Racial/ethnic differences in life-course heavy drinking from adolescence to midlife.

Information on heavy drinking over the life course might help to explain racial/ethnic disparities in alcohol-related problems, morbidity, and mortality. Using data from the 2009-2010 U.S. National Alcohol Survey (n = 3,026), we analyzed retrospective decades-based measures of heavy drinking during respondents' teens, 20s, 30s, and 40s. Results indicate that Latino men and African American women have greater risk for persistent-high (vs. declining) heavy-drinking trajectories than Caucasian men and women, and that socioeconomic disadvantage partly accounts for this disparity in women. Prospective longitudinal studies are needed to confirm these results and to elucidate the relationship of life-course heavy-drinking patterns with health-related outcomes, and disparities in these.

Statewide Policy Change in Pediatric Dental Care, and the Impact on Pediatric Dental and Physician Visits.

Introduction In 2007, the California signed legislation mandating a dental visit for all children entering kindergarten or first grade; no such mandate was made for physician visits. This study examines the impact of this policy change on the risk factors associated with obtaining pediatric dental and physician health care visits. Methods Every 2 years, California Health Interview Survey conducts a statewide survey on a representative community sample. This cross-sectional study took advantage of these data to conduct a "natural experiment" assessing the impact of this policy change on both pediatric physician and dental care visits in the past year. Samples included surveys of adults and children (ages 5-11) on years 2005 (n = 5096), 2007 (n = 4324) and 2009 (n = 4100). Results Although few changes in risk factors were noted in pediatric physician visits, a gradual decrease in risk factors was found in pediatric dental visits from 2005 to 2009. Report of no dental visit was less likely for: younger children (OR -0.81, CI 0.75-0.88), insured children (OR 0.34, CI 0.22-0.53), and children who had a physician's visit last year (OR 0.37, CI 0.25-0.53) in 2005. By 2007, absence of insurance was the only risk factor related to having no dental visit (OR 0.34, CI 0.19-0.61). By 2009, no a priori measured risk factors were associated with not having a dental visit for children aged 5-11 years. Conclusions A statewide policy mandating pediatric dental visits appears to have reduced disparities. A policy for medical care may contribute to similar benefits.

Stability of ranibizumab during continuous delivery from the Port Delivery Platform.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system that has the potential to reduce treatment burden in patients with retinovascular diseases. The Port Delivery Platform (PD-P) implant is a permanent, indwelling device that can be refilled in situ through a self-sealing septum and is designed to continuously deliver ranibizumab by passive diffusion through a porous titanium release control element. We present results for the studies carried out to characterize the stability of ranibizumab for use with the PD-P. Simulated administration, in vitro release studies, and modeling studies were performed to evaluate the compatibility of ranibizumab with the PD-P administration components, and degradation and photostability in the implant. Simulated administration studies demonstrated that ranibizumab was highly compatible with the PD-P administration components (initial fill and refill needles) and commercially available administration components (syringe, transfer needle, syringe closure). Subsequent simulated in vitro release studies examining continuous delivery for up to 12 months in phosphate buffered saline, a surrogate for human vitreous, showed that the primary degradation products of ranibizumab were acidic variants. The presence of these variants increased over time and potency remained high. The stability attributes of ranibizumab were consistent across multiple implant refill-exchanges. Despite some degradation within the implant, the absolute mass of variants released daily from the implant was low due to the continuous release mechanism of the implant. Simulated light exposure within the implant resulted in small increases in the relative amount of ranibizumab degradants compared with those seen over 6 months.

Life course outcomes on mental and physical health: the impact of foster care on adulthood.

OBJECTIVE: We compared the prevalence rates of mental health and physical health problems between adults with histories of childhood foster care and those without. METHODS: We used 2003-2005 California Health Interview Survey data (n = 70,456) to test our hypothesis that adults with childhood histories of foster care will report higher rates of mental and physical health concerns, including those that affect the ability to work, than will those without. RESULTS: Adults with a history of childhood foster care had more than twice the odds of receiving Social Security Disability Insurance because they were unable to work owing to mental or physical health problems for the past year, even after stratifying by age and adjusting for demographic and socioeconomic characteristics. CONCLUSIONS: Childhood foster care may be a sentinel event, signaling the increased risk of adulthood mental and physical health problems. A mental and physical health care delivery program that includes screening and treatment and ensures follow-up for children and youths who have had contact with the foster care system may decrease these individuals' disproportionately high prevalence of poor outcomes throughout their adulthood.

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.

Faecal occult blood screening: knowledge, attitudes, and practice in four Hong Kong primary care clinics.

OBJECTIVES. To assess primary care patients for their awareness, knowledge, and attitude towards colorectal cancer and screening, to report on the uptake of faecal occult blood test screening and the results of screening, and explore predictors of screening uptake. DESIGN. Cross-sectional study. SETTING. Four primary care clinics in Hong Kong. PATIENTS. A total of 1664 patients aged 50 to 74 years attending the clinics in the period July 2006 to July 2007. MAIN OUTCOME MEASURES. Percentage of subjects who were aware that colorectal cancer is common and curable at an early stage, and who knew that faecal occult blood test or colonoscopy is useful for screening; relevant knowledge score; uptake rate of faecal occult blood testing; rate of testing positive; and factors predicting uptake. RESULTS. A total of 1645 questionnaires were collected. In all, 89% (95% confidence interval, 88-91%) were aware that colorectal cancer is common, 95% (94-96%) believed faecal occult blood test and colonoscopy are useful for screening, and 58% (56-61%) achieved a knowledge score of 50% or above. The uptake rate of the faecal occult blood test was 35%. Uptake was higher among those with a positive family history (odds ratio=1.57; 95% confidence interval, 1.08-2.27; P=0.02), those who were more aware that colorectal cancer is common (1.86; 1.29-2.69; P=0.001), and that colorectal cancer is potentially curable at an early stage (1.76; 1.32-2.36; P=0.0001). Rate of testing positive was 2.1% (95% confidence interval, 0.9-3.3%); no colorectal cancer was detected and the neoplasia detection rate (for cancers and adenomas) was 5.1 per 1000 subjects screened. CONCLUSIONS. Patients were aware that colorectal cancer is common in our community, and faecal occult blood test or colonoscopy is useful for screening. The uptake of screening was low, though relatively higher for those with a positive family history and greater awareness of the high frequency and potential for cure of colorectal cancer. Faecal occult blood test positivity rate was 2.1%, and neoplasia detection rate 5.1 per 1000 screened.

End-of-Study Results for the Ladder Phase 2 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, randomized, active treatment-controlled phase 2 clinical trial. PARTICIPANTS: Patients diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (N = 220). METHODS: Patients were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections. MAIN OUTCOME MEASURES: End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. RESULTS: At study end, the mean time on study was 22.1 months (range, 10.8-37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients went 12 months or longer without meeting refill criteria in the PDS 10-mg/ml, 40-mg/ml, and 100-mg/ml treatment arms, respectively. At month 22, the observed mean BCVA change from baseline was ‒4.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒2.3 ETDRS letters, +2.9 ETDRS letters, and +2.7 ETDRS letters in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg treatment arms, respectively. At month 22, the observed mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg treatment arms. No new safety signals were detected during the additional follow-up. CONCLUSIONS: Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.

Concurrent and simultaneous drug and alcohol use: results of the 2000 National Alcohol Survey.

This study estimates the prevalence, assesses predictors and evaluates factors associated with concurrent and simultaneous use of drugs and alcohol in the United States population. Using data from the 2000 National Alcohol Survey (n=7612), respondents were asked if they used specific drugs in the last 12 months. Current drinkers who reported using each type of drug were asked if they used alcohol and the drug at the same time. Approximately 10% reported using marijuana in the last 12 months (concurrent use); 7% reported drinking alcohol and using marijuana at the same time (simultaneous use). Approximately 5% of current drinkers reported using drugs other than marijuana in the last 12 months; 1.7% reported drinking alcohol and using drugs other than marijuana at the same time. Being younger, having less than a high school education, not having a regular partner and having heavier drinking patterns were associated with using alcohol and marijuana simultaneously. Simultaneous use of marijuana and alcohol as well as other drugs and alcohol were significantly related to social consequences, alcohol dependence, and depression. These results mirror clinical populations in which increasingly younger clients report use of alcohol and drugs and need treatment for both.

Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells.

PDZD2 (PDZ domain containing 2) is a multi-PDZ protein expressed in pancreas and many other tissues. PDZD2 shows extensive homology to pro-interleukin-16 (pro-IL-16) and is localized mainly to the endoplasmic reticulum. We have recently demonstrated that PDZD2, like pro-IL-16, is proteolytically cleaved at its C-terminus to generate a secreted protein, sPDZD2 (for secreted PDZD2). To understand the possible functional role of PDZD2 in pancreas, we investigated the cellular distribution of PDZD2 in adult pancreas using an antiserum that recognizes both the full-length and secreted forms of PDZD2. Immunohistochemical analysis revealed a strong expression of PDZD2 in pancreatic islet beta cells but not alpha cells. Consistent with the beta-cell-enriched expression of PDZD2, immunoblot analysis indicated expression of both full-length PDZD2 and sPDZD2 in the insulinoma cell line INS-1E. A recombinant sPDZD2 protein was synthesized for study of its functional effect on INS-1E cells. In culture media with limiting serum, co-incubation with sPDZD2 stimulated the proliferation of INS-1E cells. The mitogenic effect of sPDZD2 was concentration-dependent, and was associated with a slight inhibition of the insulin promoter activity at high sPDZD2 concentrations. As a potential mitogen of beta-like cells, sPDZD2 may be useful for the optimization of beta-cell growth and differentiation in vitro.

Who goes to alcohol and drug treatment? Understanding utilization within the context of insurance.

OBJECTIVE: This study assesses the differential roles of demographic characteristics, problem severity, motivational factors and insurance in entrance into alcohol and drug treatment. METHOD: A probability sample of adult problem and dependent drinkers from a Northem California county (N = 672) and consecutive adult intakes from the county's public (n = 298) and private (n = 628) alcohol and drug treatment programs. Interviewers conducted telephone screening for individuals meeting problem-drinking criteria in the general population; in-person interviews were conducted for those who screened positive, and also for individuals entering treatment. RESULTS: Insurance did not play an independent role in treatment entry. In logistic regression analysis, using a model from the medical utilization literature, black ethnicity (odds ratio [OR] = 2.98, p < .001); older age (OR = 4.67, p < .001); less education (OR = 1.81, p < .01); legal (OR = 7.46, p < .001) and work (OR = 3.57,p <.001) pressures; higher psychiatric (OR = 4.03,p <.001) and drug (OR = 3.04,p <.001) severity; and social consequences (OR = 1.35, p < .01) predicted treatment entry. Interventions from legal sources (OR = 6.22, p < .01) were related to entering treatment for the uninsured; legal (OR = 7.02, p < .001), workplace (OR = 6.01, p < .001) and family (OR = 1.62, p < .05) pressures were related for the insured. CONCLUSIONS: Social consequences, rather than severity of dependence, in both insured and uninsured problem drinkers are important predictors of treatment entry when traditional utilization measures are controlled. Public programs play a crucial part in the alcohol and drug treatment system, and their viability is important as health policy changes.

Adverse childhood events, substance abuse, and measures of affiliation.

Adverse childhood events may influence later behaviors, including adulthood substance use and social affiliation. Studies have noted high prevalence rates of adverse childhood experiences and adulthood substance abuse among homeless adults. Using an existing longitudinal, countywide probability sample of 397 homeless adults, we examine the relationships among adverse childhood events on adulthood substance use, and the relationship of these variables to affiliation. Almost 75% of the sample had experienced an adverse childhood event. Path analysis indicated adulthood substance abuse mediated the inverse relationship between adverse childhood events and two measures of adulthood affiliation. Thus, although there is a relationship between adverse childhood events and adulthood substance use, it is adulthood substance use that determines most aspects of affiliation.

Substance use and separation of homeless mothers from their children.

OBJECTIVES: This study examined whether homeless mothers with substance use problems were more likely to experience separations from their children and whether recent substance use had an impact on the family's ability to receive public entitlement income consistently over the 15-month study period. METHODS: This study used an existing longitudinal data set consisting of a county-wide probability sample of 104 homeless women who had children under 18 years old. RESULTS: Only 29.1% of women had all their children with them throughout the 15-month study period. Mothers who had been separated from their children were more likely to have a current substance use disorder and to have been homeless for at least a year compared to other homeless mothers. CONCLUSIONS: Because many women with recent substance use had already had lost custody of their children, substance use contributed to loss of child custody among mothers who did not have substance use disorders.

Applicability of Type A/B alcohol dependence in the general population.

BACKGROUND: This study examined the concurrent and predictive validity of Type A/B alcohol dependence in the general population-a typology developed in clinical populations to gauge severity of dependence. METHODS: Data were drawn from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The sample included 1,172 alcohol-dependent drinkers at baseline who were reinterviewed three years later. Latent class analysis was used to derive Type A/B classification using variables replicating the original Type A/B typology. Predictive validity of the Type A/B classification was assessed by multivariable linear and logistic regressions. RESULTS: A two-class solution consistent with Babor's original Type A/B typology adequately fit the data. Type B alcoholics in the general population, compared to Type As, had higher alcohol severity and more co-occurring drug, mental, and physical health problems. In the absence of treatment services utilization, Type B drinkers had two times the odds of being alcohol dependent three years later. Among those who utilized alcohol treatment services, Type B membership was predictive of heavy drinking and drug dependence, but not alcohol dependence, three years later. CONCLUSIONS: Findings suggest that Type A/B classification is both generalizable to, and valid within, the US general population of alcohol dependent drinkers. Results highlight the value of treatment for mitigating the persistence of dependence among Type B alcoholics in the general population. Screening for markers of vulnerability to Type B dependence could be of clinical value for health care providers to determine appropriate intervention.

Disparities in the use and quality of alcohol treatment services and some proposed solutions to narrow the gap.

OBJECTIVES: This study assessed racial-ethnic disparities in access to high-quality treatment for at-risk drinking and alcohol abuse in the United States and simulated strategies to narrow the gap. METHODS: Longitudinal data collected in 2001-2002 and 2004-2005 from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed to examine racial-ethnic disparities in receipt of alcohol interventions that were provided in primary care and specialty treatment settings and that met published clinical guidelines. The sample consisted of 9,116 respondents who met criteria for at-risk drinking or alcohol abuse in 2001-2002. Simulation analyses projected how disparities in treatment services utilization might change if clinical guidelines promoted access to care in more varied health and human service settings. RESULTS: Compared with whites, members of racial-ethnic minority groups had less than two-thirds the odds of receiving an alcohol intervention over the roughly four-year study period (odds ratio [OR]=.62, p<.05). This disparity increased after adjustment for socioeconomic confounders and frequency of heavy drinking (adjusted OR=.47, p=.003). The most pronounced disparities were between whites and U.S.-born and foreign-born Hispanics. Simulation analyses suggested that these disparities could be partially mitigated by extending care into nonmedical service venues. CONCLUSIONS: Current efforts to extend evidence-based alcohol interventions into medical settings address an important need but are likely to increase racial-ethnic disparities in access to high-quality treatment. Partial solutions may be found in expanding the range and quality of alcohol-related services provided in alternative delivery sites, including faith-based and social service institutions.

Common needs but divergent interventions for U.S. homeless and foster care children: results from a systematic review.

Many children living in homeless situations in the U.S. have temporary stays in foster care, and both populations suffer disproportionately higher rates of physical, psychological and social difficulties compared with other children. However, very little is known about which specific interventions achieve the best outcomes for children in these overlapping transitional living situations. To address this gap, we review existing literature to identify the most promising practices for children living in transition. A standardised vocabulary specific to each of three electronic databases (i.e. Medline, PsychINFO and CINAHL) was employed to identify studies that described an intervention specifically targeting foster care or homeless children and families. Separate systematic searches were conducted for homeless and foster children, and only studies published in English between January 1993 and February 2009 were selected. The final sample (n = 43) of articles described interventions that fell into two categories: mental health (n = 17) and case management (n = 26). No article included a sample containing both homeless and foster care children, and most studies on homeless children used case management interventions while most studies on foster care children focused on mental health interventions. Few articles employed rigorous study designs. Although repeatedly studies have demonstrated the overlap between populations of homeless and foster care children, studies focused on one population or the other. Virtually all studies on both homeless and foster children devised interventions to reduce trauma and family instability; yet, no evidence-based practice addresses the overlapping needs and potentially relevant evidence-based practice for these two populations. An important and vital next step is to establish an effective evidence-based intervention that reduces the impact of trauma on both U.S. populations of children living in transition.

Sources of biased inference in alcohol and drug services research: an instrumental variable approach.

OBJECTIVE: This study examined the potential for biased inference due to endogeneity when using standard approaches for modeling the utilization of alcohol and drug treatment. METHOD: Results from standard regression analysis were compared with those that controlled for endogeneity using instrumental variables estimation. Comparable models predicted the likelihood of receiving alcohol treatment based on the widely used Aday and Andersen medical care-seeking model. Data were from the National Epidemiologic Survey on Alcohol and Related Conditions and included a representative sample of adults in households and group quarters throughout the contiguous United States. RESULTS: Findings suggested that standard approaches for modeling treatment utilization are prone to bias because of uncontrolled reverse causation and omitted variables. Compared with instrumental variables estimation, standard regression analyses produced downwardly biased estimates of the impact of alcohol problem severity on the likelihood of receiving care. CONCLUSIONS: Standard approaches for modeling service utilization are prone to underestimating the true effects of problem severity on service use. Biased inference could lead to inaccurate policy recommendations, for example, by suggesting that people with milder forms of substance use disorder are more likely to receive care than is actually the case.

Toward a better understanding of when to apply propensity scoring: a comparison with conventional regression in ethnic disparities research.

PURPOSE: Despite growing popularity of propensity score (PS) methods used in ethnic disparities studies, many researchers lack clear understanding of when to use PS in place of conventional regression models. One such scenario is presented here: When the relationship between ethnicity and primary care utilization is confounded with and modified by socioeconomic status. Here, standard regression fails to produce an overall disparity estimate, whereas PS methods can through the choice of a reference sample (RS) to which the effect estimate is generalized. METHODS: Using data from the National Alcohol Surveys, ethnic disparities between White and Hispanics in access to primary care were estimated using PS methods (PS stratification and weighting), standard logistic regression, and the marginal effects from logistic regression models incorporating effect modification. RESULTS: Whites, Hispanics, and combined White/Hispanic samples were used separately as the RS. Two strategies utilizing PS generated disparities estimates different from those from standard logistic regression, but similar to marginal odd ratios from logistic regression with ethnicity by covariate interactions included in the model. CONCLUSIONS: When effect modification is present, PS estimates are comparable with marginal estimates from regression models incorporating effect modification. The estimation process requires a priori hypotheses to guide selection of the RS.

Long-term and chronic homelessness in homeless women and women with children.

The Chronic Homelessness initiative has directed millions of federal dollars to services for single "unaccompanied homeless" individuals, specifically excluding women living with their children. Using a data set with a nationally representative sample of homeless adults, we calculated the prevalence rates and profiles of long-term homelessness in homeless women (n = 849). With the exception of the criterion of being a single "unaccompanied individual," many women, including women with children, met the criteria for chronic homelessness including having a disability of mental health or substance abuse problems. Our findings suggest that the federal definition of chronic homelessness needs to be revised.

Do Alcohol Warning Labels Influence Men's and Women's Attempts to Deter Others from Driving When Intoxicated?

Research on the federally mandated alcohol warning label has found mixed results, but some findings are consistent with a modest influence on precautionary behaviors to reduce drinkers' self-reported drunk driving. We hypothesized that warnings would also influence the likelihood of intervening to deter other's driving after drinking. Using data from 1376 adult drinkers in a US national survey, a conceptual model reflecting effects of exposure to the label's drunk driving message on taking actions to avert another's driving under the influence was tested in a structural equation modeling framework. For males and females, in structural models with drinking and handling of alcoholic beverages potentially affecting both message recall and intervening, the predicted relationships were found between message recall and actions to deter another's drinking driving. This finding suggests that an important preventive effect of the alcohol warning label may be to legitimate collateral's attempts to avert another's drunk driving.