Interventions for hirsutism (excluding laser and photoepilation therapy alone)

BACKGROUND Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

Recent Advances in Adaptive Sampling and Reconstruction for Monte Carlo Rendering

Monte Carlo integration is firmly established as the basis for most practical realistic image synthesis algorithms because of its flexibility and generality. However, the visual quality of rendered images often suffers from estimator variance, which appears as visually distracting noise. Adaptive sampling and reconstruction algorithms reduce variance by controlling the sampling density and aggregating samples in a reconstruction step, possibly over large image regions. In this paper we survey recent advances in this area. We distinguish between “a priori” methods that analyze the light transport equations and derive sampling rates and reconstruction filters from this analysis, and “a posteriori” methods that apply statistical techniques to sets of samples to drive the adaptive sampling and reconstruction process. They typically estimate the errors of several reconstruction filters, and select the best filter locally to minimize error. We discuss advantages and disadvantages of recent state-of-the-art techniques, and provide visual and quantitative comparisons. Some of these techniques are proving useful in real-world applications, and we aim to provide an overview for practitioners and researchers to assess these approaches. In addition, we discuss directions for potential further improvements.

THE RELATIONSHIP BETWEEN THE RHEOENCEPHALOGRAM AND CEREBRAL BLOOD FLOW

The rheoencephalogram (REG) is the change in the electrical impedance of the head that occurs with each heart beat. Without knowledge of the relationship between cerebral blood flow (Q) and the REG, the utility of the REG in the study of the cerebral vasculature is greatly limited. The hypothesis is that the relationship between the REG and Q when venous outflow is nonpulsatile is^ (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)^ where K is a proportionality constant and Q is the mean Q.^ Pulsatile CBF was measured in the goat via a chronically implanted electromagnetic flowmeter. Electrodes were implanted in the ipsilateral cerebral hemisphere, and the REG was measured with a two electrode impedance plethysmograph. Measurements were made with the animal's head elevated so that venous flow pulsations were not transmitted from the heart to the cerebral veins. Measurements were made under conditions of varied cerebrovascular resistance induced by altering blood CO(,2) levels and under conditions of high and low cerebrospinal fluid pressures. There was a high correlation (r = .922-.983) between the REG calculated from the hypothesized relationship and the measured REG under all conditions.^ Other investigators have proposed that the REG results from linear changes in blood resistivity proportional to blood velocity. There was little to no correlation between the measured REG and the flow velocity ( r = .022-.306). A linear combination of the flow velocity and the hypothesized relationship between the REG and Q did not predict the measured REG significantly better than the hypothesized relationship alone in 37 out of 50 experiments.^ Jacquy proposed an index (F) of cerebral blood flow calculated from amplitudes and latencies of the REG. The F index was highly correlated (r = .929) with measured cerebral blood flow under control and hypercapnic conditions, but was not as highly correlated under conditions of hypocapnia (r = .723) and arterial hypotension (r = .681).^ The results demonstrate that the REG is not determined by mean cerebral blood flow, but by the pulsatile flow only. Thus, the utility of the REG in the determination of mean cerebral blood flow is limited. ^

The association between uterus shape and development of chronic conditions in a retrospective corhort of diethylstilbestrol-exposed women in Minnesota and Texas

Diethylstilbestrol (DES) exposed women are well known to be at increased risk of gynecologic cancers and infertility. Infertility may result from DES associated abnormalities in the shape of women's uteri, yet little research has addressed the effect of uterine abnormalities on risk of infertility and reproductive tract infection. Changes in uterine shape may also influence the risk of autoimmune disease and women's subsequent mental health. A sample of consenting women exposed in utero to hormone who were recruited into the DESAD project, underwent hysterosalpingogram (HSG) from 1978 to 1984. These women also completed a comprehensive health questionnaire in 1994 which included women's self-reports of chronic conditions. HSG data were used to categorize uterine shape abnormalities as arcuate shape, hypoplastic, wide lower segment, and constricted. Women were recruited from two of the four DESAD study sites in Houston (Baylor) and Minnesota (Mayo). All women were DES-exposed. Adjusted relative risk estimates were calculated comparing the range of abnormal uterine shaped to women with normal shaped uteri for each of the four outcomes: infertility, reproductive tract infection, autoimmune disease and depressive symptoms. Only the arcuate shape (n=80) was associated with a higher risk of infertility (relative risk [RR]= 1.53, 95% CI = 1.09, 2.15) as well as reproductive tract infection (RR= 1.74, 95% CI = 1.11, 2.73). In conclusion, DES-associated arcuate shaped uteri appeared to be associated with the higher risk of a reproductive tract infection and infertility while no other abnormal uterine shapes were associated with these two outcomes.^

Hazardous air pollutants and childhood lymphohematopoietic cancer in Southeast Texas, 1995--2004

Southeast Texas, including Houston, has a large presence of industrial facilities and has been documented to have poorer air quality and significantly higher cancer rates than the remainder of Texas. Given citizens’ concerns in this 4th largest city in the U.S., Mayor Bill White recently partnered with the UT School of Public Health to determine methods to evaluate the health risks of hazardous air pollutants (HAPs). Sexton et al. (2007) published a report that strongly encouraged analytic studies linking these pollutants with health outcomes. In response, we set out to complete the following aims: 1. determine the optimal exposure assessment strategy to assess the association between childhood cancer rates and increased ambient levels of benzene and 1,3-butadiene (in an ecologic setting) and 2. evaluate whether census tracts with the highest levels of benzene or 1,3-butadiene have higher incidence of childhood lymphohematopoietic cancer compared with census tracts with the lowest levels of benzene or 1,3-butadiene, using Poisson regression. The first aim was achieved by evaluating the usefulness of four data sources: geographic information systems (GIS) to identify proximity to point sources of industrial air pollution, industrial emission data from the U.S. EPA’s Toxic Release Inventory (TRI), routine monitoring data from the U.S. EPA Air Quality System (AQS) from 1999-2000 and modeled ambient air levels from the U.S. EPA’s 1999 National Air Toxic Assessment Project (NATA) ASPEN model. Further, once these four data sources were evaluated, we narrowed them down to two: the routine monitoring data from the AQS for the years 1998-2000 and the 1999 U.S. EPA NATA ASPEN modeled data. We applied kriging (spatial interpolation) methodology to the monitoring data and compared the kriged values to the ASPEN modeled data. Our results indicated poor agreement between the two methods. Relative to the U.S. EPA ASPEN modeled estimates, relying on kriging to classify census tracts into exposure groups would have caused a great deal of misclassification. To address the second aim, we additionally obtained childhood lymphohematopoietic cancer data for 1995-2004 from the Texas Cancer Registry. The U.S. EPA ASPEN modeled data were used to estimate ambient levels of benzene and 1,3-butadiene in separate Poisson regression analyses. All data were analyzed at the census tract level. We found that census tracts with the highest benzene levels had elevated rates of all leukemia (rate ratio (RR) = 1.37; 95% confidence interval (CI), 1.05-1.78). Among census tracts with the highest 1,3-butadiene levels, we observed RRs of 1.40 (95% CI, 1.07-1.81) for all leukemia. We detected no associations between benzene or 1,3-butadiene levels and childhood lymphoma incidence. This study is the first to examine this association in Harris and surrounding counties in Texas and is among the first to correlate monitored levels of HAPs with childhood lymphohematopoietic cancer incidence, evaluating several analytic methods in an effort to determine the most appropriate approach to test this association. Despite recognized weakness of ecologic analyses, our analysis suggests an association between childhood leukemia and hazardous air pollution.^

Plasma homocysteine levels and Alzheimer's Disease: A systematic review

Objective. To systematically review studies published in English on the relationship between plasma total homocysteine (Hcy) levels and the clinical and/or postmortem diagnosis of Alzheimer's disease (AD) in subjects who are over 60 years old.^ Method. Medline, PubMed, PsycINFO and Academic Search Premier, were searched by using the keywords "homocysteine", "Alzheimer disease" and "dementia", and "cognitive disorders". In addition, relevant articles in PubMed using the "related articles" link and by cross-referencing were identified. The study design, study setting and study population, sample size, the diagnostic criteria of the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA), and description of how Hcy levels were measured or defined had to have been clearly stated. Empirical investigations reporting quantitative data on the epidemiology of the relationship between plasma total Hcy (exposure factor) and AD (outcome) were included in the systematic review.^ Results. A total of 7 studies, which included a total of 2,989 subjects, out of 388 potential articles met the inclusion criteria: four case control and three cohort studies were identified. All 7 studies had association statistics, such as the odds ratio (OR), the relative rates (RR), and the hazard ratio (HR) of AD, examined using multivariate and logistic regression analyses. Three case - comparison studies: Clarke et al. (1998) (OR: 4.5, 95% CI.: 2.2 - 9.2); McIlroy et al. (2002) (OR: 2.9, 95% CI.: 1.00–8.1); Quadri et al. (2004) (OR: 3.7, 95% CI.: 1.1 - 13.1), and two cohort studies: Seshadri et al. (2002) (RR: 1.8, 95% CI.: 1.3 - 2.5); Ravaglia et al. (2005) (HR: 2.1, 95% CI.: 1.7 - 3.8) found a significant association between serum total Hcy and AD. One case-comparison study, Miller et al. (2002) (OR: 2.2, 95% C.I.: 0.3 -16), and one cohort study, Luchsinger et al. (2004) (HR: 1.4, 95% C.I.: 0.7 - 2.3) failed to reject H0.^ Conclusions. The purpose of this review is to provide a thorough analysis of studies that examined the relationship between Hcy levels and AD. Five studies showed a positive statistically significant association between elevated total Hcy values and AD but the association was not statistically significant in two studies. Further research is needed in order to establish evidence of the strong, consistent association between serum total Hcy and AD as well as the presence of the appropriate temporal relationship. To answer these questions, it is important to conduct more prospective studies that examine the occurrence of AD in individuals with and without elevated Hcy values at baseline. In addition, the international standardization of measurements and cut-off points for plasma Hcy levels across laboratories is a critical issue to be addressed for the conduct of future studies on the topic.^

Enlarged tracheoesophageal puncture: A systematic review and retrospective analysis

Background. An enlarged tracheoesophageal puncture (TEP) results in aspiration around the voice prosthesis (VP) and may lead to pneumonia. The aims of this research were: (1) to conduct a systematic review and meta-analysis on enlarged TEP; (2) to analyze preoperative, perioperative, and postoperative risk factors for enlarged TEP; and (3) to evaluate control of leakage around the VP using conservative treatments and adverse events in patients with enlarged TEP.^ Methods. A systematic review was conducted (1978-2008). A summary risk estimate was calculated using a random-effects meta-analysis model. A retrospective cohort study was completed. Patients who underwent total laryngectomy and TEP at The University of Texas M. D. Anderson Cancer Center (MDACC) were included. Multiple logistic regression methods were used to assess risk factors for enlargement. Descriptive and bivariate statistics were calculated to evaluate outcomes and adverse events. Results: Twenty-seven manuscripts were included in the systematic review. The summary risk estimate of enlarged TEP/leakage around the VP was 7.2% (95% CI: 4.8%-9.6%). Temporary VP removal and TEP-site injections were the most commonly reported treatments. Neither prosthetic diameter (p=0.076) nor timing of TEP (p=0.297) significantly increased risk of enlargement per stratified analyses of published outcomes. The cumulative incidence of enlarged TEP was 18.6% (36/194, 95% CI: 13.0%-24.1%) in the MDACC cohort. Enlarged TEP occurred exclusively in irradiated patients. Adjusting for length of follow-up and timing of TEP, advanced nodal disease (ORadjusted: 4.3, 95% CI: 1.0-19.1), stricture (ORadjusted : 3.2, 95% CI: 1.2-8.6), and locoregional recurrence/distant metastasis after laryngectomy (ORadjusted: 6.2, 95% CI: 2.3-16.4) increased risk of enlarged TEP. At last follow-up, conservative methods controlled leakage around the VP in 81% (29/36) of patients. Unresolved leakage was associated with recurrent cancer (p=0.081) and TEP-site irregularity (p=0.003). Relative to those without enlargement, enlarged TEP patients had significantly higher risk of pneumonia (RR: 3.4, 95% CI: 1.9-6.2).^ Conclusions. These data establish that enlarged TEP poses serious health risks, and provide insight into medical and oncologic factors that may contribute to development of this complication. In addition, this research supports the use of conservative treatments to address leakage after enlarged TEP in lieu of complete TEP closure.^

The relationship between premature rupture of the membranes and sepsis in preterm neonates

This investigation was designed as a hospital-based, historical cohort study. The objective of the study was to determine the association between premature rupture of the membranes (PROM) and its duration on neonatal sepsis, infection, and mortality. Neonates born alive with gestational ages between 25 and 35 weeks from singleton pregnancies complicated by PROM were selected. Each of the 507 neonates was matched on gestational age, gender, ethnicity, and month of birth with a neonate without the complication of PROM.^ Data were abstracted from deliveries between January 1979 and December 1985 describing the mother's demographics, labor and delivery treatments and complications, the neonate's demographics, infection status, and medical care. The matched pairs analysis reveals a significant increase in risk of neonatal sepsis (RR = 3.5) and neonatal infection (RR = 2.4) among preterm births complicated by PROM, with a PROM exposure contributing an excess 4 to 5 cases of sepsis per 100 infants (RD = 0.04 for infection and RD = 0.05 for sepsis). Generally PROM remains an important risk factor for sepsis and infection when controlling for various other characteristics, and the risk difference remains constant.^ PROM was not significantly associated with neonatal mortality (RR = 1.02). There is an increase in risk difference for mortality associated with PROM among septic and infected infants, but it is not significant.^ A clear increase in risk of sepsis and infection from PROM occurs when durations of PROM are long (more than 48 hours), e.g., for sepsis the RR is 2.42 for short durations and RR is 6.0 for long durations. No such risk with long duration appears for neonatal mortality.^ This study indicates the importance of close observation of neonates with PROM for sepsis and infection so treatment can be initiated early. However, prematurity is the major risk for sepsis and the practice of early delivery to avoid prolonged durations of PROM does not alter the magnitude of risk. The greatest protection against these infection complications was provided when the neonate weighed over 1500 grams or had more than 33 weeks gestation. ^

Effects of breastfeeding and naturally acquired immunity on infection with {\it Giardia lamblia}: A study in a cohort of Mexican infants

Giardia lamblia is one of the most common causes of gastrointestinal tract infection among young children worldwide. Yet host protection against this parasite and the effect of infection with Giardia on infant growth are poorly understood. It was hypothesized that among young children, protection against infection with Giardia is afforded by breastfeeding and previous infection with the parasite and further, that infection with Giardia decreases growth velocity. From 4/88 to 4/90, 197 infants in a poor area of Mexico City were followed from 0 to 18 months of age, with stool specimens, symptoms and feeding status data collected weekly. A total of 6,031 stool specimens were tested for Giardia antigen by enzyme-linked immunosorbent assay. There were 1.0 Giardia infections per child-year; 25% were symptomatic and 54% lasted more than 1 month; 94 infants had 1, and 33 had 2 or more infections. Breastfeeding status was coded and analyzed for each child-week of follow up. 91% of study infants were breastfed from birth, 57% at 6 months and 38% at 12 months of age. Rate ratios for non-breastfeeding adjusted for confounding factors were calculated from stratified analyses and the Cox proportional hazards model. Not breastfeeding was a significant risk factor for first infection with Giardia vs. any breastfeeding (adjusted RR = 1.8; 1.1, 2.8) at all ages; a dose response was demonstrated by degree of breastfeeding. The adjusted rate ratio for non-breastfeeding vs. partial breastfeeding was 1.6 (1.03, 2.6) and for non-breastfeeding vs. complete breastfeeding was 4.7 (1.4, 15.9). Among Giardia infected infants, breastfeeding did not protect against diarrheal symptoms or shorten the duration of carriage. First and repeat infections with Giardia did not differ in duration or the percent symptomatic. The analysis of growth and Giardia infection was inconclusive but suggested that a history of Giardia infection might be associated with decreased weight velocity, while an immediate chronic infection might be associated with increased weight velocity. In summary, these data indicate that breastfeeding protects infants against infection with Giardia; provide no evidence of protection against repeat infections resulting from a prior infection and suggest but do not establish that a history of Giardia infection might be associated with decreased growth in young children. ^

Penetrating injuries of the thorax and abdomen: Type of medical-care institution and case fatality

The purpose of this study was to determine, for penetrating injuries (gunshot, stab) of the chest/abdomen, the impact on fatality of treatment in trauma centers and shock trauma units compared with general hospitals. Medical records of all cases of penetrating injury limited to chest/abdomen and admitted to and discharged from 7 study facilities in Baltimore city 1979-1980 (n = 581) were studied: 4 general hospitals (n = 241), 2 area-wide trauma centers (n = 298), and a shock trauma unit (n = 42). Emergency center and transferred cases were not studied. Anatomical injury severity, measured by modified Injury Severity Score (mISS), was a significant prognostic factor for death, as were cardiovascular shock (SBP $\le$ 70), injury type (gunshot vs stab), and ambulance/helicopter (vs other) transport. All deaths occurred in cases with two or more prognostic factors. Unadjusted relative risks of death compared with general hospitals were 4.3 (95% confidence interval = 2.2, 8.4) for shock trauma and 0.8 (0.4, 1.7) for trauma centers. Controlling for prognostic factors by logistic regression resulted in these relative risks: shock trauma 4.0 (0.7, 22.2), and trauma centers 0.8 (0.2, 3.2). Factors significantly associated with increased risk had the following relative risks by multiple logistic regression: SBP $\le$ 70 (RR = 40.7 (11.0, 148.7)), highest mISS (42 (7.7, 227)), gunshot (8.4 (2.1, 32.6)), and ambulance/helicopter transport (17.2 (1.3, 228.1)). Controlling for age, race, and gender did not alter results significantly. Actual deaths compared with deaths predicted from a multivariable model of general-hospital cases showed 3.7 more than predicted deaths in shock trauma (SMR = 1.6 (0.8, 2.9)) and 0.7 more than predicted deaths in area-wide trauma centers (SMR = 1.05 (0.6, 1.7)). Selection bias due to exclusion of transfers and emergency center cases, and residual confounding due to insufficient injury information, may account for persistence of adjusted high case fatality in shock trauma. Studying all cases prospectively, including emergency center and transferred cases, is needed. ^

The use of invasive myocardial revascularization procedures following myocardial infarction and the effectiveness of these procedures in the biethnic community of Nueces County, Texas, 1988--1991

High levels of poverty and unemployment, and low levels of health insurance coverage may pose barriers to obtaining cardiac care by Mexican Americans. We undertook this study to investigate differences in the use of invasive myocardial revascularization procedures received within the 4-month period following hospitalization for a myocardial infarction (MI) between Mexican Americans and non-Hispanic whites in the Corpus Christi Heart Project (CCHP). The CCHP is a population-based surveillance program for hospitalized MI, percutaneous transluminal coronary angioplasty (PTCA), and aortocoronary bypass surgery (ACBS). Medical record data were available for 1706 patients identified over a three-year period. Mexican Americans had significantly lower rates of receiving a PTCA following MI than non-Hispanic Whites (RR: 0.56, 95% CI: 0.44-0.70). No meaningful ethnic difference was seen in the rates of ACBS use. History of PTCA use appeared to interact with ethnicity. Among patients without a history of PTCA use, Mexican Americans were less likely to receive a PTCA than non-Hispanic whites (RR: 0.59; 95% CI: 0.46-0.76). Among patients with a history of PTCA use, however, Mexican Americans were more likely to receive a PTCA than non-Hispanic whites (RR: 1.47; 95% CI: 0.75-2.87).^ Differences in the effectiveness of a first-time PTCA and first-time ACBS between Mexican Americans and non-Hispanic whites in the CCHP were also investigated. Mexican Americans were more likely to receive a 2nd PTCA (RR: 1.56, 95% CI: 1.11-2.17) and suffer a subsequent MI (RR: 1.42, 95% CI: 1.03-1.96) following a first-time PTCA than non-Hispanic whites. No meaningful ethnic differences were found in the rates of death and rates of ACBS following a first-time PTCA. Also, no significant ethnic differences were found in the rates of any of the events following a first-time ACBS. After adjusting for potential demographic, socioeconomic, clinical and angiographic confounders using Cox regression analysis, Mexican Americans were still more likely to receive a 2nd PTCA (HR: 1.38; 95% CI: 0.99-1.93) following a first-time PTCA than non-Hispanic whites. A significant difference in the rates of a subsequent MI following a first-time PTCA persisted (HR: 1.39, 95% CI: 1.01-1.93). (Abstract shortened by UMI.) ^

PRETERM BIRTH AND OCCUPATIONAL PHYSICAL ACTIVITY: A CASE-CONTROL STUDY OF THE RELATIONSHIP BETWEEN LENGTH OF GESTATION AND THE PHYSICAL DEMAND OF U.S. ARMY MILITARY OCCUPATIONAL SPECIALTIES (UNITED STATES)

A case-control study has been conducted examining the relationship between preterm birth and occupational physical activity among U.S. Army enlisted gravidas from 1981 to 1984. The study includes 604 cases (37 or less weeks gestation) and 6,070 controls (greater than 37 weeks gestation) treated at U.S. Army medical treatment facilities worldwide. Occupational physical activity was measured using existing physical demand ratings of military occupational specialties.^ A statistically significant trend of preterm birth with increasing physical demand level was found (p = 0.0056). The relative risk point estimates for the two highest physical demand categories were statistically significant, RR's = 1.69 (p = 0.02) and 1.75 (p = 0.01), respectively. Six of eleven additional variables were also statistically significant predictors of preterm birth: age (less than 20), race (non-white), marital status (single, never married), paygrade (E1 - E3), length of military service (less than 2 years), and aptitude score (less than 100).^ Multivariate analyses using the logistic model resulted in three statistically significant risk factors for preterm birth: occupational physical demand; lower paygrade; and non-white race. Controlling for race and paygrade, the two highest physical demand categories were again statistically significant with relative risk point estimates of 1.56 and 1.70, respectively. The population attributable risk for military occupational physical demand was 26%, adjusted for paygrade and race; 17.5% of the preterm births were attributable to the two highest physical demand categories. ^

OCCUPATIONAL CAUSES OF LUNG CANCER IN NEW MEXICO'S ANGLOS AND HISPANICS

Although, elevated risk for lung cancer has been associated with certain industries and occupations in previous studies, the lack of cigarette smoking information in many of these investigations resulted in estimates that could not be adjusted for the effects of smoking. To determine lung cancer risk due to occupation and smoking, for New Mexico's Anglos and Hispanics, a population-based case-control study was conducted. Incident cases diagnosed 1980-1982, and controls from the general population, were interviewed for lifetime occupational and smoking histories. Specific high risk industries and occupations were identified in advance and linked with industrial and occupational codes for hypotheses-testings. Significantly elevated risks were found for welders (RR = 3.5) and underground miners (RR = 2.0) with adjustment for smoking. Because shipbuilding was the industry of employment for only five of the 18 cases who were welders, exposures other than asbestos could be causal agents. Among the underground for only five of the 18 cases who were welders, exposures other than asbestos could be causal agents. Among the underground miners, uranium, copper, lead and zinc, coal, and potash mining industries were represented. Low prevalence of employment in some of the industries and occupations of interest resulted in inconclusive results. ^

Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis

Hepatitis B virus (HBV) is a significant cause of liver diseases and related complications worldwide. Both injecting and non-injecting drug users are at increased risk of contracting HBV infection. Scientific evidence suggests that drug users have subnormal response to HBV vaccination and the seroprotection rates are lower than that in the general population; potentially due to vaccine factors, host factors, or both. The purpose of this systematic review is to examine the rates of seroprotection following HBV vaccination in drug using populations and to conduct a meta-analysis to identify the factors associated with varying seroprotection rates. Seroprotection is defined as developing an anti-HBs antibody level of ≥ 10 mIU/ml after receiving the HBV vaccine. Original research articles were searched using online databases and reference lists of shortlisted articles. HBV vaccine intervention studies reporting seroprotection rates in drug users and published in English language during or after 1989 were eligible. Out of 235 citations reviewed, 11 studies were included in this review. The reported seroprotection rates ranged from 54.5 – 97.1%. Combination vaccine (HAV and HBV) (Risk ratio 12.91, 95% CI 2.98-55.86, p = 0.003), measurement of anti-HBs with microparticle immunoassay (Risk ratio 3.46, 95% CI 1.11-10.81, p = 0.035) and anti-HBs antibody measurement at 2 months after the last HBV vaccine dose (RR 4.11, 95% CI 1.55-10.89, p = 0.009) were significantly associated with higher seroprotection rates. Although statistically nonsignificant, the variables mean age>30 years, higher prevalence of anti-HBc antibody and anti-HIV antibody in the sample population, and current drug use (not in drug rehabilitation treatment) were strongly associated with decreased seroprotection rates. Proportion of injecting drug users, vaccine dose and accelerated vaccine schedule were not predictors of heterogeneity across studies. Studies examined in this review were significantly heterogeneous (Q = 180.850, p = 0.000) and factors identified should be considered when comparing immune response across studies. The combination vaccine showed promising results; however, its effectiveness compared to standard HBV vaccine needs to be examined systematically. Immune response in DUs can possibly be improved by the use of bivalent vaccines, booster doses, and improving vaccine completion rates through integrated public programs and incentives.^

Trastuzumab use and risk of congestive heart failure in older breast cancer patients

Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^