A predictive model for survival after in-hospital cardiopulmonary arrest

BACKGROUND: In-hospital cardiopulmonary resuscitation (CPR) has seen a steady increase in the application of technology and techniques since the introduction of closed cardiac massage in 1960. Despite this progress, there has not been a demonstrated improvement in survival rates after in-hospital cardiac arrest over the last 40 years. Identification of prognostic factors associated with survival after a resuscitation attempt can help physician decisions and patients' end-of-life choices in a pre-arrest situation. METHODS: Using an Utstein-based template we analyzed 219 consecutive adult attempted resuscitations in a large urban teaching hospital over a 3-year period. The main outcome measures were survival to discharge, 1 and 3 months. Backwards stepwise logistic regression was used to select baseline variables that predict survival at discharge, 1 and 3 months. RESULTS: Survival rates at discharge, 1 and 3 months were 15.1, 13.3, and 11.5%. Meaningful neurological status (cerebral performance score of 1) at discharge was achieved in 61% of survivors. Independent predictors of survival were: higher body-mass index (BMI), presence of chronic renal insufficiency (CRI), respiratory arrest, ventricular tachycardia/fibrillation (VT/VF) as initial rhythm and arrest early during the hospital stay. A risk model based on these variables demonstrated a significant fit between predicted and observed survival at discharge with goodness of fit test P-value of 0.87. CONCLUSIONS: Survival after in-hospital cardiopulmonary arrest is poor and can be estimated by using clinical variables. If validated in a large prospective trial, this score could help physicians in attempting resuscitation, patients and families in making end-of-life decisions and hospitals in resource allocation.     

An audit of current practice and management of metastatic spinal cord compression at a regional cancer centre

Metastatic spinal cord compression (MSCC) is an oncological emergency requiring prompt recognition and management to preserve neurological function and mobility. We performed an audit to assess current practice of MSCC against current best practice as outlined by NICE. Our retrospective audit identified 10 patients from January to December 2009 with confirmed MSCC. The most common primary tumours were prostate 3 (30%), breast 3 (30%) and lung 2 (20%). Pain was the main presenting symptom 9 (90%), followed by weakness 7 (70%) and sensory changes 1 (10%). 5 (50%) had MRI within 24 hours and only 6 (60%) underwent full MRI scan. 8 (80%) had corticosteroids before MRI scan. 6 (60%) received radiotherapy within 24 hours. Only 4 (40%) were referred to orthopaedics and none of these patients had been recommended surgery. Up 14 days following radiological confirmation of MSCC, the number of patients who were unable to walk increased by 20%. Only 5 (50%) were discharged during this period of study. Our audit reported a number of variances in management compared to NICE guideline. These can be improved by following a'fast track' referral pathway and regular education for junior doctors and primary care doctors.     

Is inhibition of the renin–angiotensin system a new treatment option for Alzheimer's disease?

Findings from longitudinal and cross-sectional studies suggest an association between high blood pressure and dementia, and in turn the use of antihypertensives has been suggested to reduce incidence of dementia. Alzheimer's disease, the most common cause of dementia, is characterised in part by the deposition of amyloid beta protein (Abeta) in the brain. Reduction of Abeta load is now a major therapeutic strategy. In recent years the renin-angiotensin system, already of recognised importance in the pathogenesis of hypertension, has become a source of interest in the pathogenesis of Alzheimer's disease. This review explores molecular, genetic, and clinical studies that might help explain the relation between the renin-angiotensin system, hypertension, and Alzheimer's disease and whether treatment with angiotensin converting enzyme (ACE) inhibitors and similar treatment strategies have a part to play in the management of the disease.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

What are the qualitative experiences of people affected by kidney failure receiving haemodialysis?

Background

People affected by kidney failure receiving haemodialysis experience complexity within their health condition unlike any other chronic illness or condition. Kidney failure impacts the individual in all areas of their life including relationships and activities of daily living.

Objective

To conduct a meta-aggregation of studies about the lived experiences of people with kidney failure receiving haemodialysis.

Design

Using PRISMA Guidelines, six databases (CINAHL, ClinicalTrials.gov , Cochrane Library, MEDLINE, PsycINFO, and Scopus) were comprehensively searched using keywords and subject headings from January 1990 to October 2021. Articles were assessed according to prespecified eligibility criteria. Data extraction and quality appraisal was conducted. A meta-aggregation of qualitative findings was conducted using the Joanna Briggs Institute methodology for meta-aggregation.

Results

Of the 9409 articles screened, 55 studies were included. This represented a total of 188 findings across 45 categories representing a range of unmet supportive care needs. The meta-aggregation identified 11 synthesised findings broadly related to psychological/emotional needs, physical needs, social needs, interpersonal/intimacy needs, patient-clinician communication needs, family related needs, health system/information needs, spiritual needs, daily living needs, practical needs and daily living needs.

Conclusions

This meta-aggregation has identified that people affected by kidney failure can experience a range of unmet supportive care needs. It was evident that living with kidney failure and receiving haemodialysis impacted a person's sense of self, introduced practical needs and other complex needs which were not being addressed in existing services. This review has highlighted important implications for clinical practice and future research directions.     

MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer's disease

Matrix metalloproteinases (MMPs) -2, -3 and -9 are up-regulated in several cell types on exposure to amyloid β peptide (Aβ) and have Aβ-degrading activity in vitro . The aims of this study were to determine (i) the distribution of MMP-2, -3 and -9 in the cerebral cortex in Alzheimer's disease (AD) and control brains; (ii) whether the levels and activity of these proteases are increased in AD; and (iii) whether their activity is related to Aβ load. In addition, we examined whether promoter polymorphisms in the MMP-3 and -9 genes are associated with AD in the study cohort. Paraffin sections of frontal lobe from AD and control cases were immunostained for MMP-2, -3 and -9 and tissue homogenates used for MMP activity assays. DNA from these cases was genotyped for the MMP-3 5A/6A (-1171) and MMP-9 C-1562T promoter polymorphisms. Immunohistochemistry revealed MMP-3 in plaques and both MMP-3 and -9 around scattered neurones. The levels and activity of all three MMPs were similar in AD and control brains and bore no relationship to Aβ load. Analysis of MMP-3 -1171 5A/6A allele frequencies showed that the 6A allele (with reduced promoter activity) was associated with AD; the MMP-9 C-1562T polymorphism was not. The levels and activities of MMP-2, -3 and -9 are not increased in the frontal cortex in AD and are not related to Aβ load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of Aβ in AD.