Religiously affiliated intensive care unit patients receive more aggressive end-of-life care

Background

Previous studies among cancer patients have demonstrated that religious patients receive more aggressive end-of-life (EOL) care. We sought to examine the effect of religious affiliation on EOL care in the intensive care unit (ICU) setting.

Materials and methods

We conducted a retrospective review of all patients admitted to any adult ICU at a tertiary academic center in 2010 requiring at least 2 d of mechanical ventilation. EOL patients were those who died within 30 d of admission. Hospital charges, ventilator days, hospital days, and days until death were used as proxies for intensity of care among the EOL patients. Multivariate analysis using multiple linear regression, zero-truncated negative binomial regression, and Cox proportional hazard model were used.

Results

A total of 2013 patients met inclusion criteria; of which, 1355 (67%) affirmed a religious affiliation. The EOL group had 334 patients, with 235 (70%) affirming a religious affiliation. The affiliated and nonaffiliated patients had similar levels of acuity. Controlling for demographic and medical confounders, religiously affiliated patients in the EOL group incurred 23% (P = 0.030) more hospital charges, 25% (P = 0.035) more ventilator days, 23% (P = 0.045) more hospital days, and 30% (P = 0.036) longer time until death than their nonaffiliated counterparts. Among all included patients, survival did not differ significantly among affiliated and nonaffiliated patients (log-rank test P = 0.317), neither was religious affiliation associated with a difference in survival on multivariate analysis (hazard ratio of death for religious versus nonreligious patients 0.95, P = 0.542).

Conclusions

Compared with nonaffiliated patients, religiously affiliated patients receive more aggressive EOL care in the ICU. However, this high-intensity care does not translate into any significant difference in survival.     

Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy

Zidovudine (3-azido-3'-deoxythymidine), also referred to as azidothymidine (AZT), has become an integral component in highly active antiretroviral therapy, and has also been used in the treatment of cancer. The clinical effectiveness of AZT is constrained due to its association with increased adverse effects, such as myopathy. There are numerous potential mechanisms that may contribute to AZT-induced myopathy. The first hypothesized mechanism to explain AZT-induced toxicity was mtDNA depletion due to inhibition of DNA polymerase gamma. Although mtDNA depletion is present in patients with myopathy, current data suggests that alternative mechanisms may play a more direct role in the myotoxicity. These mechanisms include AZT-induced oxidative stress, direct inhibition of mitochondrial bioenergetic machinery, and mitochondrial depletion of L-carnitine. Furthermore, we hypothesize that apoptosis may play a role in AZT-induced myopathy.     

Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome

At least one-third of patients meeting clinical criteria for Lynch syndrome will have no germline mutation and constitutional epimutations leading to promoter methylation of MLH1 have been identified in a subset of these patients. We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next generation sequencing panel of 29 genes also failed to identify a pathogenic mutation. Hypermethylation was identified in MLH1 intron 1 in tumor specimens along with buccal cells and peripheral white blood cells, confirming the diagnosis of constitutional MLH1 promoter methylation. This case highlights that constitutional MLH1 methylation should be considered in the differential diagnosis for a polyposis syndrome if IHC staining shows absent MMR gene expression.     

Multiple informant agreement and the anxiety disorders interview schedule for parents and children

OBJECTIVE: To examine concordance of child, parent, and consensus agreement on the Anxiety Disorders Interview Schedule, Child and Parent versions (ADIS-C/P), for an outpatient sample of children and adolescents and to explore moderators of those relations. Child characteristics (age, gender, social desirability), a family environment variable (conflict), and type of diagnoses (internalizing, externalizing) were systematically examined. METHOD: These relations were examined in 165 children and adolescents referred to a psychological clinic by family practitioners, pediatricians, schools, and mental health professionals. Participants were individually administered the ADIS-C or ADIS-P by separate clinicians, and consensus diagnoses were determined in a clinical conference. Agreements between child-parent, child-consensus, and parent-consensus were determined. RESULTS: Poor levels of agreement were found among our informants, especially between child and parent and to some extent between child and consensus. Agreement was higher between parent and consensus, suggesting that our clinicians tended to favor parent input over child input. Although the effects were complex, characteristics of the child, family, and type of diagnosis moderated or qualified these findings. CONCLUSIONS: Although discrepancies exist among our informants, our overall findings suggest important information is obtained from each informant and, when combined with certain modifying characteristics, may lead to diagnostic and treatment decisions.     

Interferon-β gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice

Despite the potential of type 1 interferons (IFNs) for the treatment of cancer, clinical experience with IFN protein therapy of solid tumors has been disappointing. IFN-β has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. The antiproliferative effect, however, relies on IFN-β concentrations that cannot be achieved by parenteral protein administration because of rapid protein clearance and systemic toxicities. We demonstrate here that ex vivo IFN-β gene transduction by a replication-defective adenovirus in as few as 1% of implanted cells blocked tumor formation. Direct in vivo IFN-β gene delivery into established tumors generated high local concentrations of IFN-β, inhibited tumor growth, and in many cases caused complete tumor regression. Because the mice were immune-deficient, it is likely that the anti-tumor effect was primarily through direct inhibition of tumor cell proliferation and survival. Based on these studies, we argue that local IFN-β gene therapy with replication-defective adenoviral vectors might be an effective treatment for some solid tumors.