Publications

CONTEXT

Counseling smokers to quit smoking and providing them with pharmaceutical cessation aides are among the most beneficial and cost-effective interventions that clinicians can offer patients. Yet assistance with quitting is not universally covered by health plans or offered by all clinicians. Analysis of stakeholders' perspectives and interests can identify the barriers to more widespread provision of cessation services and suggest strategies for the public policy agenda to advance smoking cessation.

METHODS

Review of literature and discussions with representatives of stakeholders.

FINDINGS

All stakeholders-health plans, employers, clinicians, smokers, and the government-face barriers to broader smoking cessation activities. These range from health plans' perceiving that covering counseling and pharmacotherapy will increase costs without producing commensurate health care savings, to clinicians' feeling unprepared and uncompensated for counseling. Like other preventive measures aimed at behavior, efforts directed at smoking cessation have marginal status among health care interventions. State governments can help correct this status by increasing Medicaid coverage of treatment and expanding coverage for state employees. The federal government can promote the adoption of six initiatives recommended by a government subcommittee on cessation: set up a national quit line, develop a media campaign to encourage cessation, include cessation benefits in all federally funded insurance plans, create a research infrastructure to improve cessation rates, develop a clinician training agenda, and create a fund to increase cessation activities through a new $2 per pack cigarette excise tax. Both the federal and state governments can increase cessation by adopting policies such as the higher cigarette tax and laws prohibiting smoking in workplaces and public places.

CONCLUSIONS

Public policy efforts should assume greater social responsibility for smoking cessation, including more aggressive leadership at the state and federal levels, as well as through advocacy, public health, and clinician organizations.

Malaria case management in Africa is characterized by presumptive treatment and substantial overtreatment. We evaluated an integrated team-based training program on malaria case management. Surveillance data 120 days before and after training were compared at eight health facilities in Uganda. After training, the proportion of patients with suspected malaria referred for blood smears increased from 38.3% to 54.6% (P=0.04) in persons<5 years of age years and from 34.1% to 53.4% (P=0.02) in those>or=5 years of age. The proportion of patients with negative blood smears prescribed antimalarial drugs decreased from 47.9% to 19.6% (P<0.001) in persons<5 years of age and from 38.8% to 15.6% (P<0.001) in those>or=5 years of age. Training did not improve the proportion of patients with positive blood smears prescribed antimalarial drugs, the proportion of patients prescribed appropriate antimalarial drugs, or the diagnostic accuracy of microscopy. Integrated team-based training may improve malaria case management and reduce the number of unnecessary antimalarial treatments.

We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.

A survey-based COPD severity scoring algorithm could prove useful for targeted disease management and risk-adjustment. For this purpose, we sought to prospectively validate a COPD severity score that had previously been cross-sectionally validated. Using a population-based sample of 267 adults with self-reported physician-diagnosed COPD, we examined the extent to which this COPD severity score predicts future respiratory hospitalizations, emergency department (ED) visits, and outpatient visits. Structured telephone interviews, conducted at baseline and on an annual basis in two subsequent years, determined COPD severity scores and health-care utilization. A basic predictive model for respiratory-specific health-care utilization was developed using sociodemographics, tobacco history, and medical comorbidity data in multivariate logistic regression analysis. The added predictive value of the COPD severity score over and above this basic model was then evaluated by testing the change in model concordance indices. Our analysis demonstrated that the COPD severity score did, in fact, increase the concordance-index of models predicting future respiratory hospitalizations (increase from 80% to 87%; P = 0.03), ED visits (64% to 82%, P = 0.003), and outpatient visits (59% to 77%, P < 0.0001). In a separate analysis, both a greater baseline severity score and worsening of the severity score over time were prospectively associated with each outcome studied (P < 0.05 for each). In conclusion, the COPD severity score adds predictive value in estimating future respiratory-specific health-care utilization and is longitudinally responsive to evolving changes in COPD status over time. This severity score may be used to adjust for disease severity or to identify high-risk populations.

Observations on the association between exposure to common outdoor air pollutants and allergic sensitization have not been consistent. Little research has been done on the effects of prenatal exposure or the effect among asthmatics. The association between prenatal and early-life exposures and outdoor air pollutants with allergic sensitization was examined within a cohort of 170 children ages 6-11 years with asthma, living in the Central Valley of California. Allergic sensitization was ascertained by skin-prick tests to 14 allergens. Prenatal and early-life exposure to ozone (O(3)), nitrogen dioxide (NO(2)), carbon monoxide (CO) and particulate matter with a median aerodynamic diameter < 10 micro m (PM(10)) was reconstructed for each child. Models were developed for sensitized to (a) any allergen, (b) at least one outdoor allergen, and (c) at least one indoor allergen. In multivariable analyses, higher exposure to CO during pregnancy was associated with an increased risk of sensitization to at least one outdoor allergen. The largest effect was seen for the association between exposure to 8-hour daily maximum CO during pregnancy and sensitization to at least one outdoor allergen. (OR = 1.55 (95% CI: 1.01, 2.37)) per interquartile range (IQR) increase.) Similar effects estimates were seen for 2nd trimester exposure to CO, but these were less precisely estimated (OR = 1.45 (95%CI: 0.90, 2.35)). No significant associations with the pollutants were seen for sensitization to allergens in general or to at least one indoor allergen. Exposure to traffic-related pollutants during pregnancy may increase the risk of sensitization to outdoor allergens among asthmatic children.

Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. In this study, we defined the HIV epitopes targeted by 76 pediatric subjects (47 HIV infected and 29 HIV exposed, but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFN-gamma, TNF-alpha, and IL-2. No responses were detected among HIV-uninfected infants, whereas responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 mo old (p = 0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (log viral load 5.8 vs 5.0; p = 0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 mo of age, and that HIV-specific CD4 cell responses were of universally low frequency among antiretroviral-naive children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV.

U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 ancestry informative markers in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco Bay area and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (95% CI) for ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European ancestry was associated with increased breast cancer risk. The OR for a 25% increase in European ancestry was 1.79 (95% CI, 1.28-2.79; P<0.001). When known risk factors and place of birth were adjusted for, the association with European ancestry was attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06-2.11; P=0.013). Further work is needed to determine if the association is due to genetic differences between populations or possibly due to environmental factors not measured.

BACKGROUND

As people live longer, there is increasing potential for mental disorders to interfere with testamentary distribution and render older people more vulnerable to "undue influence" when they are making a will. Accordingly, clinicians dealing with the mental disorders of older people will be called upon increasingly to advise the courts about a person's vulnerability to undue influence.

METHOD

A Subcommittee of the IPA Task Force on Testamentary Capacity and Undue Influence undertook to establish consensus on the definition of undue influence and the provision of guidelines for expert assessment of risk factors for undue influence.

RESULTS

International jurisdictions differ in their approach to the notion of undue influence. Despite differences in legal systems, from a clinical perspective, the subcommittee identified some common "red flags" which might alert the expert to risk of undue influence. These include: (i) social or environmental risk factors such as dependency, isolation, family conflict and recent bereavement; (ii) psychological and physical risk factors such as physical disability, deathbed wills, sexual bargaining, personality disorders, substance abuse and mental disorders including dementia, delirium, mood and paranoid disorders; and (iii) legal risk factors such as unnatural provisions in a will, or provisions not in keeping with previous wishes of the person making the will, and the instigation or procurement of a will by a beneficiary.

CONCLUSION

This review provides some guidance for experts who are requested by the courts to provide an opinion on the risk of undue influence. Whilst international jurisdictions require different thresholds of proof for a finding of undue influence, there is good international consensus on the clinical indicators for the concept.