Mediating pathways that link adverse childhood experiences with cardiovascular disease.

OBJECTIVES: There is uncertainty about which factors mediate the association between adverse childhood experiences (ACEs) and cardiovascular disease (CVD). This could inform secondary prevention targets. STUDY DESIGN: Mediation analysis of a prospective cohort study. METHODS: English Longitudinal Study of Ageing (ELSA) wave 3 data (2006/7) were used to measure retrospective exposure to 12 individual ACEs and waves 2 to 4 (2004/5 to 2008/9) data to measure current exposure to potential mediators [smoking, physical activity, alcohol consumption, body mass index, depression, and C-reactive protein (CRP)]. Waves 4 to 9 ELSA data (2008/9 to 2018/19) were used to measure incident CVD. Cumulative ACE exposure was categorised into experiencing 0, 1 to 3, or ≥4 individual ACEs. Associations were tested between ACE categories, potential mediators, and incident CVD, to inform which variables were analysed in causal mediation models. RESULTS: The analytical cohort consisted of 4547 participants (56% women), with a mean age of 64 years (standard deviation = 9 years). At least one ACE had been experienced by 45% of the cohort, and 24% developed incident CVD over a median follow-up period of 9.7 years (interquartile range: 5.3-11.4 years). After adjusting for potential confounders, experiencing ≥4 ACEs compared with none was associated with incident CVD [odds ratio (OR): 1.55; 95% confidence interval (CI): 1.10, 2.17], and the association of one to three ACEs compared with none was non-significant (OR: 1.08; 95% CI: 0.93, 1.24). There were two statistically significant mediators of the association between ≥4 ACEs and incident CVD: CRP and depression, which accounted for 10.7% and 10.8% of the association, respectively. CONCLUSIONS: Inflammation and depression partially mediated the association between ACEs and CVD. Targeting these factors may reduce the future incidence of CVD.

Associations among temporal and large artery abnormalities on vascular ultrasound in giant cell arteritis.

Objectives: Giant cell arteritis (GCA) can manifest in cranial and/or extracranial arteries. We investigated the distribution of affected arteries on vascular ultrasound (VUS) among patients with new-onset or prior-onset GCA.Method: We retrospectively studied patients with either new-onset or prior-onset GCA and an abnormal VUS, from 2013 to 2017. Trained vascular technologists imaged the bilateral temporal arteries and carotid, axillary, and subclavian arteries. Vascular medicine physicians interpreted the images. Vasculitis-related abnormalities in individual vessels and their distribution (temporal artery, large artery, or both) were evaluated. Phi coefficients (φ) and Fisher's exact test were used to assess correlations among individual abnormal arteries.Results: Among 66 GCA patients, 28.8% had prior-onset GCA (median duration 17.8 months). Acute arteritis on VUS was observed in the majority of patients with both new-onset (72.3%) and prior-onset GCA (68.4%); the remainder had hyperechoic wall thickening without acute arteritis. Involvement of the temporal arteries only (45.5%) or large arteries only (34.8%) was more common than involvement of both (19.7%); this finding was similar in new-onset and prior-onset GCA. There were moderate positive correlations among temporal artery branches (φ = 0.51-0.58, p < 0.003) and among axillary and subclavian arteries (φ = 0.51-0.77, p < 0.003), and moderate negative correlations between abnormalities in the temporal and large arteries (φ = -0.46 to -0.58, p < 0.003).Conclusion: On VUS, vasculitis-related abnormalities in the temporal arteries only or large arteries only were more common than concurrent temporal and large artery abnormalities in patients with both new-onset GCA and prior-onset GCA.

The impact of life events on later life: a latent class analysis of the English Longitudinal Study of Ageing.

BACKGROUND: Inequalities in life events can lead to inequalities in older age. This research aimed to explore associations between life events reported by older people and quality of life (QoL) and functional ability. METHODS: Participants were grouped according to eight life events: parental closeness, educational opportunities in childhood, financial hardship, loss of an unborn child, bereavement due to war, involvement in conflict, violence and experiencing a natural disaster. Linear and logistic regressions were used to explore associations between these groups and the main outcomes of functional ability and QoL. RESULTS: 7555 participants were allocated to four LCA groups: 'few life events' (n = 6,250), 'emotionally cold mother' (n = 724), 'violence in combat' (n = 274) and 'many life events' (n = 307). Reduced QoL was reported in the 'many life events' (coefficient - 5.33, 95%CI -6.61 to -4.05), 'emotionally cold mother' (-1.89, -2.62 to 1.15) and 'violence in combat' (-1.95, -3.08 to -0.82) groups, compared to the 'few life events' group. The 'many life events' group also reported more difficulty with activities of daily living. CONCLUSIONS: Policies aimed at reducing inequalities in older age should consider events across the life course.

Prescription opioid misuse motive latent classes: outcomes from a nationally representative US sample.

AIMS: Prescription opioid misuse (POM) contributes to a larger opioid crisis in the US and Canada, with over 17 000 US POM-related overdose deaths in 2017. Our aims were to (1) identify specific profiles of respondents based on POM motives using the US National Survey on Drug Use and Health (NSDUH) and (2) compare profile respondents on sociodemographics, substance use and mental and physical health outcomes. METHODS: Analyses included 2017-18 NSDUH respondents with data on POM motives (n = 4810). POM was defined as prescription opioid use in a way not intended by the prescriber, including use without a prescription, in larger amounts or more frequently. Nine POM motives for the most recent episode were assessed, including 'to relieve physical pain' and 'to get high'. Latent classes, based on POM motives, were estimated. Classes were compared on sociodemographics, substance use and physical and mental health outcomes. RESULTS: Eight latent classes were identified (in order of prevalence): pain relief only, relax-pain relief, sleep-pain relief, multi-motive, high, experimenter, emotional coping and dependent/hooked. Compared to the pain relief only group, the high and multi-motive classes had higher odds of all substance use outcomes, with the dependent/hooked class having higher odds on all but one outcome. Six of the eight classes had higher odds of past-year mental health treatment and suicidal ideation than the pain relief only class. CONCLUSIONS: Screening for pain, pain conditions, problematic substance use and psychopathology are recommended in those with any POM. While those in the dependent/hooked, multi-motive and emotional coping classes are most likely to have prescription opioid use disorder (OUD), screening for OUD symptoms in all individuals with POM is also warranted.

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy: a systematic review and economic evaluation.

BACKGROUND: In the UK, prostate cancer (PC) is the most common cancer in men. A diagnosis can be confirmed only following a prostate biopsy. Many men find themselves with an elevated prostate-specific antigen (PSA) level and a negative biopsy. The best way to manage these men remains uncertain. OBJECTIVES: To assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) and enhanced magnetic resonance imaging (MRI) techniques [dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI)] and the clinical effectiveness and cost-effectiveness of strategies involving their use in aiding the localisation of prostate abnormalities for biopsy in patients with prior negative biopsy who remain clinically suspicious for harbouring malignancy. DATA SOURCES: Databases searched--MEDLINE (1946 to March 2012), MEDLINE In-Process & Other Non-Indexed Citations (March 2012), EMBASE (1980 to March 2012), Bioscience Information Service (BIOSIS; 1995 to March 2012), Science Citation Index (SCI; 1995 to March 2012), The Cochrane Library (Issue 3 2012), Database of Abstracts of Reviews of Effects (DARE; March 2012), Medion (March 2012) and Health Technology Assessment database (March 2012). REVIEW METHODS: Types of studies: direct studies/randomised controlled trials reporting diagnostic outcomes. INDEX TESTS: MRS, DCE-MRI and DW-MRI. Comparators: T2-weighted magnetic resonance imaging (T2-MRI), transrectal ultrasound-guided biopsy (TRUS/Bx). Reference standard: histopathological assessment of biopsied tissue. A Markov model was developed to assess the cost-effectiveness of alternative MRS/MRI sequences to direct TRUS-guided biopsies compared with systematic extended-cores TRUS-guided biopsies. A health service provider perspective was adopted and the recommended 3.5% discount rate was applied to costs and outcomes. RESULTS: A total of 51 studies were included. In pooled estimates, sensitivity [95% confidence interval (CI)] was highest for MRS (92%; 95% CI 86% to 95%). Specificity was highest for TRUS (imaging test) (81%; 95% CI 77% to 85%). Lifetime costs ranged from £3895 using systematic TRUS-guided biopsies to £4056 using findings on T2-MRI or DCE-MRI to direct biopsies (60-year-old cohort, cancer prevalence 24%). The base-case incremental cost-effectiveness ratio for T2-MRI was <£30,000 per QALY (all cohorts). Probabilistic sensitivity analysis showed high uncertainty surrounding the incremental cost-effectiveness of T2-MRI in moderate prevalence cohorts. The cost-effectiveness of MRS compared with T2-MRI and TRUS was sensitive to several key parameters. LIMITATIONS: Non-English-language studies were excluded. Few studies reported DCE-MRI/DW-MRI. The modelling was hampered by limited data on the relative diagnostic accuracy of alternative strategies, the natural history of cancer detected at repeat biopsy, and the impact of diagnosis and treatment on disease progression and health-related quality of life. CONCLUSIONS: MRS had higher sensitivity and specificity than T2-MRI. Relative cost-effectiveness of alternative strategies was sensitive to key parameters/assumptions. Under certain circumstances T2-MRI may be cost-effective compared with systematic TRUS. If MRS and DW-MRI can be shown to have high sensitivity for detecting moderate/high-risk cancer, while negating patients with no cancer/low-risk disease to undergo biopsy, their use could represent a cost-effective approach to diagnosis. However, owing to the relative paucity of reliable data, further studies are required. In particular, prospective studies are required in men with suspected PC and elevated PSA levels but previously negative biopsy comparing the utility of the individual and combined components of a multiparametric magnetic resonance (MR) approach (MRS, DCE-MRI and DW-MRI) with both a MR-guided/-directed biopsy session and an extended 14-core TRUS-guided biopsy scheme against a reference standard of histopathological assessment of biopsied tissue obtained via saturation biopsy, template biopsy or prostatectomy specimens. STUDY REGISTRATION: PROSPERO number CRD42011001376. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Comparison of laparoscopic adjustable gastric banding (LAGB) with other bariatric procedures; a systematic review of the randomised controlled trials.

BACKGROUND: Bariatric surgery can provide efficient weight loss and improvement in obesity-related co-morbidities in adults. Laparoscopic adjustable gastric banding (LAGB) comprised 30.3% of all bariatric procedures between 2009 and 2010 in the UK. This review evaluates the level 1 evidence for change in co-morbidities, quality of life (QoL) and weight provided by LAGB compared with other bariatric procedures. METHOD: Systematic literature search of MEDLINE, EMBASE and CENTRAL (1988 to May 2011) was performed. Only randomised controlled trials (RCTs) were included. Studies with non-surgical comparators, open gastric banding procedures or adolescent participants were excluded. Primary outcome was change in co-morbidities. Secondary outcomes included QoL, weight loss, complications, operation time and length of stay. RESULTS: Five RCTs met the inclusion criteria. Vertical banded gastroplasty, sleeve gastrectomy and gastric bypass were compared to LAGB. Co-morbidities were reported in two studies and QoL in one. LAGB was comparable to other procedures for both of these outcomes. All five trials showed LABG to be effective in weight loss, however all comparative procedures resulted in greater weight loss. Operative time and length of hospital stay were significantly shorter with LAGB. Short-term complications were found to be consistently lower in the LAGB group. Evidence was divided with respect to long-term complications. CONCLUSION: Co-morbidities and QoL are poorly reported and showed no difference between LAGB and other bariatric procedures. Evidence suggests that LAGB is not the most effective surgical procedure to reduce weight. LAGB is associated with lower early complications and shorter operative time and length of stay, and therefore may be preferable to patients.

Systematic review of intraoperative cholangiography in cholecystectomy.

BACKGROUND: Intraoperative cholangiography (IOC) is used to detect choledocholithiasis and identify or prevent bile duct injury. The aim of this study was systematically to review the randomized clinical trials of IOC for these two indications. METHODS: MEDLINE, Embase, the Cochrane Library, clinicaltrials.gov and the World Health Organization database of clinical trials were searched systematically (January 1980 to February 2011) to identify trials. Two authors performed the literature search and extracted data independently. Primary endpoints were bile duct injury and retained common bile duct (CBD) stones diagnosed at any stage after surgery. Preliminary meta-analysis was undertaken, but the trials were too methodologically heterogeneous and the outcome events too infrequent to allow meaningful meta-analysis. RESULTS: Eight randomized trials were identified including 1715 patients. Six trials assessed the value of routine IOC in patients at low risk of choledocholithiasis. Two trials randomized all patients (including those at high risk) to routine or selective IOC. Two cases of major bile duct injury were reported, and 13 of retained CBD stones. No trial demonstrated a benefit in detecting CBD stones. IOC added a mean of 16 min to the total operating time. CONCLUSION: There is no robust evidence to support or abandon the use of IOC to prevent retained CBD stones or bile duct injury. Level 1 evidence for IOC is of poor to moderate quality. None of the trials, alone or in combination, was sufficiently powered to demonstrate a benefit of IOC. Further small trials cannot be recommended.

Estrogenic effects of genistein on reproductive tissues of ovariectomized gilts.

The soybean phytoestrogen genistein has a range of estrogenic actions demonstrated in various species; however, only limited research has been done to investigate its effects in swine. The objective of this study was to characterize the effects of a graded dose of genistein on estrogen-sensitive uterine and cervical tissues in ovariectomized gilts. Thirty-four postpubertal gilts were ovariectomized and assigned randomly to 1 of 6 treatment groups 15 d postovariectomy. Treatment groups received vehicle, estradiol benzoate (2 mg/d), or genistein (50, 100, 200, or 400 mg/d) via intramuscular injection at 12-h intervals for 10 d. Following the treatment period, gilts were euthanized, and uterine and cervical tissues were collected and processed for chemical or histological analysis. Uterine and cervical tissue mass, as indicated by wet, dry, and protein weights and total DNA content (expressed per 100 kg of BW), increased as the dosage of genistein increased (P < 0.001 for each regression). Uterine and cervical wet weights were increased by a dosage of 200 mg of genistein/d (P < 0.001 and P < 0.01, respectively) but not by 100 mg of genistein/d (P = 0.38 and P = 0.14, respectively) compared with those of control gilts. Height of epithelial cells lining the uterine glands and the lumen of uterus and cervix increased when gilts were treated with estradiol benzoate or 400 mg of genistein/d (P < 0.01). When the gilts were treated with estradiol benzoate or 400 mg of genistein/d, immunohistochemical staining demonstrated an increase in the percentage of cells that stained positive for progesterone receptor in the uterine glands and in the cells lining the vaginal cervix (P < 0.05). In gilts treated with 400 mg of genistein/d, the percentage of cells stained positive for proliferating cell nuclear antigen increased in the epithelium of the uterine glands, uterine lumen, and vaginal cervix (P < 0.05). Tissue growth was stimulated by genistein in a dosage-dependent manner, although no dosage of genistein induced a response as great as that of estradiol benzoate. Estrogen-sensitive tissues of the ovariectomized gilt, such as the cervix and uterus, are affected by injection of large dosages of the phytoestrogen genistein. The sensitivity of the uterus of the gilt to estrogenic substances makes it a potential model to examine the impact of environmental endocrine modulators on reproductive tissues.

Quantification of mammary gland tissue size and composition changes after weaning in sows.

The objectives of this study were to characterize the tissue compositional changes in porcine mammary glands after weaning and to determine whether administration of estradiol alters the profile of these tissue changes. Forty-five primiparous sows were assigned randomly to one of two treatment groups after weaning, control or estrogen treated. Estrogen-treated sows received twice-daily injections of estradiol-17beta (0.125 mg/kg of BW); control sows received vehicle injections. Sows were weaned at d 21 of lactation and killed on either d 0 (d of weaning; n = 5) or on d 2, 3, 4, 5, or 7 after weaning (n = 4 per treatment on each day). Teat order relative to suckling behavior was observed on the day before weaning to determine which mammary glands the piglets suckled. Suckled and non-suckled glands were identified from the teat order observation, and individual mammary glands were collected at slaughter. Mammary glands were trimmed of skin and extraneous fat pad, individually weighed, and bisected to measure cross-sectional area. The remaining half of each gland was ground and stored at -20 degrees C for chemical analyses. Frozen tissue was used for measuring tissue DNA, DM, protein, fat, and ash contents. Suckled mammary glands of sows undergo significant and dramatic changes during the initial 7 d after weaning, with significant changes occurring even by d 2 after weaning. Mean cross-sectional area of parenchymal tissue in suckled mammary glands decreased from 59.7 +/- 2.1 cm2 on the day of weaning to 26.8 +/- 2.3 cm2 by d 7 after weaning (P < 0.0001). Mammary gland wet weight decreased from 485.9 +/- 22.0 g on the day of weaning to 151.5 +/- 24.8 g by d 7 after weaning (P < 0.0001), whereas DNA decreased from 838.8 +/- 46.2 g on the day of weaning to 278.4 +/- 52.5 g by d 7 after weaning (P < 0.0001). The changes in gland wet weight and DNA during the period of mammary gland involution in the sow represent loses of over two-thirds of the parenchymal mass and nearly two-thirds of the cells that were present on the day of weaning. Estrogen treatment did not affect overall mammary involution during the first 7 d after weaning. Mammary glands that were not suckled during lactation had no further loss of parenchymal tissue during the first 7 d after weaning. Mammary gland involution in the sow is a rapid process and is probably irreversible within 2 or 3 d after weaning.

Drinking patterns among Hispanic adolescents: results from a national household survey.

OBJECTIVE: This is one of the first studies to examine and compare alcohol use for adolescent Cubans, Mexican Americans, Puerto Ricans and other Hispanics. METHOD: The data come from the 1993 National Household Survey on Drug Abuse (NHSDA), a national probability sample of the U.S. household population. The sample examined here (N = 1,865, 52% male) comprises 200 Cubans, 1,133 Mexican Americans, 255 Puerto Ricans and 277 Central/South Americans who were 12 to 17 years old. Drinking patterns are measured using a quantity-frequency index, and analyses are conducted using Stata. RESULTS: In the cross-tabulations, no ethnic differences in drinking patterns are found for males or females, nor is there evidence of gender differences within ethnic groups, although there are some age differences in alcohol use. In the logistic regression analyses, two ethnic differences emerge, although the factors most consistently associated with drinking behaviors in these analyses are age, Spanish language use and urban residence. Additional analyses using the 1998 NHSDA suggest that ethnic differences in alcohol use may emerge in late adolescence/early adulthood. CONCLUSIONS: Given the established findings of ethnic and gender differences in drinking among adult Hispanics, it is surprising that few differences are evidenced in adolescence. Future research should explore whether such differences emerge during the transition into adulthood and, if so, identify factors that produce them. In addition, to increase understanding of these ethnic groups' drinking patterns, future research should further investigate the factors associated with Hispanic adolescents' alcohol use, including both consideration of whether the predictors are the same across groups and of the role of sociocultural factors.

Nutritionally directed compensatory growth enhances heifer development and lactation potential.

The objectives of this study were 1) to examine the interactive influence of a compensatory nutrition regimen and lasalocid supplementation on dairy heifer growth performance and 2) to document the extent to which compensatory growth sustains lactation potential over the first two lactation cycles. Twelve Holstein heifers, weighing an average of 160 kg (about 6 mo of age) were randomly assigned to treatments arranged in a 2 x 2 factorial design. Treatment variables were two dietary regimens (control and stair-step compensatory nutrition) and two levels of lasalocid (0 and 200 mg/d). The control heifers were fed a diet containing 12% crude protein (CP) and 2.35 Mcal of metabolizable energy (ME) per kilogram of dry matter. The stair-step compensatory nutrition heifers were subjected to a phased nutrition regimen and reared according to an alternating 3-2-4-3-4-2-mo schedule. The first stair-step (prepubertal phase) consisted of energy restriction [17% CP and 2.35 Mcal/kg of ME] for 3 mo followed by realimentation (12% CP and 3.05 Mcal/kg of ME) for 2 mo. The second step (puberty and breeding) consisted of energy restriction for 4 mo followed by realimentation for 3 mo. The third step (gestation period) was energy restriction for 4 mo concluding with realimentation for 2 mo. Dry matter intake of heifers during the restriction phase was limited to 70% of the control intake. Heifers were given ad libitum access to a high energy density diet during realimentation to allow compensatory development. Stair-step heifers supplemented with lasalocid had the highest efficiency of growth (body weight gain/dry matter intake), suggesting synergistic metabolism of lasalocid with compensatory growth action. Compensatory growth induced during the last trimester enhanced metabolic status by increasing circulating insulin and decreasing triglyceride levels. Heifers on the stair-step regimen had a significant increase in milk yield during the first (21%) and second (15%) lactation cycles. These results support our thesis that compensatory growth induced during an allometric growth phase improves mammary development and energy and protein metabolic status of dairy heifers.

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas.

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of 5-fluorouracil (250 mg/m2/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of 5-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 15 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy.

Under the influence: risky sexual behavior and substance abuse among driving under the influence offenders.

BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the associations between alcohol and drug abuse and risky sexual practice in a sample of 366 driving under the influence (DUI) offenders. STUDY DESIGN: Data were collected from a sample of participants at a university-operated drunk driving intervention program. Specific indicators included established or severe alcohol/drug use problems, multiple drugs used, multiple alcohol/drug related arrests, and early regular alcohol use. Multiple sexual partners, condom use, and having sex while under the influence of alcohol or drugs were used to measure risky sexual behavior patterns. Correlation and logistic regression analyses examined associations between these substance abuse and sexual risk taking measures. RESULTS: Substance abuse in general was unrelated to risky sexual behavior such as multiple sexual partners or lack of condom use. However, having sex while high from alcohol or drugs was significantly associated with substance abuse. Moreover, having sex while high was significantly related to both risky sex and a history of sexually transmitted disease. CONCLUSIONS: Having sex while high may be an important behavior to address to prevent STDs in the DUI population. Assessing relationships between substance abuse and risky sexual behavior poses a challenge to researchers because any estimates about this association may be dependent on the measure of sexual behavior that is used. An integrated intervention approach that addresses both substance abuse prevention and safe sexual practice appears crucial and effective for educating "risk takers" such as DUI offenders. However, these data caution that for those who are dependent upon alcohol and/or other drugs, education solely emphasizing risk reduction procedures is likely to be inefficient until their chemical dependency is addressed.

Illicit drug use by women with disabilities.

As in the general female population, women with disabilities face a number of situations that encourage illicit drug use, such as low self-esteem, peer pressure, and family history of substance abuse. In addition, women with disabilities more frequently encounter problems of personal adjustment, unusual developmental experiences, easy access to prescription drugs, unemployment, and medical or health-related difficulties. Using a random sample of 900 women with disabilities, we conducted a study of the patterns of illicit drug use and risk factors relating to illicit drug use among women with various disabilities. Multiple regression analyses revealed that age, illicit drug use by a best friend, being a victim of substance-abuse-related violence, and attitudes toward substance use by people with disabilities were significantly related to illicit drug use by the study population. The implications of these findings are discussed.

Late acute rejection occurring in liver allograft recipients.

To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR) in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1). Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2). LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant). Mean trough CsA levels were lower in patients with LAR compared with those without (224 +/- 66 ng/mL versus 233 +/- 49 ng/mL) but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5 +/- 1.6 mg/day versus 6.5 +/- 2.9 mg/day, P = 0.007) and CsA nadir values (129 +/- 60 ng/mL versus 186 +/- 40 ng/mL, P = 0.03) were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83%) of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8%) receiving prednisone 5 mg/day or more (P = 0.004). In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

Arsenic speciation by ion-exchange separation and graphite-furnace atomic-absorption spectrophotometry.

As(III), As(V), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) were determined by graphite-furnace atomic-absorption spectrophotometry after separation of the species by ion-exchange chromatography. The detection limits (ng/ml) were DMA 0.02, MMA 2.0, As(V) 0.4 and total arsenic 4.0. As(III) was determined by difference. This system gave better detection limits and/or shorter analysis times than previously reported systems.