Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome.

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150-300 µm; small, <150 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.

Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians.

AIM: To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients. METHODS: A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis. RESULTS: Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH. CONCLUSION: Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.

Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda.

BACKGROUND & AIMS: Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. METHODS: We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. RESULTS: The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95-5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. CONCLUSIONS: Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754.

Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis.

UNLABELLED: Changes in synapse structure occur in frontal neocortex with HIV encephalitis (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A postmortem survey was conducted to determine if mRNAs involved in synaptic transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin mRNA (PENK) was significantly decreased in a sampling of 446 brain specimens from HIV-1 infected people compared to 67 HIV negative subjects. Decreased DLPFC PENK was most evident in subjects with HIVE and/or increased expression of interferon regulatory factor 1 mRNA (IRF1). Type 2 dopamine receptor mRNA (DRD2L) was decreased significantly, but not in the same set of subjects with PENK dysregulation. DRD2L downregulation occurred primarily in the subjects without HIVE or neurocognitive impairment. Subjects with neurocognitive impairment often failed to significantly downregulate DRD2L and had abnormally high IRF1 expression. CONCLUSION: Dysregulation of synaptic preproenkephalin and DRD2L in frontal neocortex can occur with and without neurocognitive impairment in HIV-infected people. Downregulation of DRD2L in the prefrontal cortex was associated with more favorable neuropsychological and neuropathological outcomes; the failure to downregulate DRD2L was significantly less favorable. PENK downregulation was related neuropathologically to HIVE, but was not related to neuropsychological outcome independently. Emulating endogenous synaptic plasticity pharmacodynamically could enhance synaptic accommodation and improve neuropsychological and neuropathological outcomes in HIV/AIDS.

Implementation of health information technology to maximize efficiency of resource utilization in a geographically dispersed prenatal care delivery system.

This study investigated the utilization of health information technology (HIT) to enhance resource utilization in a geographically dispersed tertiary care system with extensive outpatient and delivery services. It was initiated as a result of a systems change implemented after Hurricane Ike devastated southeast Texas. A retrospective database and electronic medical record review was performed, which included data collection from all patients evaluated 18 months prior (epoch I) and 18 months following (epoch II) the landfall of Hurricane Ike. The months immediately following the storm were omitted from the analysis, allowing time to establish a new baseline. We analyzed a total of 21,201 patients evaluated in triage at the University of Texas Medical Branch. Epoch I consisted of 11,280 patients and epoch II consisted of 9922 patients. Using HIT, we were able to decrease the number of visits to triage while simultaneously managing more complex patients in the outpatient setting with no clinically significant change in maternal or fetal outcome. This study developed an innovated model of care using constrained resources while providing quality and safety to our patients without additional cost to the health care delivery system.

Teen dating violence and substance use following a natural disaster: does evacuation status matter?

OBJECTIVES: In September 2008, the Texas coast was directly hit by Hurricane Ike. Galveston Island was flooded by 4.25 m of storm surge, affecting most of the island's housing and infrastructure. The purpose of this study is to examine whether youth who did not evacuate (11 percent), and subsequently were exposed to Hurricane Ike, exhibit higher rates of substance use and physical and sexual teen dating violence (TDV; both perpetration and victimization) when compared with adolescents who did evacuate. SETTING: Public high school in southeast Texas that was in the direct path of Hurricane Ike. PARTICIPANTS: An anonymous survey was conducted in March 2009 to 1,048 high school students who returned to the Galveston Island post-storm (41 percent Hispanic, 23 percent African American, and 27 percent White). MAIN OUTCOME MEASURES: Teen dating violence and substance use. RESULTS: Mantel-Haenszel odds ratios, adjusting for age and ethnicity, were computed. When compared with boys who evacuated, nonevacuating boys were more likely to perpetrate physical dating violence and sexual assault and to be a victim of sexual assault. Nonevacuating boys and girls were more likely to report recent use of excessive alcohol, marijuana, and cocaine than those who did evacuate. CONCLUSIONS: School personnel, medical personnel, and mental health service providers should consider screening for evacuation status in seeking to identify those adolescents who most need services after a natural disaster. In addition to addressing internalized emotions and psychological symptoms associated with experiencing trauma, intervention programs should focus on reducing externalized behavior such as substance use and TDV.

Dating violence and substance use among ethnically diverse adolescents.

Teen dating violence is a serious public health concern with numerous and long-lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the association between dating violence victimization and the use of a variety of licit and illicit substances among 1,565 ethnically diverse and economically disadvantaged high school students in southeast Texas. Past year dating violence victimization was reported by 14.1% of boys and 11.3% of girls. Compared to their nonabused counterparts, youth who experienced dating violence were more likely to smoke cigarettes, drink alcohol, binge drink alcohol, sniff glue to get high, use marijuana, use ecstasy, use Vicodin, and use Xanax. However, with the exception of alcohol and cigarettes, all substances were reduced to nonsignificance in multivariate analyses. No differences were found in the rate of dating violence between African American, White, and Hispanic adolescents.

Smokeless tobacco use among military flight personnel: a survey of 543 aviators.

INTRODUCTION: Although there has been a steady decline in smoking rates among adults in the United States in recent years, the consumption of smokeless tobacco (ST) continues to increase. Moreover, ST use in the U.S. military is far higher than in the general population. This study was designed to determine the extent of ST use in a military aviation population and measure users' attitudes toward elements of a proposed cessation program. METHODS: A study was conducted at two naval aviation training wings in western Florida. The target population (N=2233) included flight instructors, students, and staff/support personnel who were rated aviators or flight officers. A total of 543 usable questionnaires were returned, yielding a response rate of 24.3%. RESULTS: There were 71 respondents who reported using ST in the last 30 d (13.1%). This group responded favorably to questions regarding the involvement of both medical and dental health professionals as critical components of an effective ST cessation program. DISCUSSION: This survey provides evidence for a rate of ST use among military aviators that is much higher than the U.S. national civilian average of 3.5%. Drawing upon the background of previous dental health-based studies, we propose augmenting existing tobacco cessation resources by creating separate ST cessation programs to reduce ST use among U.S. military aviators.

Prognostic significance of peritumoral lymphatic vessel density and vascular endothelial growth factor receptor 3 in invasive squamous cell cervical cancer.

Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic metastasis is associated with a poor prognosis. In patients who have undergone a radical hysterectomy, lymphovascular space invasion (LVSI), assessed on hematoxylin and eosin-stained slides, is a major factor for adjuvant therapy in patients with cervical cancer. With the advent of a lymphatic endothelial cell-specific marker, such as D2-40, it is now possible to distinguish between blood and lymphatic space invasion (LSI). In this study, the utility of D2-40 was assessed for the detection of lymphatic vessel density (LVD) and identification of LSI. The expressions of vascular endothelial growth factor receptor-3 (VEGFR-3), VEGF-C, tyrosine receptor kinase-2, and angiopoietin-1 were assessed by immunohistochemical methods on 50 patients with squamous cell carcinoma of the cervix. Clinicopathologic characteristics, including pelvic lymph node metastasis, were correlated with the above histochemical findings. We found that lymphangiogenesis, measured by an increase in peritumoral LVD, was significantly associated with positive lymph node status (P < .005). VEGFR-3 expression was significantly associated with LVD (P < .05). D2-40 staining verified LSI (P = .03) and surpassed that of hematoxylin and eosin-identified LVSI (P = .54). In conclusion, lymphangiogenic markers, specifically LVD quantified by D2-40 and VEGFR-3, are independently associated with LSI and lymph node metastasis in patients with early squamous cell carcinoma of the cervix treated with radical hysterectomy and pelvic lymphadenectomy.

Social Factors Associated with History of Sexual Assault Among Ethnically Diverse Adolescents.

We examine the association of adolescents' self-reported sexual assault victimization with their living arrangements, parent's education, and plans for college. Participants included 1,634 ethnically-diverse and economically-disadvantaged high school students in southeast Texas. Lifetime history of forced sexual assault was reported by 8.3% of girls and 9% of boys. No association with gender, age, or parent's education was detected. However, adolescents in non-traditional households (living with one parent, grandparents, or other) were more likely to report rape than youth living with both parents. Adolescents who were one race/ethnicity were less likely to report being raped than those in the multiple race category. Sexual assault intervention programs should account for a teenager's living situation; and prevention efforts may benefit from targeting individuals in non-traditional households. The lack of an association with either gender or socio-educational status indicates that all children are at risk and that school-based programs should be broadly targeted.

Correlates of bacterial pneumonia hospitalizations in elders, Texas border.

BACKGROUND: Immunization preventable bacterial pneumonia is an Agency for Healthcare Research and Quality (AHRQ) prevention quality indicator of health care. This study explored associations of individual and county correlates with bacterial pneumonia hospitalization rates for elders residing in 32 Texas counties bordering Mexico. METHODS: We estimated baseline rates from Texas Health Care Information Collection's hospital discharge data for 1999-2001, and population counts from the 2000 U.S. Census. RESULTS: The rate among the total Texas border population was 500/10,000, three times the national rate. Elders 75+, males, and Latinos had the highest rates. An increase of 1 primary care physician per 1000 population is associated with a decrease in pneumonia-related hospitalization rates by 33%, while each 10% increase in Latinos is associated with a 0.1% rate increase. DISCUSSION: This baseline bacterial pneumonia hospitalization study demonstrates a systematic approach to estimate county rates, a process that could lead to improved outcomes through effective community interventions. Methodology demonstrates how publicly available hospital discharge data can be used by communities to better measure and improve quality of health care.

Reducing the effects of lead-time bias, length bias and over-detection in evaluating screening mammography: a censored bivariate data approach.

Measuring the benefit of screening mammography is difficult due to lead-time bias, length bias and over-detection. We evaluated the benefit of screening mammography in reducing breast cancer mortality using observational data from the SEER-Medicare linked database. The conceptual model divided the disease duration into two phases: preclinical (T(0)) and symptomatic (T(1)) breast cancer. Censored information for the bivariate response vector ( T(0), T(1)) was observed and used to generate a likelihood function. However, the contribution to the likelihood function for some observations could not be calculated analytically, thus, censoring boundaries for these observations were modified. Inferences about the impact of screening mammography on breast cancer mortality were made based on maximum likelihood estimates derived from this likelihood function. Hazard ratios (95% confidence intervals) of 0.54 (0.48-0.61) and 0.33 (0.26- 0.42) for single and regular users (vs. non-users), respectively, demonstrated a protective effect of screening mammography among women 69 years and older. This method reduced the impact of lead-time bias, length bias and over-detection, which biased the estimated hazard ratios derived from standard survival models in favour of screening.

Mammography use among older Mexican-American women: correcting for over-reports of breast cancer screening.

OBJECTIVES: To determine the accuracy of self-reported mammography use and generate a correction factor that adjusts for reporting errors among Mexican-American women. DESIGN: Self-reported mammography use was compared with a medical chart review. PARTICIPANTS: A random sample of 199 Mexican-American women aged 50-74 in southeast Texas. MAIN OUTCOME MEASURES: Self-reported mammography use for the preceding 2 years and mammography use determined by medical chart review. RESULTS: Positive and negative predictive values of mammography self-reports in the previous 2 years were 73.9 and 86.0%, respectively. The correction factor was 79.6%, or approximately 80% of the self-reported mammograms within the preceding 2 years could be verified through medical chart reviews. CONCLUSIONS: Mammography use rates among Mexican-American women were not as high as self-reports indicated. Estimates need to be adjusted downward by approximately 20%.

Evaluating health care performance: strengths and limitations of multilevel analysis.

An increasing number of health services researchers are using multilevel analysis for evaluating health care performance. This method has the distinct advantage of accounting for within-provider correlation among patients. Alternatively, in a similar manner, estimators based on cluster sampling can also adjust for within-provider correlation. Cluster sampling methods do not require assumptions about error distribution as multilevel analysis does. To our knowledge, no comparison has been made between multilevel analysis and cluster sampling estimators in evaluating health care performance using either a simulated or real dataset. In this paper, we compare the cluster sampling estimators to multilevel estimators in evaluating screening mammography performance using Medicare claims data. We also discuss the strengths and limitations of multilevel analysis in profiling health care providers with small caseloads.

Variation in false-positive rates of mammography reading among 1067 radiologists: a population-based assessment.

BACKGROUND: The accuracy of mammography reading varies among radiologists. We conducted a population-based assessment on radiologist variation in false- positive rates of screening mammography and its associated radiologist characteristics. METHODS: About 27,394 screening mammograms interpreted by 1067 radiologists were identified from a 5% non-cancer sample of Medicare claims during 1998-1999. The data were linked to the American Medical Association Masterfile to obtain radiologist characteristics. Multilevel logistic regression models were used to examine the radiologist variation in false-positive rates of screening mammography and the associated radiologist characteristics. RESULTS: Radiologists varied substantially in the false-positive rates of screening mammography (ranging from 1.5 to 24.1%, adjusting for patient characteristics). A longer time period since graduation is associated with lower false-positive rates (odds ratio [OR] for every 10 years increase: 0.87, 95% Confidence Interval [CI], 0.81-0.94) and female radiologists had higher false-positive rates than male radiologists (OR = 1.25, 95% CI, 1.05-1.49), adjusting for patient and other radiologist characteristics. The unmeasured factors contributed to about 90% of the between-radiologist variance. CONCLUSIONS: Radiologists varied greatly in accuracy of mammography reading. Female and more recently trained radiologists had higher false-positive rates. The variation among radiologists was largely due to unmeasured factors, especially unmeasured radiologist factors. If our results are confirmed in further studies, they suggest that system-level interventions would be required to reduce variation in mammography interpretation.

Correlation of different 5-FU regimens and time to surgery with pathological complete response in locally advanced rectal cancer patients treated by pre-operative chemo-radiation.

The best pre-operative chemo-radiation regimen has still to be defined for patients with rectal cancer. We retrospectively performed a study comprised of 26 patients with T3/4 adenocarcinoma of the rectum. Eleven patients received concurrent protracted venous 5-FU infusion (PVI), 11 had bolus, 1 had 4-day infusions, and 3 did not receive concurrent chemotherapy. All patients underwent surgical resection. Different variables were analyzed in relation to pathologic complete response (pCR) and survival. The use of PVI is associated with a higher pCR rate (45.5% vs. 6.7%, p = 0.054) and a trend towards less proportion of death (p =0.091), but no difference in overall survival (p = 0.439). Patients in the PVI group received a higher total 5-FU dose during radiation (p < 0.001) and had a longer delay between radiation and surgery (p = 0.002). Further study with a larger patient population is needed to confirm our observation.

Diagnostic utility of cell cycle and apoptosis regulatory proteins in verrucous squamous carcinoma.

A major problem in the diagnosis of verrucous squamous cell carcinoma is the lack of readily reproducible objective criteria for distinguishing this malignant lesion from reactive epithelial hyperplasia. Both lesions are characterized by thickened (well-differentiated) squamous epithelium without cellular atypia and subjacent stroma densely infiltrated by lymphocytes and plasma cells. This study was carried out to evaluate the use of cell cycle and apoptosis-related regulatory proteins in the diagnosis of verrucous carcinoma. The study materials consisted of representative formalin-fixed and paraffin-embedded tissue blocks from 19 cases of verrucous carcinoma, 18 classic squamous cell carcinoma, and 14 squamous epithelial hyperplasia (acanthosis). The immunohistochemical expression of the following of cell cycle and apoptosis-related regulatory proteins was evaluated using avidin-biotin complex detection technique: p16, p21, p53, Ki67, and retinoblastoma gene product (RBGP) (also known as retinoblastoma protein [pRb]). Expression of Ki67 was detected only in the single basal layer of the epithelium in all 14 cases of acanthosis. In verrucous carcinoma, Ki67 was detected in basal and suprabasal cells in the lower third of the neoplastic epithelium in 19 of 19 cases (100%). In neoplastic squamous epithelium with frankly invasive squamous cell carcinoma, Ki67 was diffusely expressed throughout the entire thickness of the epithelium as well as in the underlying invasive tumor nests. The pattern of p53 expression was similar to that of Ki67 in all the experimental groups, with a Pearson correlation coefficient of 0.98. In addition, immunohistochemical expression of p53 in the hyperplastic squamous epithelium was very weak, in contrast to the more intense immunoreactivity observed in verrucous carcinoma and classic squamous cell carcinoma. There was an overlapping in the expression of p16, p21, and RGBP in all the experimental groups, being present in more than half the thickness of the epithelium in 50% to 100% cases in each study group. We therefore conclude that the pattern of Ki67 and p53 expression in verrucous carcinoma is readily reproducible and distinctly different from that observed in epithelial hyperplasia and that seen in invasive squamous cell carcinoma. Thus Ki67, and p53 immunostains are reliable adjuncts that may be helpful in resolving diagnostic problems associated with verrucous carcinoma.

Age at death, season, and day of death as indicators of the effect of the back to sleep program on sudden infant death syndrome in the United States, 1992-1999.

BACKGROUND: In June 1992, the American Academy of Pediatrics Task Force on Infant Positioning and Sudden Infant Death Syndrome (SIDS) made its first recommendation concerning placing infants in a supine position. Since the publication of this recommendation, SIDS rates in the United States have declined 44%. Before this recommendation, SIDS had a marked seasonal pattern and was noted to occur more frequently on weekends. OBJECTIVE: The objective of this study was to determine if significant changes in SIDS rates have occurred in age at death (0-27 days vs 1-6 months vs 7-11 months), season of death, and weekday of death since the implementation of the recommendations for supine positioning of infants for sleep. DESIGN: United States natality and mortality data were used for the years 1992 through 1994. United States linked infant birth and death certificate files were used for the years 1995 through 1999. Season of death was calculated from month of death and was ordered for analysis from winter to fall to spring to summer; day of death was ordered from Monday to Sunday and additionally analyzed as weekend (Saturday and Sunday) vs weekday (Monday through Friday). RESULTS: During the 8 years, 28 548 deaths were attributed to SIDS among residents of the United States. The average annual decrease in the SIDS rate for neonates aged 0 to 27 days was 6.6%; for infants aged 1 to 6 months, 9.0%; and for infants aged 7 to 11 months, 6.1%. The average decline in seasonal rates from winter to summer was 11.2% per season. A significant interaction between year of death and season indicated a diminishing rate of seasonal variation. The odds ratio for weekend vs weekday SIDS deaths was 0.98 (95% confidence interval, 0.96-1.01). There was no significant interaction between year of death and weekday of death, which indicates no change in the relationship since the implementation of the supine sleeping recommendations. CONCLUSIONS: These data provide insights into the effect of the supine sleep recommendations on SIDS. The reduction in seasonal variation of SIDS suggests advantages conferred by supine sleeping in colder seasons.