The Impact of the Carer Support Needs Assessment Tool (CSNAT) in Community Palliative Care Using a Stepped Wedge Cluster Trial

Family caregiving towards the end-of-life entails considerable emotional, social, financial and physical costs for caregivers. Evidence suggests that good support can improve caregiver psychological outcomes. The primary aim of this study was to investigate the impact of using the carer support needs assessment tool (CSNAT), as an intervention to identify and address support needs in end of life home care, on family caregiver outcomes. A stepped wedge design was used to trial the CSNAT intervention in three bases of Silver Chain Hospice Care in Western Australia, 2012-14. The intervention consisted of at least two visits from nurses (2-3 weeks apart) to identify, review and address caregivers’ needs. The outcome measures for the intervention and control groups were caregiver strain and distress as measured by the Family Appraisal of Caregiving Questionnaire (FACQ-PC), caregiver mental and physical health as measured by SF-12v2, and caregiver workload as measured by extent of caregiver assistance with activities of daily living, at baseline and follow up. Total recruitment was 620. There was 45% attrition for each group between baseline and follow-up mainly due to patient deaths resulting in 322 caregivers completing the study (233 in the intervention group and 89 in the control group). At follow-up, the intervention group showed significant reduction in caregiver strain relative to controls, p=0.018, d=0.348 (95% CI 0.25 to 0.41). Priority support needs identified by caregivers included knowing what to expect in the future, having time for yourself in the day and dealing with your feelings and worries. Despite the challenges at the clinician, organisational and trial levels, the CSNAT intervention led to an improvement in caregiver strain. Effective implementation of an evidence-informed and caregiver-led tool represents a necessary step towards helping palliative care providers better assess and address caregiver needs, ensuring adequate family caregiver support and reduction in caregiver strain.     

Changes in cellular levels of inositol polyphosphates during apoptosis

Accumulations of higher inositol polyphosphates, diphosphoinositol polyphosphates or pyrophosphates, have been implicated to mediate cellular apoptosis. Whether cellular levels of lower inositol phosphates (lower than inositol hexakisphosphates) change during apoptosis is not known, although these inositol phosphates are known to play crucial roles in a number of cellular signaling processes including calcium mobilization. Therefore, in this study, we have examined changes in cellular levels of inositol phosphates following metabolic labeling of these compounds by [³H]myo-inositol and induction of apoptosis. The levels of inositol mono- and bis-phosphates were increased, whereas the levels of inositol tris- and tetrakis-phosphates decreased significantly with an increasing rate of apoptosis induced by etoposide in a dose-dependent manner. NaF treatment, which increased the rate of apoptosis in a time- and dose-dependent manner, also increased the levels of inositol mono- and bis-phosphates and drastically reduced the levels of inositol tris- and tetrakis-phosphates. Prior treatment with antimycin A, a strategy used to reverse the NaF-induced accumulations of higher InsPs, partially reduced the effects of NaF on apoptosis as well as the levels of lower InsPs. Taken together, our results suggest that cellular levels of lower InsPs are altered during apoptosis.     

Maintaining nitric oxide-induced airway relaxation with superoxide dismutase

BACKGROUND: We have previously shown that the protective effect of inhaled nitric oxide (iNO) against methacholine-induced bronchoconstriction is negated in airways subjected to hyperosmotic stress. In this study, hypothesizing that the impaired efficiency of iNO was caused by release of reactive oxygen radicals, we examined the effect of the radical scavenging enzyme superoxide dismutase (SOD). METHODS: Hemodynamic and respiratory measurements were performed on anesthetized rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80ppm), followed by MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4) pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F(2alpha) and for a marker of activation of COX-mediated inflammatory cascades, PGF(2alpha) metabolite. RESULTS: Pre-treatment with SOD restored the bronchoprotective response to iNO in hyperosmotic airways. No direct effect was seen by SOD treatment on levels of 8-iso-PGF(2alpha), but this marker of oxidative stress correlated positively with increased bronchoconstriction. Hyperosmotic challenge elevated levels of PGF(2alpha) metabolite, and pre-treatment with SOD protected against this activation of the inflammatory cascade. CONCLUSION: SOD pre-treatment restores the relaxant effects of iNO in hyperosmotically challenged airways by attenuating oxidative stress and activation of COX-mediated inflammatory cascades.     

Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation

Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F(2)-isoprostanes and prostaglandin F(2alpha), respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha) and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF(2alpha). PGF(2alpha) metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF(2a) were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F(2)-isoprostane.     

Spectral clustering for TRUS images

Background  

Identifying the location and the volume of the prostate is important for ultrasound-guided prostate brachytherapy. Prostate volume is also important for prostate cancer diagnosis. Manual outlining of the prostate border is able to determine the prostate volume accurately, however, it is time consuming and tedious. Therefore, a number of investigations have been devoted to designing algorithms that are suitable for segmenting the prostate boundary in ultrasound images. The most popular method is the deformable model (snakes), a method that involves designing an energy function and then optimizing this function. The snakes algorithm usually requires either an initial contour or some points on the prostate boundary to be estimated close enough to the original boundary which is considered a drawback to this powerful method.     

Oxidative stress and inflammatory response during and following coronary interventions for acute myocardial infarction

BACKGROUND: In acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), myocardial injury results from complex processes during both ischemia and reperfusion. Release of reactive oxygen species (ROS) may contribute to the accumulated myocardial damage. AIMS: To examine by frequent sampling of peripheral blood oxidative stress and early inflammation in patients undergoing primary PCI for AMI. Secondly, to assess whether a correlation exists between these parameters and the extent of myocardial damage. METHODS: Sixteen patients undergoing primary PCI within 6 h of AMI onset were included. Peripheral blood was sampled at start of procedure (t0) and repeatedly over 24 h following reperfusion. Main plasma analyses were: 8-iso-PGF2alpha (oxidative stress), 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); and troponin-T (myocardial injury). Additional analyses included: total antioxidant status (TAS); vitamins; hsCRP and lipids. RESULTS: 8-Iso-PGF2alpha increased following restoration of blood flow, returned to t0 values after 3 h and was reduced below t0 the following day. TAS decreased significantly from t0 to the next day. There was no significant correlation between 8-iso-PGF2alpha and troponin T values. 15-Keto-dihydro-PGF2alpha was elevated during the first hour. There was a major rise in hsCRP after 24 h. CONCLUSION: Following reperfusion by primary PCI in AMI, oxidative stress and an inflammatory response are induced immediately. A rise in 8-iso-PGF2a during ischemia indicate that ROS generation may also take place during severely reduced coronary blood flow and hypoxia. No direct relationship between 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha and troponin T was evident. The present study adds to the increasingly complex pathophysiological roles of ROS acting both as signal molecules and as mediators of tissue injury.     

Scar myofibroblasts of the infarcted rat heart express natriuretic peptides

The present study examined whether natriuretic peptide expression in the scar of post-myocardial infarcted (MI) rats was derived at least in part by residing myofibroblasts. ANP and BNP mRNA levels were significantly increased in the non-infarcted left ventricle and scar of 1-week post-MI male rats, as compared to the left ventricle of normal rats. The infarct region contained myofibroblasts and contracted cardiac myocytes residing predominantly in the epicardial border zone. In primary passage scar-derived myofibroblasts, alpha-myosin heavy chain mRNA was undetectable, whereas ANP, BNP, as well as adrenomedullin and corin mRNA expression persisted. In 1-3 day cultured primary passage myofibroblasts, prepro-ANP, mature ANP, and BNP staining was observed in the cytoplasm/perinuclear region co-incident with unorganized alpha-smooth muscle actin. Following 4-7 days in culture, myofibroblasts expressed organized alpha-smooth muscle actin filaments. However, natriuretic peptides were predominantly detected in the nucleus and cytoplasm, and thin filaments occupying the perinuclear region were positive for prepro-ANP and BNP. Isoproterenol treatment of first passage scar myofibroblasts increased protein synthesis and induced BNP mRNA expression, whereas ANP mRNA levels remained unchanged. By contrast, neither ANP nor BNP mRNAs were induced following exposure to AII despite increased protein synthesis. These data highlight the novel observation that scar myofibroblasts synthesized ANP, BNP, adrenomedullin, and expressed the pro-convertase corin. Constitutive and sympathetic-driven natriuretic peptide synthesis by myofibroblasts may in part influence reparative fibrosis.