been exposed to C3b-coated particles (STZ). Inhibition of Of generation is similar in the presence or absence of cytochalasin B (IC₅₀=53 ±19 and 16 ±5nM, respectively,P=NS). Since occupancy of adenosine receptors might inhibit only externalization but not generation of oxygen metabolites, we studied the effect of 2-chloroadenosine on oxygen consumption by activated neutrophils. 2-Chloroadenosine inhibited O₂ consumption stimulated by STZ and the surrogate bacterial chemoattractant FMLP; however, inhibition of O₂ consumption varied with the presence or absence of cytochalasin B. In contrast, when neutrophils were stimulated by immune complexes, 2-chloroadenosine only minimally inhibited O ₂ ^– release and O₂ consumption (10 ± 5 and 5 ± 4% inhibition, respectively). Thus, occupancy of adenosine receptors inhibits O₂ consumption in parallel with inhibition of O ₂ ^– release. These results support the hypothesis that ingestion of complement-opsonized particles stimulates the respiratory burst by a mechanism different from that by which the respiratory burst is stimulated after occupancy of Fc receptors. Moreover, these observations suggest that endothelium, by releasing adenosine, prevent activated neutrophils from damaging the microvasculature at inflammatory loci. In contrast, deposition of immune complexes in vessel walls leads to vascular damage because endothelial cells are incapable of preventing attack by immune complex-stimulated neutrophils.This research was supported by grants from the U.S. Public Health Service (AI-10343 and HL29034) and the Veterans Administration.Dr. Cronstein is the recipient of a Clinical Investigator Award (K11-AR-01490) and was a fellow of the Arthritis Foundation. Dr. Broekman was an Established Investigator of the American Heart Association.     

Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.

     

The role of ethnicity and socioeconomic status in Southeast Asian mothers’ parenting sensitivity

Past research indicates that socioeconomic status (SES) accounts for differences in sensitivity across ethnic groups. However, comparatively little work has been conducted in Asia, with none examining whether ethnicity moderates the relation between SES and sensitivity. We assessed parenting behavior in 293 Singaporean citizen mothers of 6-month olds (153 Chinese, 108 Malay, 32 Indian) via the Maternal Behavioral Q-Sort for video interactions. When entered into the same model, SES (F(1,288) = 17.777, p < .001), but not ethnicity, predicted maternal sensitivity (F(2,288) = .542, p = .582). However, this positive relation between SES and sensitivity was marginally moderated by ethnicity. SES significantly positively predicted sensitivity in Chinese, but not Malay dyads. Within Indian dyads, SES marginally positively predicted sensitivity only when permanent residents were included in analyses. We discuss the importance of culture on perceived SES-associated stress. However, because few university-educated Malays participated, we also consider whether university education, specifically, positively influences sensitivity.     

Effects of SolCD39, a Novel Inhibitor of Platelet Aggregation,on Platelet Deposition and Aggregation after PTCA in a Porcine Model

Introduction: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP.Methods and Results: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5–7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by > 90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7 ± 1.4 versus 11.7 ± 3.4) and fibrin (3.5 ± 0.4 versus 4.2 ± 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP_SFLLRN) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel.Conclusions: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study.Abbreviated Abstract. E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5–7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.Supported in part by a Merit Review grant from the Department of Veterans Affairs (A.J.M., M.J.B.), and by National Institutes of Health grants HL 47073, HL 46403, and NS 41462 (A.J.M., M.J.B.) and by Immunex Corp., Seattle, WA.     

Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study

Purpose

Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown.

Methods

Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed.

Results

Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay.

Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5?±?14.8 years), had a median MD of???5.3 decibel (IQR???3.1 to???10.1). MD was strongly correlated with clinical severity (r?=????0.94, P?<?0.0001), and were used for severity of defects cut-off values: (1) normal?>????2 dB, (2) mild???2 dB to???4 dB, (3) moderate???4 to???8 dB, (4) severe???8 to???17 dB, (5) very severe?<????17 dB.

Conclusion

Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.