Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005.

Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C(hi)/Ly-6C(lo)) and human (CD14(hi)/CD14(lo)CD16(+)) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C(hi) monocyte responses while sparing Ly-6Clo monocyte activity.

OBJECTIVE

This study compared the effects of immediate (ICC) and delayed (DCC) cord clamping on very low birth weight (VLBW) infants on 2 primary variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC). Other outcome variables were late-onset sepsis (LOS) and intraventricular hemorrhage (IVH).

METHODS

This was a randomized, controlled unmasked trial in which women in labor with singleton fetuses <32 weeks' gestation were randomly assigned to ICC (cord clamped at 5-10 seconds) or DCC (30-45 seconds) groups. Women were excluded for the following reasons: their obstetrician refused to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa, or rapid delivery after admission.

RESULTS

Seventy-two mother/infant pairs were randomized. Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in maternal and infant demographic, clinical, and safety variables. There were no differences in the incidence of our primary outcomes (BPD and suspected NEC). However, significant differences were found between the ICC and DCC groups in the rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus 8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There was a trend toward higher initial hematocrit in the infants in the DCC group.

CONCLUSIONS

Delayed cord clamping seems to protect VLBW infants from IVH and LOS, especially for male infants.

OBJECTIVE

Our goal in this study was to evaluate by means of MRI the clinical significance of tendon integrity, muscle fatty degeneration, and muscle atrophy in surgically repaired massive rotator cuff tears and to correlate these and other prognostic factors with intraoperative and clinical findings.

METHODS

Twenty-eight surgically proven massive rotator cuff tears were retrospectively included in the study. Twenty-two patients underwent complete repair, and six patients underwent partial repair. Preoperative and postoperative clinical assessment was performed by using the University of California at Los Angeles score. Preoperative and postoperative MRI studies were evaluated for the presence and extent of rotator cuff tear and for the degree of fatty degeneration and atrophy of the rotator cuff muscles.

RESULTS

At a mean 44.4 months' follow-up, 20 patients (71.4%) had a favorable result. A total of 25 patients (89.2%) showed postoperative full-thickness rotator cuff tear, 19 of which were reruptures. A sagittal preoperative rotator cuff tear of less than or equal to 34 mm showed a specificity of 100% for predicting a favorable outcome. A coronal postoperative rotator cuff tear of less than or equal to 34 mm showed a specificity of 85.7% and a positive predictive value of 92.9% for predicting a favorable outcome. A postoperative fatty degeneration of infraspinatus muscle less than or equal to 2 had a specificity of 87.5% and a positive predictive value of 90.9% for predicting a favorable outcome.

CONCLUSIONS

Open repair of massive rotator cuff tears may reach a favorable outcome in a significant proportion of patients, despite a high rate of recurrent or residual tears. Oblique coronal sizes of the recurrent or residual tear of less than or equal to 34 mm and postoperative fatty degenerations of infraspinatus muscle of less than or equal to 2 may allow a favorable outcome.

BACKGROUND

Several studies previously reported that the postmenopausal ovary produces androgens. However, these findings have recently been questioned in a group of women with adrenal insufficiency.

OBJECTIVE

We sought to use contemporary assay methodologies to investigate whether the postmenopausal ovary is hormonally active and contributes to the circulating pool of androgens.

METHODS

Serum was collected from the ovarian veins of 13 postmenopausal women undergoing total abdominal hysterectomy and bilateral oophorectomy, with sufficient quantities obtained to allow for measurement of several hormones. Serum was also analyzed from peripheral blood collected preoperatively, intraoperatively, and postoperatively.

METHODS

The study took place at the Los Angeles County Women's and Children's Hospital, University of Southern California Keck School of Medicine.

METHODS

Testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) were measured by RIA with preceding organic solvent extraction and Celite column chromatography.

RESULTS

Statistically significant gradients were seen between the ovarian venous and peripheral samples for T, A, DHEA, E1, and E2. Postoperative levels of T and E1, but not A, DHEA, or E2, were statistically significantly lower than preoperative levels. A gradient for T between the ovarian venous and peripheral blood was present in four of five women who were menopausal for more than 10 yr.

CONCLUSIONS

The postmenopausal ovary is hormonally active, contributing significantly to the circulating pool of T. Furthermore, this contribution appears to persist in women as long as 10 yr beyond the menopause.

OBJECTIVE

To determine the rate at which clinically normal eyes in unilateral keratoconus (KC) patients progress to KC and to identify the risk factors that might predict the development of KC in a longitudinal study.

METHODS

Prospective observational study.

METHODS

We recruited 778 patients with KC and 252 normal controls in Los Angeles, California. One hundred sixteen of 778 patients (14.9%) were diagnosed with clinically unilateral KC at baseline.

METHODS

Both eyes of these unilateral KC patients were examined at baseline, and 85 patients were followed up with clinical evaluation and videokeratography for a period ranging from 6 months to 8 years.

METHODS

Progression to clinical KC from previously normal fellow eyes. Quantitative and qualitative videokeratography variables, contact lens wear, and demographic variables were analyzed as potential predictive factors for this progression.

RESULTS

During the follow-up period, 30 of 85 (35.3%) clinically normal fellow eyes had KC develop, and 25 of these 30 (83.3%) had KC develop within the first 6 years after the initial KC diagnosis. By use of the time period from the patients' first diagnosis of unilateral KC to the end of the follow-up period (range, 6 months-41 years), the median time (estimated from the survival analysis) to the development of KC was 16.7 years (95% confidence interval, 11.34, 28.91). Fellow eyes with higher inferior-superior dioptric asymmetry value (I-S) or KC percentage index (logKISA) values had higher risk for KC developing (I-S, risk ratio [RR] = 1.348, P = 0.022; log(KISA), RR = 4.245, P = 0.003). Asymmetric patterns also showed an increased risk for KC developing (P = 0.03), especially the asymmetric bowtie with skewed radial axes (AB/SRAX) pattern.

CONCLUSIONS

Approximately 50% of clinically normal fellow eyes will progress to KC within 16 years. The greatest risk is during the first 6 years of the onset. Quantitative indices (I-S and KISA values) and qualitative patterns (AB/SRAX) might predict this progression.

The CD4-8- thymocyte subset contains immature precursors for phenotypically and functionally mature CD4+8- and CD4-8+ thymocytes and peripheral T cells, as well as nonmature CD4+8+ thymocytes, most of which die in situ. The intrathymic death of most thymocytes is probably related to selective influences that ensure that only those precursors bearing self-major histocompatibility complex (MHC)-restricted and self-tolerant T-cell antigen receptors (TCR) survive to complete the maturation process. Interactions between surface molecules on thymocytes (TCR, CD4, and CD8) and thymic stromal cells (MHC proteins) are critical to repertoire selection. To understand this process, the lineage relationships among immature, nonmature, and mature thymocytes must be defined. We have examined directly the precursor-progeny relationships among CD4+8-, CD4-8+, and CD4+8+ murine thymocyte subsets by assessing their short-term (less than 5 days) developmental potentials following intrathymic injection into Thy-1 congenic, unirradiated host mice. Our results identify TCR-/lo CD4-8+ and TCRlo CD4+8+ blast cells as sequential intermediates in the development of mature TCRhi CD4+8- and TCRhi CD4-8+ thymocytes from CD4-8- precursors, thus defining at least one intrathymic maturation pathway for T lymphocytes.

Few independent studies have reported the outcome of resurfacing arthroplasty of the hip. The aim of this study was to report the five-year clinical outcome and seven-year survival of an independent series. A total of 610 Birmingham Hip Resurfacing arthroplasties were performed in 532 patients with a mean age of 51.8 years (16.5 to 81.6). They were followed for between two and eight years; 107 patients (120 hips) had been followed up for more than five years. Two patients were lost to follow-up. At a minimum of five years' follow-up, 79 of 85 hips (93%) had an excellent or good outcome according to the Harris hip score. The mean Oxford hip score was 16.1 points (sd 7.7) and the mean University of California Los Angeles activity score was 6.6 points (sd 1.9). There were no patients with definite radiological evidence of loosening or of narrowing of the femoral neck exceeding 10% of its width. There were 23 revisions (3.8%), giving an overall survival of 95% (95% confidence interval 85.3 to 99.2) at seven years. Fractured neck of femur in 12 hips was the most common indication for revision, followed by aseptic loosening in four. In three hips (three patients) (0.5%), failure was possibly related to metal debris. Considering that these patients are young and active these results are good, and support the use of resurfacing. Further study is needed to address the early failures, particularly those related to fracture and metal debris.

E-proteins are widely expressed basic helix-loop-helix (HLH) transcription factors that regulate differentiation in many cell lineages, including lymphoid, muscle, and neuronal cells. E-protein function is controlled by HLH inhibitors such as Id and SCL/TAL1 proteins, which recently have been suggested to play a role in hematopoietic stem cell (HSC) differentiation. However, the precise stages when these proteins are expressed and their specific functions are not entirely clear. Using a knock-in mouse model where the sequence for the enhanced green fluorescent protein (GFP) was inserted downstream of the Id1 promoter, we were able to track Id1 expression on an individual cell basis and detected Id1 expression in long-term repopulating HSCs (LT-HSCs). Functional assays showed that the Id1/GFP(+)Lin(-)Sca1(+)c-kit(Hi) population was highly enriched for LT-HSCs. Consistent with this expression pattern, Id1 deficiency led to a 2-fold reduction in the number of LT-HSCs defined as Lin(-)Sca1(+)c-kit(Hi)CD48(-)CD150(+). Primary bone marrow transplantation studies revealed that Id1 is dispensable for short-term engraftment. In contrast, both Id1(-/-) whole bone marrow and Lin(-)Sca1(+)c-kit(Hi)Thy1.1(Lo)-enriched HSCs, but not Id3(-/-) marrow, displayed impaired engraftment relative to wild-type controls in secondary transplantation assays. These findings suggest a unique role for Id1 in LT-HSC maintenance and hematopoietic development.

Little is known about young men who have sex with men's use of club drugs and the risk factors associated with such use. A structured survey was administered in 2005 to 496 young men who were 18-22 years old (40% were 18-19 years old); self-identified as with a same-sex sexuality (83%), bisexual (16%), and/or had had sex with a man (97%); Caucasian (35%), African American (24%), and Latino of Mexican descent (40%). Subjects were recruited from gay-identified venues in Los Angeles, California, using a venue-based probability sampling design. Descriptive statistics revealed a high prevalence of drug and club drug use. Regression analyses revealed risk factors associated with recent club drug use, including place of residence, religiosity, disclosure of sexuality to family, frequency of attendance at bars/clubs, and involvement in sexual exchange and street economy. Limitations and implications of this research are discussed.

BACKGROUND

Previous multi-institution comparisons of open and laparoscopic Roux-en-Y gastric bypass (ORYGB and LRYGB), and laparoscopic adjustable gastric banding (LAGB) have been limited by the lack of unique current procedural terminology (CPT) codes. Specific codes have been available for LRYGB and LAGB since 2005 and 2006, respectively. We compare the short-term safety of these procedures, using risk-adjusted clinical data from a multi-institutional quality improvement program.

METHODS

The America College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant Use File (PUF) was used to compare patients undergoing LRYGB with those undergoing ORYGB or LAGB.

RESULTS

ORYGB versus LRYGB: The 2-year study period (2005-2006) included 5,777 patients (ORYGB = 1,146, LRYGB = 4,631). Patients undergoing ORYGB experienced a higher 30-day incidence of mortality (0.79% vs. 0.17%; p = 0.002), major complications rate (7.42% vs. 3.37%; p < 0.0001), any complication rate (13.18% vs. 6.69%; p < 0.0001), return visits to the OR (4.97% vs. 3.56%; p = 0.032), and longer postoperative length of stay (LOS) (median 3 vs. 2 days; p < 0.0001). After risk adjustment, ORYGB continued to demonstrate higher odds of major complication (OR = 2.04; [1.54, 2.69]). LAGB versus LRYGB: Analysis of 1 year of data from 2006 included 4,756 patients (LRYGB = 3,580, LAGB = 1,176). Those treated with LAGB experienced an equivalent 30-day mortality (0.09% vs. 0.14%; p = 1.0), and a lower rate of major complications (1.0% vs. 3.3%; p < 0.0001), any complication (2.6% vs. 6.7%; p < 0.0001), return visits to the OR (0.94% vs. 3.6%; p < 0.0001), and shorter postoperative LOS (median 1 vs. 2 days; p < 0.0001). Risk adjustment showed that LAGB was associated with a lower major complication odds (OR = 0.29; [0.16, 0.53]).

CONCLUSIONS

Compared with LRYGB, ORYGB is associated with higher 30-day mortality and higher risk-adjusted major complication rate. While ORYGB may sometimes be indicated, a laparoscopic approach may be safer for RYGB when feasible. LAGB, compared with LRYGB, has a similarly low mortality rate and a small but statistically significant decrease in risk-adjusted 30-day complications. Clinical efficacy and long-term outcomes will need to be evaluated to determine superiority between these procedures.

OBJECTIVE

This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe.

METHODS

A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008.

RESULTS

Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI.

CONCLUSIONS

Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

Although it has been shown that unfractionated bone marrow, hematopoietic stem cells, common myeloid progenitors, and bipotent megakaryocyteerythrocyte progenitors can give rise to megakaryocyte colonies in culture, monopotent megakaryocyte-committed progenitors (MKP) have never been prospectively isolated from the bone marrow of adult mice. Here, we use a monoclonal antibody to the megakaryocyte-associated surface protein, CD9, to purify MKPs from the c-kit(+)Sca-1(-)IL7Ralpha(-)Thy1.1(-)Lin(-) fraction of adult C57BLKa-Thy1.1 bone marrow. The CD9(+) fraction contained a subset of CD41(+)FcgammaR(lo)CD34(+)CD38(+) cells that represent approximately 0.01% of the total nucleated bone marrow cells. They give rise mainly to colony-forming unit-megakaryocytes and occasionally burst-forming unit-megakaryocytes, with a plating efficiency >60% at the single-cell level. In vivo, MKPs do not have spleen colony-forming activity nor do they contribute to long-term multilineage hematopoiesis; they give rise only to platelets for approximately 3 weeks. Common myeloid progenitors and megakaryocyteerythrocyte progenitors can differentiate into MKPs after 72 h in stromal cultures, indicating that MKPs are downstream of these two progenitors. These isolatable MKPs will be very useful for further studies of megakaryopoiesis as well as the elucidation of their gene expression patterns.

Properdin is a positive regulator of alternative pathway (AP) complement. The current understanding of properdin function is that it facilitates AP complement activation by stabilizing the C3 convertase C3bBb. Properdin-deficient patients are susceptible to lethal meningococcal infection, but the mechanism of this selective predisposition is not fully understood. By gene targeting in the mouse, we show here that properdin is essential for AP complement activation induced by bacterial lipopolysacharride (LPS) and lipooligosacharride (LOS) and other, but not all, AP complement activators. LPS- and LOS-induced AP complement activation was abolished in properdin-/- mouse serum, and properdin-/- mice were unable to clear Crry-deficient erythrocytes, which are known to be susceptible to AP complement-mediated extravascular hemolysis. In contrast, zymosan- and cobra venom factor-induced AP complement activation, and classical pathway-triggered AP complement amplification were only partially or minimally affected in properdin-/- mice. We further show that the ability of human properdin to restore LPS-dependent AP complement activity in properdin-/- mouse serum correlated with the human properdin-binding affinity of the LPS. These results reveal a novel role of properdin in AP complement initiation and have implications for understanding the selective predisposition of properdin-deficient patients to meningococcal infection.

OBJECTIVE

To examine how depressive symptoms, a history of depression, and cognitive functioning contribute to the prediction of rehabilitation efficiency in stroke patients.

METHODS

Consecutive admissions to an acute inpatient rehabilitation program were screened for cognitive functioning and level of depressive symptoms. History of depression was determined by family member interview. Functional status was evaluated at time of admission and discharge. Depressive symptoms, depression history, and cognitive functioning were examined as predictors of length of stay (LOS) and efficiency of utilization of rehabilitation services.

METHODS

Acute inpatient rehabilitation hospital.

METHODS

A total of 348 consecutive stroke admissions to an inpatient program were evaluated for depression and cognitive functioning, of whom 243 patients completed all aspects of the screening.

METHODS

Not applicable.

METHODS

Rehabilitation progress, measured with the LOS efficiency measure (LOS-EFF) of the FIM instrument, and length of rehabilitation hospital stay.

RESULTS

Patients with higher levels of depressive symptoms used rehabilitation services less efficiently than those with lower symptom levels but did not have longer LOSs. History of depression was associated with longer LOS and less efficient use of rehabilitation services. Cognitive impairment did not predict rehabilitation efficiency.

CONCLUSIONS

The present study lends further support to the benefits of screening stroke patients at the time of rehabilitation admission for depression and history of depression. Identifying patients who have high levels of depressive symptoms and/or a previous depressive episode will allow more comprehensive assessment and rapid intervention.

DNA-protein cross-links (DPCs) are formed upon exposure to a variety of chemical and physical agents and pose a threat to genomic integrity. In particular, acrolein and related aldehydes produce DPCs, although the chemical linkages for such cross-links have not been identified. Here, we report that oligodeoxynucleotides containing 1,N(2)-deoxyguanosine adducts of acrolein, crotonaldehyde, and trans-4-hydroxynonenal can form cross-links with the tetrapeptide Lys-Trp-Lys-Lys. We concluded that complex formation is mediated by a Schiff base linkage because DNA-peptide complexes were covalently trapped following reduction with sodium cyanoborohydride, and pre-reduction of adducted DNAs inhibited complex formation. A previous NMR study demonstrated that duplex DNA catalyzes ring opening for the acrolein-derived gamma-hydroxy-1,N(2)-propanodeoxyguanosine adduct to yield an aldehydic function (de los Santos, C., Zaliznyak, T., and Johnson, F. (2001) J. Biol. Chem. 276, 9077-9082). Consistent with this earlier observation, the adducts under investigation were more reactive in duplex DNA than in single-stranded DNA, and we concluded that the ring-open aldehydic moiety is the induced tautomer in duplex DNA for adducts exhibiting high relative reactivity. Adducted DNA cross-linked to Arg-Trp-Arg-Arg and Lys-Trp-Lys-Lys with comparable efficiency, and N(alpha)-acetylation of peptides dramatically inhibited trapping; thus, the reactive nucleophile is located at the N-terminal alpha-amine of the peptide. These data suggest that Schiff base chemistry can mediate DPC formation in vivo following the formation of stable aldehyde-derived DNA adducts.

BACKGROUND

Hospital cost containment, cost reduction, and alternative care delivery systems continue to preoccupy health care providers, payers, employers, and policy makers throughout the United States. The universal metric for gauging the success of these efforts is hospital length of stay (LOS). Reducing the LOS purportedly yields large cost savings. The purpose of this study is to assess precisely how much hospitals save by shortening LOS.

METHODS

We reviewed the cost-accounting records of all surviving patients (n = 12,365) discharged from our academic medical center during fiscal year 1998 with LOS of 4 days or more. Actual costs were identified through the University of Michigan cost-accounting system. Individual patient costs were broken out on a daily basis and then decomposed further into variable direct, fixed direct, and indirect categories. The population was analyzed by determining the incremental resource cost of the last full day of stay versus the total cost for the entire stay. The data were also stratified by LOS and by surgical costs. An analysis of all trauma patients was then performed on all patients discharged from the hospital's adult level I trauma center (n = 665). Costs were determined on specific days, including admission day, each ICU day, day of discharge from the ICU, and each of the last 2 days before the discharge day.

RESULTS

The incremental costs incurred by patients on their last full day of hospital stay were $420 per day on average, or just 2.4% of the $17,734 mean total cost of stay for all 12,365 patients. Mean end-of-stay costs represented only a slightly higher percentage of total costs when LOS was short (e.g., 6.8% for patients with LOS of 4 days). Even when the data were stratified to focus on patients without major operations, the $432 average last-day variable direct cost was only 3.4% of the $12,631 average total cost of care. A focus on the trauma center helps to explain this phenomenon. For our trauma center, variable direct costs accounted for 42% of the mean total cost per patient of $22,067. The remaining 58% was hospital overhead (fixed and indirect costs). The median variable direct cost on the first day of admission is $1,246, and the median variable direct cost on discharge is $304. Approximately 40% of the variable costs are incurred during the first 3 days of admission.

CONCLUSIONS

For most patients, the costs directly attributable to the last day of a hospital stay are an economically insignificant component of total costs. Reducing LOS by as much as 1 full day reduces the total cost of care on average by 3% or less. Going forward, physicians and administrators must deemphasize LOS and focus instead on process changes that better use capacity and alter care delivery during the early stages of admission, when resource consumption is most intense.

BACKGROUND

Health care disparities have been identified in the treatment of older and racial/ethnic minority breast carcinoma patients. The purpose of the current study was to examine racial/ethnic group differences in the treatment decision-making process of older breast carcinoma patients and the differential impact on treatment received.

METHODS

A cross-sectional survey was conducted of a population-based, consecutive sample identified by the Los Angeles Cancer Surveillance Program comprised of Latina (n = 99), African-American (n = 66), and white (n = 92) women age>> or = 55 years (total n = 257) and who were between 3-9 months after their primary breast carcinoma diagnosis.

RESULTS

Approximately 49% of less acculturated Latinas and 18% of more acculturated Latinas indicated that their family members determined the final treatment decision, compared with less than 4% of African-Americans and whites (P < 0.001). This disparity remained in multiple logistic regression analysis, controlling for potential confounders, including sociodemographic, physician-patient communication, social support, and health variables. Compared with African-American and white women, Latina women were more likely to identify a family member as the final treatment decision-maker (adjusted odds ratio [AOR] of 7.97; 95% confidence interval [95% CI], 2.43-26.20, for less acculturated Latinas; and AOR of 4.48; 95% CI, 1.09-18.45, for more acculturated Latinas). A multiple logistic regression model, controlling for sociodemographic and health characteristics, indicated that patients were less likely to receive breast-conserving surgery (BCS) when the family made the final treatment decision (AOR of 0.39; 95% CI, 0.18-0.85).

CONCLUSIONS

Family appears to play a powerful role in treatment decision-making among older Latina breast carcinoma patients, regardless of the level of acculturation. This family influence appears to contribute to racial/ethnic group differences in treatment received. Physicians should acknowledge and educate patients' family members as potential key participants in medical decision-making, rather than merely as translators and providers of social support.

Lo-MYC and Hi-MYC mice develop prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma as a result of MYC overexpression in the mouse prostate. However, prior studies have not determined precisely when, and in which cell types, MYC is induced. Using immunohistochemistry (IHC) to localize MYC expression in Lo-MYC transgenic mice, we show that morphological and molecular alterations characteristic of high grade PIN arise in luminal epithelial cells as soon as MYC overexpression is detected. These changes include increased nuclear and nucleolar size and large scale chromatin remodeling. Mouse PIN cells retained a columnar architecture and abundant cytoplasm and appeared as either a single layer of neoplastic cells or as pseudo-stratified/multilayered structures with open glandular lumina-features highly analogous to human high grade PIN. Also using IHC, we show that the onset of MYC overexpression and PIN development coincided precisely with decreased expression of the homeodomain transcription factor and tumor suppressor, Nkx3.1. Virtually all normal appearing prostate luminal cells expressed high levels of Nkx3.1, but all cells expressing MYC in PIN lesions showed marked reductions in Nkx3.1, implicating MYC as a key factor that represses Nkx3.1 in PIN lesions. To determine the effects of less pronounced overexpression of MYC we generated a new line of mice expressing MYC in the prostate under the transcriptional control of the mouse Nkx3.1 control region. These "Super-Lo-MYC" mice also developed PIN, albeit a less aggressive form. We also identified a histologically defined intermediate step in the progression of mouse PIN into invasive adenocarcinoma. These lesions are characterized by a loss of cell polarity, multi-layering, and cribriform formation, and by a "paradoxical" increase in Nkx3.1 protein. Similar histopathological changes occurred in Hi-MYC mice, albeit with accelerated kinetics. Our results using IHC provide novel insights that support the contention that MYC overexpression is sufficient to transform prostate luminal epithelial cells into PIN cells in vivo. We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas.

Clonal deletion of autoreactive thymocytes is important for self-tolerance, but the intrathymic signals that induce clonal deletion have not been clearly identified. We now report that clonal deletion during negative selection required CD28-mediated costimulation of autoreactive thymocytes at the CD4(+)CD8(lo) intermediate stage of differentiation. Autoreactive thymocytes were prevented from undergoing clonal deletion by either a lack of CD28 costimulation or transgenic overexpression of the antiapoptotic factors Bcl-2 or Mcl-1, with surviving thymocytes differentiating into anergic CD4(-)CD8(-) double-negative thymocytes positive for the T cell antigen receptor αβ subtype (TCRαβ) that 'preferentially' migrated to the intestine, where they re-expressed CD8α and were sequestered as CD8αα(+) intraepithelial lymphocytes (IELs). Our study identifies costimulation by CD28 as the intrathymic signal required for clonal deletion and identifies CD8αα(+) IELs as the developmental fate of autoreactive thymocytes that survive negative selection.

The relation between exposure to electric and magnetic fields in the home, as assessed by measurements, wiring configuration, and self-reported appliance use, and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California. Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random digit dialing. Interviews were obtained from 232 cases and 232 controls. Available for analysis were measurements of the magnetic field in the child's bedroom over 24 hours or longer (164 cases and 144 controls), spot measurements of magnetic and electric fields (140 cases and 109 controls), and wiring configuration (219 cases and 207 controls). No clear associations between leukemia risk and measured magnetic or electric fields were seen. An association between the Denver Wertheimer-Leeper wiring configuration and childhood leukemia risk was observed (odds ratio for very high relative to very low current and underground configuration combined = 2.15, 95% confidence interval 1.08-4.28; p for trend = 0.008) and was not substantially altered by adjustment for potential confounding factors. Cases were more likely than controls to report use of several appliances that produce high electric and magnetic fields. Our results support an association between childhood leukemia risk and wiring configuration, but not direct measurements of electric and magnetic fields.

OBJECTIVE

Person-centred care (PCC) emphasizes a partnership in care between patients and healthcare professionals and is advocated by WHO as a key component of quality health care. We evaluated outcomes of PCC in hospitalized patients with chronic heart failure (CHF) with respect to the length of hospital stay (LOS), activities of daily living (ADL), health-related quality of life (HRQL) and 6-month readmission rate.

RESULTS

During 2008-2010, 248 consecutive patients hospitalized for symptoms of worsening CHF were enrolled in a controlled before and after designed study. A Usual care group (n= 123) was recruited according to pre-defined criteria to map usual CHF care and assess outcomes at five designated hospital wards. Based on the mapping, a panel of in-house clinicians and researchers developed measures aimed at aligning usual care with basic PCC principles. These measures were incorporated into a study protocol to guide care procedures at the same five wards. Person-centred care was then implemented at these wards and evaluated in 125 patients. Both length of hospital stay and 6-month readmission were extracted from patient records. Activities of daily living were evaluated at baseline and discharge and HRQL was evaluated at baseline and after 3 months. In the analysis of all patients, the LOS was reduced by 1 day (P = 0.16) while retaining ADL (P = 0.07). When PCC was fully implemented (per protocol analysis), LOS was reduced by 2.5 days (P = 0.01) and the ADL-level better preserved (P = 0.04). Health-related quality of life and time-to-first readmission did not differ.

CONCLUSIONS

In this proof-of-concept study, our findings suggest that a fully implemented PCC approach shortens hospital stay and maintains functional performance in patients hospitalized for worsening CHF, without increasing risk for readmission or jeopardizing patients' HRQL.

BACKGROUND

In-hospital mortality measures, which are widely used to assess hospital quality, are not based on a standardized follow-up period and may systematically favor hospitals with shorter lengths of stay (LOSs).

OBJECTIVE

To assess the agreement between performance measures of U.S. hospitals by using risk-standardized in-hospital and 30-day mortality rates.

METHODS

Observational study.

METHODS

Nonfederal acute care hospitals in the United States with at least 30 admissions for acute myocardial infarction (AMI), heart failure (HF), and pneumonia from 2004 to 2006.

METHODS

Medicare fee-for-service patients admitted for AMI, HF, or pneumonia from 2004 to 2006.

METHODS

The primary outcomes were in-hospital and 30-day risk-standardized mortality rates (RSMRs).

RESULTS

Included patients comprised 718,508 admissions to 3135 hospitals for AMI, 1,315,845 admissions to 4209 hospitals for HF, and 1,415,237 admissions to 4498 hospitals for pneumonia. The hospital-level mean patient LOS varied across hospitals for each condition, ranging from 2.3 to 13.7 days for AMI, 3.5 to 11.9 days for HF, and 3.8 to 14.8 days for pneumonia. The mean RSMR differences (30-day RSMR minus in-hospital RSMR) were 5.3% (SD, 1.3) for AMI, 6.0% (SD, 1.3) for HF, and 5.7% (SD, 1.4) for pneumonia; distributions varied widely across hospitals. Performance classifications differed between the in-hospital and 30-day models for 257 hospitals (8.2%) for AMI, 456 (10.8%) for HF, and 662 (14.7%) for pneumonia. Hospital mean LOS was positively correlated with in-hospital RSMRs for all 3 conditions.

CONCLUSIONS

Medicare claims data were used for risk adjustment.

CONCLUSIONS

In-hospital mortality measures provide a different assessment of hospital performance than 30-day mortality and are biased in favor of hospitals with shorter LOSs.

BACKGROUND

The Centers for Medicare & Medicaid Services and National Heart, Lung, and Blood Institute.

OBJECTIVE

To assess the association between protease inhibitor (PI) use and the incidence of diabetes mellitus (DM) among participants in the Women's Interagency HIV Study.

METHODS

Prospective multicenter cohort study. The diagnosis of DM was based on self-report at semiannual interviews conducted from 1994 to 1998.

METHODS

Six inner-city clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA).

METHODS

A total of 1785 nonpregnant women who had no history of prior DM. The women made up four groups: 1) PI users (n = 609, person-years [PY] at risk = 707); 2) reverse transcriptase inhibitor (RTI)-only users (n = 932, PY = 1486); 3) HIV-infected women reporting no antiretroviral therapy (ART) ever (n = 816, PY = 1480); and 4) HIV-uninfected women (n = 350, PY = 905).

RESULTS

Incidence of DM and median body mass index (BMI) from 1995 to 1998 were compared among the four groups.

RESULTS

Sixty-nine incident cases of DM occurred among 1785 women (1.5 cases per 100 PY; 95% CI: 1.2-1.9). The incidence of DM among PI users was 2.8 cases per 100 PY (2.8%) versus 1.2% among both RTI users and women on no ART (95% CI: 1.6-4.1 [PI]; 0.7-1.8 [RTI and no ART]; P = 0.01 for comparison of the PI group with the RTI group) and 1.4% among HIV-uninfected women (95% CI: 0.7-2.2, P = 0.06 for comparison with PI group). Weight gain was not associated with either PI or RTI use. Multivariate models identified PI use (hazard ratio [HR] = 2.90 [95% CI: 1.50-5.60]; P = 0.002), age (HR = 1.75 per 10 years [95% CI: 1.31-2.34]; P = 0.0002) and BMI as independent risk factors for DM.

CONCLUSIONS

PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.