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.

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.

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.

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.

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.

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.

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.

Geographic variations in breast cancer survival among older women: implications for quality of breast cancer care.

BACKGROUND: Breast cancer care, such as utilization of screening procedures and types of treatment received, varies substantially by geographic region of the United States. However, little is known about variations in survival with breast cancer. METHODS: We examined breast cancer incidence, survival, and mortality in the 66 health service areas covered by the Surveillance, Epidemiology, and End Results (SEER) program for women aged 65 and older at diagnosis. Incidence and survival data were derived from SEER, while breast cancer mortality data were from Vital Statistics data. RESULTS: There was considerable variation in breast cancer survival among the 66 health service areas (chi2 = 202.7, p <.0001). There was also significant variation in incidence and mortality from breast cancer. In a partial correlation weighted for the size of the health service area, both incidence (r =.812) and percent 5-year survival (r = -.587) correlate with mortality. In a Poisson regression analysis, the combination of variation in incidence and variation in survival explains 90.9% of the variation in mortality. CONCLUSIONS: There is considerable geographic variation in survival from breast cancer among older women, and this contributes to variation in breast cancer mortality. Geographic variations in breast cancer mortality should diminish as the quality of breast cancer care becomes more standardized.

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.

Social Support and Depression After Cardiac Surgery in Elderly Patients.

Two methods of measuring social support components were compared for their ability to predict depression 6 months after cardiac surgery in older patients (N = 155). Multiple regression models were used to compare summary support measures with subtype measures. A personality inventory was also included to rule out the possibility that significant findings about relationships of depression and social support were due primarily to personality dimensions. In the summary model, only the number of network members seen regularly was associated with less depression. In the subtype model, the number of relatives seen regularly and perceived adequacy of support from friends were associated with less depression, whereas receipt of tangible support was associated with more. When examined together with personality dimensions, both the summary components and subtypes of components of social support were better predictors of depressive symptomatology than the personality dimensions. The results helped confirm the importance of social support factors to the occurrence of depression in elderly patients and suggested that measures of social support subtypes were more informative than summary measures of social support.

Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival.

The relationship of thyroid transcription factor-1 (TTF-1) and HER2/neu expression in non-small cell lung cancer (NSCLC) with multiple parameters including survival were examined. Patients with primary NSCLC who had surgical resection and follow-up of at least 5 years were included in the study. There were 57 patients (38 men and 19 women), 44 to 75 years old (median age, 61 years); 28 patients had adenocarcinoma (AD) and 29 had squamous cell carcinoma. Tumors were examined for TTF-1 and HER2/neu expression using formalin-fixed, paraffin-embedded tissue. Clinical and follow-up data were obtained from the hospital records and Cancer Center database. Representative tumor sections were stained using standard immunohistochemical technique and commercial antibodies for TTF-1 (clone 8G7G3/1, Dako) and HER2/neu (polyclonal, Dako). Tumors were graded as negative (<5%), weak positive (5-49%), and strong positive (>50%), based on the percentage of positively stained tumor cells. Statistical analyses were performed using log-rank test, Pearson and Spearman correlations, and Kaplan-Meier survival curves. TTF-1 expression was seen in 45.6% of all tumors (80% of ADs and 14% of squamous cell carcinomas). Eighteen patients with tumors showing strong TTF-1 expression had significantly better survival compared with the 39 patients whose tumors showed negative or weak TTF-1 expression, although many more of the higher stage AD had strong TTF-1 staining than stage I AD. The TTF-1 expression did not correlate with tumor differentiation and was considered an independent predictor of survival. Seventeen of the 18 tumors with strong TTF-1 expression were ADs. Only eight of 57 (17%) tumors showed HER2/neu expression; seven of these eight were ADs. Although HER2/neu expression and survival did not show correlation, the majority of those ADs with weak or strong HER2/neu staining also had strong TTF-1 staining, were mostly stage I tumors. and had overall longer survival. All patients with stage I disease showed better 5-year survival compared with those with stages II and III. Hispanic patients had significantly worse survival compared with Caucasians and African Americans. The results of this study suggest that strong expression of TTF-1 is an independent predictor of better survival and may be a useful prognostic tool for evaluation of patients with NSCLC.

What was the cause of Franklin Delano Roosevelt's paralytic illness?

In 1921, when he was 39 years of age, Franklin Delano Roosevelt contracted an illness characterized by: fever; protracted symmetric, ascending paralysis; facial paralysis; bladder and bowel dysfunction; numbness; and dysaesthesia. The symptoms gradually resolved except for paralysis of the lower extremities. The diagnosis at the onset of the illness and thereafter was paralytic poliomyelitis. Yet his age and many features of the illness are more consistent with a diagnosis of Guillain-Barré syndrome, an autoimmune polyneuritis. The likelihoods (posterior probabilities) of poliomyelitis and Guillain-Barré syndrome were investigated by Bayesian analysis. Posterior probabilities were calculated by multiplying the prior probability (disease incidence in Roosevelt's age group) by the symptom probability (likelihood of a symptom occurring in a disease). Six of eight posterior probabilities strongly favoured Guillain-Barré syndrome.

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.

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.

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.

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.

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.