Publications

Hospitals do not routinely collect data about homelessness. The objectives of the present study were to (1) describe rate of patient reports of homelessness among inpatients at a public hospital, (2) assess the agreement between patient report of housing status on a study questionnaire with clinical and administrative data about homelessness, and (3) assess changes in housing status during hospitalization. We conducted a cross-sectional survey of inpatients at an urban public hospital to assess housing status; we then examined subjects' medical charts to assess agreement with the questionnaire on housing status. Of inpatients, 25.6% were homeless at discharge. An additional 19.4% were marginally housed. One third of homeless persons had their housing status change during their hospitalization. Administrative data identified 25.6% and physicians' notes identified 22.5% as homeless. Clinical, administrative, and survey data did not agree. Homelessness and changes in housing status are common among inpatients at an urban public hospital. Poor agreement on who is homeless limits the usefulness of data.

BACKGROUND

Screening mammography for women 50 to 69 years of age may lead to 50% having an abnormal study. We set out to determine the proportion of women who understand their abnormal mammogram results and the factors that predict understanding.

METHODS

We surveyed 970 women age 40 to 80 years identified with abnormal mammograms from 4 clinical sites. We collected information on demographic factors, language of interview, consultation with a primary care physician, receipt of follow-up tests, and method of notification of index mammogram result. This study examines the following outcomes: the participant's report of understanding of her physician's explanation of results of the index mammogram, and a comparison of the radiology report to the participant's report of her index mammogram result. Multivariate models controlled for age, education, income, insurance status, and clinical site.

RESULTS

The majority (70%) reported a "full understanding" of their physician's explanation of their abnormal mammogram, but a significant minority (30%) reported less than a full understanding (somewhat, not at all, did not explain). Among women of Asian ethnicity, only 63% reported full understanding. Asian ethnicity was a negative predictor (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3 to 0.7), and consultation with a primary care physician was a positive predictor (OR, 2.3; 95% CI, 1.7 to 3.3) of reported full understanding. Of the 304 women with a suspicious abnormality, only 51% understood their result to be abnormal. Women notified in person or by telephone were more likely than women notified in writing to understand their result to be abnormal (OR, 2.3; 95% CI, 1.2 to 4.8).

CONCLUSION

Almost half of women with the most suspicious mammograms did not understand that their result was abnormal. Our data suggest that direct communication with a clinician in person or by phone improves comprehension.

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.

The renin-angiotensin system (RAS) is a strong candidate as a mediator for the development and progression of lupus nephritis (LN). We performed an ethnically stratified analysis of 642 systemic lupus erythematosus (SLE) patients to determine whether various functional RAS gene polymorphisms are associated with SLE renal outcomes. Patients were genotyped for two angiotensin-converting enzyme (ACE) gene polymorphisms: Alu insertion/deletion (I/D) and 23 949 (CT)(2/3), and for two angiotensinogen (Atg) gene polymorphisms: M235T and C-532T. Multivariate analyses demonstrated associations between the ACE I/D, ACE (CT)(2/3) and Atg C-532T functional polymorphisms and LN among Asians. In stratified analyses among LN cases according to high vs low glomerular filtration rate (GFR), associations remained significant for the ACE D (odds ratio (OR) 5.9, P=0.001) and (CT)(2) (OR 6.2, P=0.001) alleles among Asian subjects with low GFR. Lastly, we found allelic dose-dependent associations between the ACE I/D (P=0.003), ACE (CT)(2/3) (P=0.005) and Atg M235T (P=0.04) polymorphisms, and GFR analyzed as a continuous variable among Asians. These findings suggest a significant role for ACE and Atg gene sequence variation and severity of LN among Asians with SLE.

We recently reported that hyperalgesia induced by the inflammatory mediator prostaglandin E(2) (PGE(2)) requires intact alpha1, alpha3 and beta1 integrin subunit function, whereas epinephrine-induced hyperalgesia depends on alpha5 and beta1. PGE(2)-induced hyperalgesia is mediated by protein kinase A (PKA), while epinephrine-induced hyperalgesia is mediated by a combination of PKA, protein kinase Cepsilon (PKCepsilon) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We hypothesized that inflammatory mediator-induced hyperalgesia involves specific interactions between different subsets of integrin subunits and particular second messenger species. In the present study, function-blocking anti-integrin antibodies and antisense oligodeoxynucleotides were used to elucidate these interactions in rat. Hyperalgesia produced by an activator of adenylate cyclase (forskolin) depended on alpha1, alpha3 and beta1 integrins. However, hyperalgesia induced by activation of the cascade at a point farther downstream (by cAMP analog or PKA catalytic subunit) was independent of any integrins tested. In contrast, hyperalgesia induced by a specific PKCepsilon agonist depended only on alpha5 and beta1 integrins. Hyperalgesia induced by agonism of MAPK/ERK depended on all four integrin subunits tested (alpha1, alpha3, alpha5 and beta1). Finally, disruption of lipid rafts antagonized hyperalgesia induced by PGE(2) and by forskolin, but not that induced by epinephrine. Furthermore, alpha1 integrin, but not alpha5, was present in detergent-resistant membrane fractions (which retain lipid raft components). These observations suggest that integrins play a critical role in inflammatory pain by interacting with components of second messenger cascades that mediate inflammatory hyperalgesia, and that such interaction with the PGE(2)-activated pathway may be organized by lipid rafts.

Histone acetylation and deacetylation are crucial in the regulation of gene expression. Dynamic changes in gene expression may affect chromatin structure and, consequently, the interaction of chromatin with regulatory factors. In this study, the effects of the antiseizure drug valproic acid (VPA) on the expression of genes that regulate the structure of chromatin and the access of macromolecules to the DNA were investigated. Exposure of breast cancer cells to VPA resulted in rapid dose-dependent hyperacetylation of the histones H3 and H4. VPA further induced a depletion of several members of the structural maintenance of chromatin (SMC) proteins, SMC-associated proteins, DNA methyltransferase, and heterochromatin proteins. Down-regulation of these proteins was associated with chromatin decondensation. The observed alterations of chromatin structure correlated with enhanced sensitivity of DNA to nucleases and increased interaction of DNA with intercalating agents. VPA-induced chromatin decondensation led to a sequence-specific potentiation of DNA-damaging agents in cell culture and xenograft models. Modulation of heterochromatin maintenance proteins was not a direct, but a downstream, effect of histone acetylation. The effects on the chromatin structure were reversible upon drug withdrawal, but obligatory for the potentiation of DNA-damaging agents. In addition to their antitumor activity as single agents, the chromatin decondensation induced by histone deacetylase inhibitors may enhance the efficacy of cytotoxic agents that act by targeting DNA. The proposed mechanism of action suggests an effect of drug sequencing on the antitumor activity of these drugs.