Improving End of Life Cancer Outcomes Through Development and Implementation of a Spiritual Care Advocate Program.

BACKGROUND: Explored whether increased support for spiritual concerns between the healthcare team and patients through the provision of a Spiritual Care Advocate (SCA) would improve end of life outcomes in a metastatic cancer population. DESIGN: Newly diagnosed metastatic cancer patients were recruited at the University of Chicago Medical Center and received spiritual support from a Spiritual Care Advocate during chemotherapy treatments. The final sample consisted of 42 patients (58% of those approached) who completed the baseline survey and had known survival status. MEASUREMENT: Patients completed pre/post surveys measuring spiritual support and palliative quality of life. Baseline measurements of religious practice and externalizing religious health beliefs were also obtained. Receipt of aggressive EOL care was derived from the electronic medical record. RESULT: Median age was 61 years, with 48% Black, and predominantly male (62%). Of the 42 patients, 30 (70%) had died by the time of this analysis. Perceived spiritual support from the medical team increased in 47% of those who received non-aggressive EOL care and by 40% in those who received aggressive EOL care (p=0.012). Patient perceptions of spiritual support from the medical community increased from 27% at baseline to 63% (p=0.005) after the SCA intervention. Only 20% of recipients received aggressive treatments at end of life. CONCLUSION: The SCA model improved the perceived spiritual support between the healthcare team and patients. Although limited by a small sample size, the model was also associated with an improvement in EOL patients' quality of life, spiritual wellbeing, and decreased aggressive EOL care.

A comparison of prehospital lactate and systolic blood pressure for predicting the need for resuscitative care in trauma transported by ground.

BACKGROUND: Reliance on prehospital trauma triage guidelines misses patients with serious injury. Lactate is a biomarker capable of identifying high-risk trauma patients. Our objective was to compare prehospital point-of-care lactate (P-LAC) with systolic blood pressure (SBP) for predicting the need for resuscitative care (RC) in trauma patients transported by ground emergency medical services. METHODS: This is a prospective observational study at nine sites within the Resuscitation Outcomes Consortium conducted from March 2011 to August 2012. Lactate was measured on patients with a prehospital SBP of 100 mm Hg or less who were transported by emergency medical services to a Level I or II trauma center. Patients were followed up for the need for RC, defined as any of the following within 6 hours of emergency department arrival: blood transfusion of 5 U or greater; intervention for hemorrhage including thoracotomy, laparotomy, pelvic fixation, or interventional radiology embolization; or death. RESULTS: A total of 387 patients had a lactate value and presented with SBP between 71 mm Hg and 100 mm Hg, and 70 (18%) required RC. With the use of a P-LAC decision rule (≥2.5 mmol/L) that yielded the same specificity as that of SBP of 90 mm Hg or less (48%), the observed sensitivities for RC were 93% (95% confidence interval [CI], 84-98%) for P-LAC of 2.5 mmol/L or greater and 67% (95% CI, 55-78%) for SBP of 90 mm Hg or less (McNemar's test, p < 0.001). P-LAC has an estimated area under the curve of 0.78 (95% CI, 0.73-0.83), which is statistically superior to that of SBP (0.59; 95% CI, 0.53-0.66) and shock index (heart rate / SBP) (0.66; 95% CI, 0.60-0.74). CONCLUSION: P-LAC obtained at the scene is associated with the need for RC. P-LAC is superior to other early surrogates for hypoperfusion (SBP and shock index) in predicting the need for RC in trauma patients with 70 mm Hg < SBP ≤ 100 mm Hg. LEVEL OF EVIDENCE: Prognostic study, level II.

Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium.

OBJECTIVE: To identify causes and timing of mortality in trauma patients to determine targets for future studies. BACKGROUND: In trials conducted by the Resuscitation Outcomes Consortium in patients with traumatic hypovolemic shock (shock) or traumatic brain injury (TBI), hypertonic saline failed to improve survival. Selecting appropriate candidates is challenging. METHODS: Retrospective review of patients enrolled in multicenter, randomized trials performed from 2006 to 2009. Inclusion criteria were as follows: injured patients, age 15 years or more with hypovolemic shock [systolic blood pressure (SBP) ≤ 70 mm Hg or SBP 71-90 mm Hg with heart rate ≥ 108) or severe TBI [Glasgow Coma Score (GCS) ≤ 8]. Initial fluid administered was 250 mL of either 7.5% saline with 6% dextran 70, 7.5% saline or 0.9% saline. RESULTS: A total of 2061 subjects were enrolled (809 shock, 1252 TBI) and 571 (27.7%) died. Survivors were younger than nonsurvivors [30 (interquartile range 23) vs 42 (34)] and had a higher GCS, though similar hemodynamics. Most deaths occurred despite ongoing resuscitation. Forty-six percent of deaths in the TBI cohort were within 24 hours, compared with 82% in the shock cohort and 72% in the cohort with both shock and TBI. Median time to death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in patients with both. Sepsis and multiple organ dysfunction accounted for 2% of deaths. CONCLUSIONS: Most deaths from trauma with shock or TBI occur within 24 hours from hypovolemic shock or TBI. Novel resuscitation strategies should focus on early deaths, though prevention may have a greater impact.

The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.

The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL), T-prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated with defective apoptosis in response to alkylating agents and purine analogues. ATM mutant cells exhibit impaired DNA double strand break repair. Poly (ADP-ribose) polymerase (PARP) inhibition that imposes the requirement for DNA double strand break repair should selectively sensitize ATM-deficient tumor cells to killing. We investigated in vitro sensitivity to the poly (ADP-ribose) polymerase inhibitor olaparib (AZD2281) of 5 ATM mutant lymphoblastoid cell lines (LCL), an ATM mutant MCL cell line, an ATM knockdown PGA CLL cell line, and 9 ATM-deficient primary CLLs induced to cycle and observed differential killing compared with ATM wildtype counterparts. Pharmacologic inhibition of ATM and ATM knockdown confirmed the effect was ATM-dependent and mediated through mitotic catastrophe independently of apoptosis. A nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft model of an ATM mutant MCL cell line demonstrated significantly reduced tumor load and an increased survival of animals after olaparib treatment in vivo. Addition of olaparib sensitized ATM null tumor cells to DNA-damaging agents. We suggest that olaparib would be an appropriate agent for treating refractory ATM mutant lymphoid tumors.

Public knowledge and attitudes towards Human Papilloma Virus (HPV) vaccination.

BACKGROUND: Human Papilloma Virus (HPV) vaccine has undergone successful trials and has recently been approved for use for the primary prevention of cervical cancer. The aim of this study was to determine knowledge and attitudes towards HPV vaccination. METHODS: Semi-structured interview and questionnaire delivered in a street survey. Standardised HPV-related statements used to measure HPV knowledge and attitudes to vaccination. The setting was three different areas of Birmingham, to target a mix of social class and ethnicity. The sample population was composed of 16-54 year olds. RESULTS: A total of 420 participants were recruited. Poor knowledge of HPV and its links with cervical cancer were observed. 81% had a knowledge score of zero. Knowledge about HPV was associated with different ethnic group and socio-economic group. The majority (88%) of participants were in favour of vaccination, with 83.6% indicating that they would allow a child under their care to be vaccinated. CONCLUSION: Initial responses to the proposed HPV vaccination within the UK public are favourable. However, knowledge levels are poor and media and health professional promotion are required to raise awareness.

Multilocus loss of heterozygosity allelotypes identify a genetic pathway associated with progression from low to high stage disease in neuroblastoma.

Neuroblastoma is a heterogeneous tumour with a variety of clinical phenotypes, ranging from a localised tumour with excellent outcome (stage 1) to a metastatic, usually fatal malignancy (stage 4). In order to investigate the genetic relationship between these tumour subtypes, a loss of heterozygosity (LOH) analysis was carried out. Composite LOH allelotypes incorporating data from 96 loci on 5 chromosomes (1p, 3p, 4p, 11q, 14q), were constructed for 62 neuroblastomas. Neuroblastomas with similar allelotypes were clustered into groups and allelotype patterns correlated with clinical features. Three distinct genetic subgroups of neuroblastoma were observed. The largest group (50% of tumours) was characterised by specific allelotype patterns indicative of a stepwise accumulation of genetic alterations (11q LOH-->1p, 4p, and/or 14q LOH-->3p LOH), associated with progression from low to high stage disease. These tumours are distinct from MYCN amplified neuroblastomas which have a more rapid and aggressive disease course, and also a proportion of low stage tumours, often ganglioneuromas or ganglioneuroblastomas, with restricted growth potential.

Effect of surgical revascularization in patients with coronary artery disease and ventricular tachycardia or fibrillation in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry.

BACKGROUND: Patients who undergo resuscitation from near-fatal ventricular arrhythmias often have significant coronary artery disease, and revascularization has been shown to reduce myocardial ischemia and cardiac arrest episodes in this patient population. The magnitude of benefit attributed to revascularization has varied by study, and the use of adjunct implantable cardioverter defibrillator (ICD) therapy has not been well-characterized. METHODS AND RESULTS: The Antiarrhythmics Versus Implantable Defibrillators (AVID) registry included 3117 patients with life-threatening ventricular arrhythmias, of whom 2321 (77%) had documented coronary artery disease and 281 (17%) underwent a coronary artery bypass grafting revascularization procedure after the index event. Patients who underwent a revascularization procedure were younger, had a lower incidence rate of prior myocardial infarction and ventricular arrhythmia, had a higher left ventricular ejection fraction, had less congestive heart failure, and were more likely to have had ventricular fibrillation as the presenting arrhythmia. Patients who underwent revascularization had a better survival rate than did those who did not undergo such a procedure after the index event, and adjustment for differing baseline patient covariates did not alter the relative survival rate benefit. Further, ICD implantation offered a similar survival rate advantage to those patients in the AVID registry with coronary artery disease independent of revascularization. CONCLUSION: Coronary revascularization in the AVID registry patients with coronary artery disease effected a survival rate benefit that was not attributable to differences in baseline patient characteristics. The benefit of ICD on patient survival rate was not attenuated by a revascularization procedure.

Cost-effectiveness of the implantable cardioverter-defibrillator versus antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias: results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic analysis substudy.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) is an effective but expensive device. We used prospectively collected data from a large randomized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug (AAD) therapy, largely with amiodarone. METHODS AND RESULTS: Charges for initial and repeat hospitalizations, emergency room, and day surgery stays and the costs of antiarrhythmic drugs were collected on 1008 patients. Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients. Regression models were then created to attribute these expenses to the rest of the patients. Charges were converted to 1997 costs using standard methods. Costs and life years were discounted at 3% per year. Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness (C/E) ratio. Six-year, twenty-year, and lifetime C/E ratios were also estimated. At 3 years, total costs were $71 421 for a patient taking AADs and $85 522 for a patient using an ICD, and the ICD provided a 0.21-year survival benefit over AAD treatment. The base-case C/E ratio was thus $66 677 per year of life saved by the ICD compared with AAD therapy (95% CI, $30 761 to $154 768). Six- and 20-year C/E ratios remained stable between $68 000 and $80 000 per year of life saved. CONCLUSIONS: The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias, as judged from prospectively collected data in a randomized clinical trial.