Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesterol-dependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chain-containing phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.

Two important databases are often used in HIV genetic research, the HIV Sequence Database in Los Alamos, which collects all sequences and focuses on annotation and data analysis, and the HIV RT/Protease Sequence Database in Stanford, which collects sequences associated with the development of viral resistance against anti-retroviral drugs and focuses on analysis of those sequences. The types of data and services these two databases offer, the tools they provide, and the way they are set up and operated are described in detail.

Several important events occur at the maternal-fetal interface, including generation of maternal-fetal tolerance, remodeling of the uterine smooth muscle and its spiral arteries and glands, and placental construction. Fetal-derived extravillous trophoblasts come in direct contact with maternal decidual leukocytes. Macrophages represent ∼20% of the leukocytes at this interface. In this study, two distinct subsets of CD14(+) decidual macrophages (dMs) are found to be present in first-trimester decidual tissue, CD11c(HI) and CD11c(LO). Gene expression analysis by RNA microarray revealed that 379 probes were differentially expressed between these two populations. Analysis of the two subsets revealed several clusters of coregulated genes that suggest distinct functions for these subsets in tissue remodeling, growth, and development. CD11c(HI) dMs express genes associated with lipid metabolism and inflammation, whereas CD11c(LO) dMs express genes associated with extracellular matrix formation, muscle regulation, and tissue growth. The CD11c(HI) dMs also differ from CD11c(LO) dMs in their ability to process protein Ag and are likely to be the major APCs in the decidua. Moreover, these populations each secrete both proinflammatory and anti-inflammatory cytokines that may contribute to the balance that establishes fetal-maternal tolerance. Thus, they do not fit the conventional M1/M2 categorization.

OBJECTIVE

This study examined the association between acculturation of Mexican-origin women and factors in low birthweight and preterm delivery.

METHODS

Interviews were conducted with 911 Mexican-origin respondents in Los Angeles prenatal care clinics. Infant outcome data were retrieved from delivery records.

RESULTS

Mexican-American women had generally more undesirable prenatal behaviors and risk factors than Mexican-immigrant women. Although higher acculturation was significantly associated with behavioral risk factors, there were no direct effects of acculturation on infant gestational age or birthweight.

CONCLUSIONS

Future research needs to measure multiple factors to assess their effects on culture-specific protective factors.

OBJECTIVE

To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer.

METHODS

A retrospective cohort study using administrative data.

METHODS

We analyzed the medical bills for the 6,308 Medicare patients>> 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993. The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes. Patient sociodemographic and disease characteristics were obtained from the SEER database and census data.

RESULTS

Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy.

CONCLUSIONS

Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing. However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions.

Phase diagrams of ternary lipid mixtures containing cholesterol have provided valuable insight into cell membrane behaviors, especially by describing regions of coexisting liquid-disordered (Ld) and liquid-ordered (Lo) phases. Fluorescence microscopy imaging of giant unilamellar vesicles has greatly assisted the determination of phase behavior in these systems. However, the requirement for optically resolved Ld + Lo domains can lead to the incorrect inference that in lipid-only mixtures, Ld + Lo domain coexistence generally shows macroscopic domains. Here we show this inference is incorrect for the low melting temperature phosphatidylcholines abundant in mammalian plasma membranes. By use of high compositional resolution Förster resonance energy transfer measurements, together with electron spin resonance data and spectral simulation, we find that ternary mixtures of DSPC and cholesterol together with either POPC or SOPC, do indeed have regions of Ld + Lo coexistence. However, phase domains are much smaller than the optical resolution limit, likely on the order of the Förster distance for energy transfer (R(0), ∼2-8 nm).

BACKGROUND

There is growing evidence that, when smoking habits are comparable, women incur a higher risk of lung cancer than men. Because smokers are also at risk for bladder cancer, we investigated possible sex differences in the susceptibility to bladder cancer among smokers.

METHODS

A population-based, case--control study was conducted in Los Angeles, CA, involving 1514 case patients with bladder cancer and 1514 individually matched population control subjects. Information on tobacco use was collected through in-person interviews. Peripheral blood was collected from study participants to measure 3- and 4-aminobiphenyl (ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to determine whether the risk of bladder cancer differs between male and female smokers and whether female smokers exhibit higher levels of ABP-hemoglobin adducts than male smokers with comparable smoking habits. All statistical tests were two-sided.

RESULTS

Cigarette smokers had a statistically significant 2.5-fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus higher tar cigarettes, or the pattern of inhalation did not modify the risk. The risk of bladder cancer in women who smoked was statistically significantly higher than that in men who smoked comparable numbers of cigarettes (P =.016 for sex-lifetime smoking interaction). Consistent with the sex difference in smoking-related bladder cancer risk, the slopes of the linear regression lines of the 3- and 4-ABP--hemoglobin adducts by cigarettes per day were statistically significantly steeper in women than in men (P values for sex differences <.001 and.006, respectively).

CONCLUSIONS

The risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes.

Quality of life issues must be addressed more vigorously in the care of chronic mental patients. In a survey of 30 large board-and-care homes in Los Angeles, 278 mentally disabled residents described their life conditions and satisfaction in eight areas: living situation, family relations, social relations, leisure activities, work, finances, safety, and health. Residents were less satisfied than the general population in most life areas, especially finances, unemployment, safety, and family and social relations (p less than .001). Of particular concern was the finding that 34% had been recent victims of crime. The results underscore the need for better social programs for these patients.

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.

BACKGROUND

Recent studies suggest that many tuberculosis cases in urban areas result from recent transmission. Delineation of the epidemiologic links between patients is important to optimize strategies to reduce tuberculosis transmission.

OBJECTIVE

To identify epidemiologic links among recently infected urban patients with tuberculosis.

METHODS

Prospective evaluation of patients with tuberculosis.

METHODS

Central Los Angeles, Calif.

METHODS

A total of 162 patients who had culture-proven tuberculosis.

METHODS

Patients were prospectively interviewed to identify their contacts and whereabouts. The IS6110-based and pTBN12-based restriction fragment length polymorphism analyses were performed on Mycobacterium tuberculosis isolates. Patients whose isolates had identical or closely related restriction fragment length polymorphism patterns were considered a cluster. Unconditional logistic regression was used to identify independent predictors of clustering.

METHODS

Relationship of clinical and epidemiologic variables to clustering.

RESULTS

A total of 96 (59%) of 162 patients were in 8 clusters. Only 2 of the 96 clustered patients named others in the cluster as contacts. The degree of homelessness was an independent predictor of clustering. Compared with nonclustered patients, patients in 6 clusters were significantly more likely to have spent time at 3 shelters and other locations when at least 1 patient in the cluster was contagious, and these locations were independent predictors of clustering. Among nonhomeless persons, clustered patients were significantly more likely than nonclustered patients to have used daytime services at 3 shelters.

CONCLUSIONS

(1) Traditional contact investigation does not reliably identify patients infected with the same M tuberculosis strain, and (2) locations at which the homeless congregate are important sites of tuberculosis transmission for homeless and nonhomeless persons. Measures that reduce tuberculosis transmission should be based on locations rather than on personal contacts.

OBJECTIVE

Intake of fruits and vegetables protects against several common chronic diseases, and low income is associated with lower intake. We tested the effectiveness of a subsidy for fruits and vegetables to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

METHODS

Women who enrolled for postpartum services (n=602) at 3 WIC sites in Los Angeles were assigned to an intervention (farmers' market or supermarket, both with redeemable food vouchers) or control condition (a minimal nonfood incentive). Interventions were carried out for 6 months, and participants' diets were followed for an additional 6 months.

RESULTS

Intervention participants increased their consumption of fruits and vegetables and sustained the increase 6 months after the intervention was terminated (model adjusted R(2)=.13, P<.001). Farmers' market participants showed an increase of 1.4 servings per 4186 kJ (1000 kcal) of consumed food (P<.001) from baseline to the end of intervention compared with controls, and supermarket participants showed an increase of 0.8 servings per 4186 kJ (P=.02).

CONCLUSIONS

Participants valued fresh fruits and vegetables, and adding them to the WIC food packages will result in increased fruit and vegetable consumption.

BACKGROUND

Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children.

METHODS

Records at the Childrens Hospital Los Angeles were reviewed for children with>> or =1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained.

RESULTS

A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8-20.5 years). A 2-compartment Michaelis-Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration <1000 ng/mL was associated with a 2.6-fold increased odds of death (95% confidence interval, 1.6-4.8; P=.002). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or an oral dose of 200 mg twice daily would achieve a trough >1000 ng/mL in most patients, but with a wide range of possible concentrations.

CONCLUSIONS

We found a pharmacodynamic association between a voriconazole trough >1000 ng/mL and survival and marked pharmacokinetic variability, particularly after enteral dosing, justifying the measurement of serum concentrations.

BACKGROUND

Postoperative ileus, a transient impairment of gastrointestinal motility, is a common cause of delay in return to normal bowel function after abdominal surgery. Colectomy surgery patients who develop postoperative ileus could have greater health care resource utilization, including prolonged hospitalization, compared with those who do not develop postoperative ileus. Very few studies have assessed the impact of postoperative ileus on resource utilization and costs using retrospective analysis of administrative databases.

OBJECTIVE

To assess health care utilization and costs in colectomy surgery patients who developed postoperative ileus versus those who did not.

METHODS

A retrospective cohort study design was used. Adult patients with a principal procedure code for colectomy (ICD-9-CM procedure codes 45.71-45.79), discharged between January 1, 2004, and December 31, 2004, were identified from the Premier Perspective database of inpatient records from more than 500 hospitals in the United States. The colectomy patients were further classified for the presence of postoperative ileus, identified by the presence, in any diagnosis field on the administrative patient records, of a code for paralytic ileus (ICD-9-CM code 560.1) and/or digestive system complications (ICD-9-CM code 997.4) during the inpatient stay. Code 997.4 was used to account for cases in which postoperative ileus would be reported as a complication of anastomosis, as could be the case in colectomy surgeries. Hospital length of stay (LOS) and hospitalization costs were compared using t-tests. Multivariate analyses were performed with log-transformed LOS and log-transformed cost as the dependent variables. Patient demographics, mortality risk, disease severity, admission source, payment type (retrospective/prospective), and hospital characteristics were used as covariates.

RESULTS

A total of 17,876 patients with primary procedure code for colectomy were identified, of whom 3115 (17.4%) patients were classified for presence of postoperative ileus (including paralytic ileus only [n=1216; 6.8%], digestive system complications only [n=383; 2.1%], or both [n=1516; 8.5%]). A majority of the colectomy patients with and without postoperative ileus, respectively, were male (54.1% vs. 50.3%, P < 0.001), Caucasian (70.5% vs. 69.3%, P = 0.170), and aged 51-64 years (51.1% vs. 49.7%, P = 0.143). The mean [SD] hospital LOS was significantly longer in patients with postoperative ileus (13.8 [13.3] days) compared with patients without postoperative ileus (8.9 [9.5] days; P < 0.001). Presence of postoperative ileus was found to be a significant predictor of LOS (P < 0.001) in the regression model, controlling for covariates. Female gender (P = 0.002), greater severity level (P < 0.001), and hospital bed size of more than 500 (P = 0.013) were other significant predictors of hospital LOS. Presence of postoperative ileus was found to be a significant predictor of hospitalization costs (P < 0.001), controlling for covariates.

CONCLUSIONS

Postoperative ileus in colectomy patients is a significant predictor of hospital resource utilization.

CONCLUSIONS

HIV risky behaviors and health practices were examined among young people living with HIV (YPLH) in Los Angeles, San Francisco, and New York over 15 months in response to receiving a preventive intervention. YPLH aged 16 to 29 years (n = 175; 26% black and 42% Latino; 69% gay men) were randomly assigned to a 3-module intervention totaling 18 sessions delivered by telephone, in person, or a delayed-intervention condition. Intention-to-treat analyses found that the in-person intervention resulted in a significantly higher proportion of sexual acts protected by condoms overall and with HIV-seronegative partners. Pre- and postanalyses of YPLH in the delayed-intervention condition alone found that YPLH tended to have fewer sexual partners, used fewer drugs, reported less emotional distress, and decreased their use of antiretroviral therapies. Prevention programs can be delivered in alternative formats while retaining efficacy. When YPLH are using hard drugs, drug treatment may be needed before delivery of preventive interventions.

Nontypeable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract infections, including otitis media and bronchitis. The persistence of NTHi in vivo is thought to involve bacterial persistence in a biofilm community. Therefore, there is a need for further definition of bacterial factors contributing to biofilm formation by NTHi. Like other bacteria inhabiting host mucosal surfaces, NTHi has on its surface a diverse array of lipooligosaccharides (LOS) that influence host-bacterial interactions. In this study, we show that LOS containing sialic (N-acetyl-neuraminic) acid promotes biofilm formation by NTHi in vitro and bacterial persistence within the middle ear or lung in vivo. LOS from NTHi in biofilms was sialylated, as determined by comparison of electrophoretic mobilities and immunochemical reactivities before and after neuraminidase treatment. Biofilm formation was significantly reduced in media lacking sialic acid, and a siaB (CMP-sialic acid synthetase) mutant was deficient in biofilm formation in three different in vitro model systems. The persistence of an asialylated siaB mutant was attenuated in a gerbil middle ear infection model system, as well as in a rat pulmonary challenge model system. These data show that sialylated LOS glycoforms promote biofilm formation by NTHi and persistence in vivo.

BACKGROUND

Reducing length of stay (LOS) has been a priority for hospitals and health care systems. However, there is concern that this reduction may result in increased hospital readmissions.

OBJECTIVE

To determine trends in hospital LOS and 30-day readmission rates for all medical diagnoses combined and 5 specific common diagnoses in the Veterans Health Administration.

METHODS

Observational study from 1997 to 2010.

METHODS

All 129 acute care Veterans Affairs hospitals in the United States.

METHODS

4,124,907 medical admissions with subsamples of 2 chronic diagnoses (heart failure and chronic obstructive pulmonary disease) and 3 acute diagnoses (acute myocardial infarction, community-acquired pneumonia, and gastrointestinal hemorrhage).

METHODS

Unadjusted LOS and 30-day readmission rates with multivariable regression analyses to adjust for patient demographic characteristics, comorbid conditions, and admitting hospitals.

RESULTS

For all medical diagnoses combined, risk-adjusted mean hospital LOS decreased by 1.46 days from 5.44 to 3.98 days, or 2% annually (P < 0.001). Reductions in LOS were also observed for the 5 specific common diagnoses, with greatest reductions for acute myocardial infarction (2.85 days) and community-acquired pneumonia (2.22 days). Over the 14 years, risk-adjusted 30-day readmission rates for all medical diagnoses combined decreased from 16.5% to 13.8% (P < 0.001). Reductions in readmissions were also observed for the 5 specific common diagnoses, with greatest reductions for acute myocardial infarction (22.6% to 19.8%) and chronic obstructive pulmonary disease (17.9% to 14.6%). All-cause mortality 90 days after admission was reduced by 3% annually. Of note, hospitals with mean risk-adjusted LOS that was lower than expected had a higher readmission rate, suggesting a modest tradeoff between hospital LOS and readmission (6% increase for each day lower than expected).

CONCLUSIONS

This study is limited to the Veterans Health Administration system; non-Veterans Affairs admissions were not available. No measure of readmission preventability was used.

CONCLUSIONS

Veterans Affairs hospitals demonstrated simultaneous improvements in hospital LOS and readmissions over 14 years, suggesting that as LOS improved, hospital readmission did not increase. This is important because hospital readmission is being used as a quality indicator and may result in payment incentives. Future work should explore these relationships to see whether a tipping point exists for LOS reduction and hospital readmission.

BACKGROUND

Office of Rural Health and the Health Services Research & Development Service, Veterans Health Administration, U.S. Department of Veterans Affairs.

OBJECTIVE

The authors have developed a novel technique for percutaneous fusion in which standard microendoscopic discectomy is modified. Based on data obtained in their cadaveric studies they considered that this minimally invasive interbody fusion could be safely implemented clinically. The authors describe their initial experience with a microendoscopic transforaminal lumbar interbody fusion (METLIF) technique, with regard to safety in the placement of percutaneous instrumentation, perioperative morbidity, and early postoperative results.

METHODS

The METLIF procedure was performed unilaterally in 20 patients with single-level lumbar spondylolisthesis or pure mechanical back pain with endoscopic assistance, hemilaminectomy, unilateral facetectomy, and microdiscectomy. Two interbody grafts were placed via the lateral exposure of the disc space. Bilateral percutaneous pedicle screws were then inserted. Compared with patients who had undergone single-level posterior LIF at the same institutions, intraoperative blood loss, hospital length of stay (LOS), and postoperative narcotic agent use were significantly lower in the METLIF group. The mean LOS for the percutaneous fusion group was 3.4 days (5.1 days in those who underwent PLIF; p < 0.02). There have been no procedure-related complications in this series to date.

CONCLUSIONS

The METLIF technique provided an option for percutaneous interbody fusion similar to that in open surgery while minimizing destruction to adjacent tissues. This technique was safe and exhibited a trend toward decreased intraoperative blood loss, postoperative pain, total narcotic use, and the risk of transfusion.

OBJECTIVE

Evaluation and validation of the psychometric properties of the eight-item modified Medical Outcomes Study Social Support Survey (mMOS-SS).

METHODS

Secondary analyses of data from three populations: Boston breast cancer study (N=660), Los Angeles breast cancer study (N=864), and Medical Outcomes Study (N=1,717). The psychometric evaluation of the eight-item mMOS-SS compared performance across populations and with the original 19-item Medical Outcomes Study Social Support Survey (MOS-SS). Internal reliability, factor structure, construct validity, and discriminant validity were evaluated using Cronbach's alpha, principal factor analysis (PFA), and confirmatory factor analysis (CFA), Spearman and Pearson correlation, t-test and Wilcoxon rank sum tests.

RESULTS

mMOS-SS internal reliability was excellent in all three populations. PFA factor loadings were similar across populations; one factor >0.6, well-discriminated two factor (instrumental/emotional social support four items each) >0.5. CFA with a priori two-factor structure yielded consistently adequate model fit (root mean squared errors of approximation 0.054-0.074). mMOS-SS construct and discriminant validity were similar across populations and comparable to MOS-SS. Psychometric properties held when restricted to women aged ≥ 65 years.

CONCLUSIONS

The psychometric properties of the eight-item mMOS-SS were excellent and similar to those of the original 19-item instrument. Results support the use of briefer mMOS-SS instrument; better suited to multidimensional geriatric assessments and specifically in older women with breast cancer.

BACKGROUND

Studies comparing the costs of colorectal resection by laparoscopic (LPS) and open approaches are small sized or not randomized. The main purpose of this study is to compare the hospital costs of LPS and open colorectal surgery in a large series of randomized patients.

METHODS

A total of 517 patients with colorectal disease were randomly assigned to LPS (n = 258) or open (n = 259) resection. The following costs were calculated: surgical instruments, operative room (OR) occupation, routine care, postoperative morbidity, and length of hospital stay (LOS). Follow-up for postoperative morbidity was carried out for 30 days after hospital discharge.

RESULTS

Operative time was 37 minutes longer in the LPS group. Overall morbidity rate was 18.2% (47 of 258) in the LPS versus 34.7% (90 of 259) in the open group (P = 0.0005). The mean LOS was 9.9 (2.6) days in the LPS group and 12.4 (3.9) days in the open group (P < 0.0001). The additional OR charge in the LPS group was 1171 per patient randomized (864 due to surgical instruments and 307 due to longer time). The saving in the LPS group was 1046 per patient randomized (401 due to shorter LOS and 645 due to the lower cost of postoperative complications). The net balance resulted in 125 extra cost per patient allocated to the LPS group.

CONCLUSIONS

The present cost-benefit analysis showed a slight additional cost in the LPS group. The better postoperative short-term outcome in patients receiving LPS had a key role to nearly balance the operative room charges due to laparoscopy.

The purpose of this study was to identify factors that may facilitate or impede future adoption of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men in HIV-serodiscordant relationships. This qualitative study utilized semistructured interviews conducted with a multiracial/-ethnic sample of 25 gay and bisexual HIV-serodiscordant male couples (n=50 individuals) recruited from community settings in Los Angeles, CA. A modified grounded theory approach was employed to identify major themes relating to future adoption of PrEP for HIV prevention. Motivators for adoption included protection against HIV infection, less concern and fear regarding HIV transmission, the opportunity to engage in unprotected sex, and endorsements of PrEP's effectiveness. Concerns and barriers to adoption included the cost of PrEP, short- and long-term side effects, adverse effects of intermittent use or discontinuing PrEP, and accessibility of PrEP. The findings suggest the need for a carefully planned implementation program along with educational and counseling interventions in the dissemination of an effective PrEP agent.

International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. Consistency in numbering is also increasingly required for functional and clinical studies of HCV. For example, an unambiguous method for referring to amino acid substitutions at specific positions in NS3 and NS5B coding sequences associated with resistance to specific HCV inhibitors is essential in the investigation of antiviral treatment. Inconsistent and inaccurate numbering of locations in DNA and protein sequences is becoming a problem in the HCV scientific literature.A group of experts in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and the Los Alamos National Laboratory (United States), convened to reexamine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. They also discussed how HCV sequence databases could introduce and facilitate a standardized numbering system for HCV nucleotides, proteins, and epitopes.A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. A consensus proposal was drawn up for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. The proposed numbering system was adapted from the Los Alamos HIV database, with elements from the hepatitis B virus numbering system. The system comprises both nucleotides and amino acid sequences and epitopes, and uses the full-length genome sequence of isolate H77 (accession number AF009606) as a reference. It includes a method for numbering insertions and deletions relative to this reference sequence.

The generation of sensory and autonomic neurons from the neural crest requires the functions of two classes of basic helix-loop-helix (bHLH) transcription factors, the Neurogenins (NGNs) and MASH-1, respectively (Fode, C., Gradwohl, G., Morin, X., Dierich, A., LeMeur, M., Goridis, C. and Guillemot, F. (1998) Neuron 20, 483-494; Guillemot, F., Lo, L.-C., Johnson, J. E., Auerbach, A., Anderson, D. J. and Joyner, A. L. (1993) Cell 75, 463-476; Ma, Q., Chen, Z. F., Barrantes, I. B., de la Pompa, J. L. and Anderson, D. J. (1998 Neuron 20, 469-482). We have cloned two chick NGNs and found that they are expressed in a subset of neural crest cells early in their migration. Ectopic expression of the NGNs in vivo biases migrating neural crest cells to localize in the sensory ganglia, and induces the expression of sensory neuron-appropriate markers in non-sensory crest derivatives. Surprisingly, the NGNs can also induce the expression of multiple pan-neuronal and sensory-specific markers in the dermomyotome, a mesodermal derivative. Taken together, these data suggest that a subset of neural crest cells may already be specified for a sensory neuron fate early in migration, as a consequence of NGN expression.

Angiogenesis is involved in the pathogenesis of inflammatory arthritis, but little is known about the role of lymphangiogenesis in this setting. Here, we examined whether tumor necrosis factor (TNF) stimulates osteoclast precursors (OCPs) to produce the lymphatic growth factor, vascular endothelial growth factor-C (VEGF-C), and induce lymphangiogenesis. We used TNF-transgenic (Tg) mice and mice with serum-induced arthritis. OCPs were purified by fluorescence-activated cell sorting of CD11b+/Gr-1-/lo blood or bone marrow cells and subjected to microarray analysis or were generated from spleen or joint cells and treated with TNF. Expression of VEGFs was analyzed and examined by real-time reverse transcription-polymerase chain reaction and Western blotting. Immunostaining and magnetic resonance imaging were used to quantify lymphatic vessels and volumes of synovium and draining lymph nodes. TNF stimulated VEGF-C expression by OCPs and increased nuclear factor-kappa B (NF-kappaB) binding to an NF-kappaB sequence in the VEGF-C promoter. OCPs from joints of TNF-Tg mice express high levels of VEGF-C. Lymphatic vessel numbers and size were markedly increased in joint sections of TNF-Tg mice and mice with serum-induced arthritis. The severity of synovitis correlated with draining lymph node size. In summary, TNF induces OCPs to produce VEGF-C through NF-kappaB, leading to significantly increased lymphangiogenesis in joints of arthritic mice. The lymphatic system may play an important role in the pathogenesis of inflammatory arthritis.