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Benowitz N.L.,San Francisco General Hospital | Benowitz N.L.,University of California at San Francisco
New England Journal of Medicine | Year: 2010

This review gives an account of the cigarette as a highly efficient nicotine delivery system. It explains how nicotine induces pleasure, reduces stress and anxiety, and causes addiction to tobacco smoking. The basis of nicotine addiction rests on its effects on the brain, but addiction is also influenced by learned or conditioned factors, genetics, and social and environmental conditions. Copyright © 2010 Massachusetts Medical Society. All rights reserved.


Deeks S.G.,San Francisco General Hospital
Annual Review of Medicine | Year: 2011

Although antiretroviral therapy for HIV infection prevents AIDS-related complications and prolongs life, it does not fully restore health. Long-term treated patients remain at higher than expected risk for a number of complications typically associated with aging, including cardiovascular disease, cancer, osteoporosis, and other end-organ diseases. The potential effect of HIV on health is perhaps most clearly exhibited by a number of immunologic abnormalities that persist despite effective suppression of HIV replication. These changes are consistent with some of the changes to the adaptive immune system that are seen in the very old ("immunosenescence") and that are likely related in part to persistent inflammation. HIV-associated inflammation and immunosenescence have been implicated as causally related to the premature onset of other end-organ diseases. Novel therapeutic strategies aimed at preventing or reversing these immunologic defects may be necessary if HIV-infected patients are to achieve normal life span. © 2011 by Annual Reviews. All rights reserved.


Luce J.M.,San Francisco General Hospital
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Increasingly in the United States and other countries, medical decisions, including those at the end of life, are made using a shared decision-making model. Under this model, physicians and other clinicians help patients clarify their values and reach consensus about treatment courses consistent with them. Because most critically ill patients are decisionally impaired, family members and other surrogates must make end-of-life decisions for them, ideally in accord with a substituted judgment standard. Physicians generally make decisions for patients who lack families or other surrogates and have no advance directives, based on a best interests standard and occasionally in consultation with other physicians or with review by a hospital ethics committee. End-of-life decisions for patients with surrogates usually are made at family conferences, the functioning of which can be improved by several methods that have been demonstrated to improve communications. Facilitative ethics consultations can be helpful in resolving conflicts when physicians and families disagree in end-of-life decisions. Ethics committees actually are allowed to make such decisions in one state when disagreements cannot be resolved otherwise.


Graf J.,San Francisco General Hospital
Current Opinion in Rheumatology | Year: 2013

Purpose of Review: Cocaine use is associated with several rheumatic syndromes. This review summarizes these clinical manifestations and highlights recent developments linked to levamisole-adulterated cocaine. Recent Findings: Cocaine use has been linked to several distinctive syndromes that can be difficult to distinguish from idiopathic rheumatic diseases. These disorders can range in severity from purely cosmetic damage to organ and/or life-threatening disease that includes sinonasal destruction and vasculitis. Many of these illnesses are associated with antineutrophil cytoplasmic antibodies (cytoplasmic, perinuclear and atypical perinuclear patterns). With the recent introduction of levamisole as a cocaine adulterant, a newly reported syndrome has emerged that is associated with neutropenia, retiform purpura with cutaneous necrosis and autoantibodies consisting of high-titre perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) with specificities for â€̃ atypical' antigens. Summary: Cocaine use is associated with clinical syndromes that closely mimic other primary rheumatic diseases. Given the high prevalence of cocaine use and its adulteration with levamisole, clinicians should be familiar with these rheumatic manifestations in order to avoid misdiagnosis and unnecessary treatment with potentially toxic therapies. Copyright © 2012 Lippincott Williams & Wilkins.


Luce J.M.,San Francisco General Hospital
Critical Care Medicine | Year: 2010

Objectives: To present a case of conflict over end-of-life care in the intensive care unit (ICU) and to describe how such conflicts have been resolved in the United States since the inception of ICUs. Data Sources: A nonsystematically derived sample of published studies and professional and lay commentaries on end-of-life care, ethical principles, medical decision-making, medical futility, and especially conflict resolution in the ICU. Study Selection: Some of those studies and commentaries dealing specifically with conflicts over end-of-life care in the ICU and their resolution. Data Synthesis: An historical review of conflict resolution over end-of-life issues in U.S. ICUs. Results and Conclusions: Conflict at the end of life in ICUs in the United States is relatively rare because most families and physicians agree about how patients should be treated. Nevertheless, conflict still exists over some patients whose families insist on care that physicians consider inappropriate and hence inadvisable, and over other patients whose families object to care that physicians prefer to provide. When such conflict occurs, mediation between families and physicians is usually successful in resolving it. Consultation from ethics committees also may be helpful in achieving resolution, and one state actually allows such committees to adjudicate disputes. Physicians who act unilaterally against family wishes run the risk of malpractice suits, although such suits usually are unsuccessful because the physicians are not shown to have violated standards of care. © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Although clinic-based cohorts are most representative of the "real world," they are susceptible to loss to follow-up. Strategies for managing the impact of loss to follow-up are therefore needed to maximize the value of studies conducted in these cohorts. The authors evaluated adult patients starting antiretroviral therapy at an HIV/AIDS clinic in Uganda, where 29% of patients were lost to follow-up after 2 years (January 1, 2004-September 30, 2007). Unweighted, inverse probability of censoring weighted (IPCW), and sampling-based approaches (using supplemental data from a sample of lost patients subsequently tracked in the community) were used to identify the predictive value of sex on mortality. Directed acyclic graphs (DAGs) were used to explore the structural basis for bias in each approach. Among 3,628 patients, unweighted and IPCW analyses found men to have higher mortality than women, whereas the sampling-based approach did not. DAGs encoding knowledge about the data-generating process, including the fact that death is a cause of being classified as lost to follow-up in this setting, revealed "collider" bias in the unweighted and IPCW approaches. In a clinic-based cohort in Africa, unweighted and IPCW approaches-which rely on the "missing at random" assumption-yielded biased estimates. A sampling-based approach can in general strengthen epidemiologic analyses conducted in many clinic-based cohorts, including those examining other diseases. American Journal of Epidemiology © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.


The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown. To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects. WE PROSPECTIVELY ENROLLED CONSECUTIVE, HOSPITALIZED, UGANDAN TB SUSPECTS IN TWO PHASES: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase. 477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0 [IQR 0-1], p<0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33], p=0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0-5] vs. 0 [IQR 0-2], p=0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6 [IQR 1-61], p=0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p=0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to +46%, p=0.77). Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.


Benowitz N.L.,San Francisco General Hospital
Annals of the American Thoracic Society | Year: 2014

The idea of clean nicotine delivery systems that would satisfy nicotine craving and promote smoking cessation has been considered as a possible public health tool for many years. Nicotine medications have been useful for smoking cessation but have not found widespread popularity among smokers, perhaps because of slow nicotine delivery and other sensory characteristics that differ from cigarettes. Traditional smokeless tobacco delivers as much nicotine as cigarettes and has been advocated for harm reduction but contains carcinogenic nitrosamines and has not been proven to promote cessation. Furthermore, there is concern that dual use of smokeless tobacco and cigarettes may inhibit quitting smoking. Newer oral dissolvable tobacco products contain lower levels of toxicants than other smokeless tobacco but also deliver much less nicotine and have not been popular with consumers. Electronic cigarettes that aerosolize nicotine without generating toxic tobacco combustion products have become quite popular and hold promise as a way to attract smokers away from cigarettes, although efficacy in promoting smoking cessation has not yet been demonstrated. There are concerns about safety of long-term use, and there is evidence that youth, including nonsmokers, are taking up e-cigarette use. E-cigarettes are marketed for use when one cannot smoke conventional cigarettes, and such use might result in more persistent cigarette smoking. Although their benefits and risks are being vigorously debated, e-cigarettes or other clean nicotine delivery devices could play an important role as an adjunct to a U.S. Food and Drug Administration regulatory intervention to make cigarettes less addictive and in this context could contribute to the end of cigarette smoking and smoking-induced disease. Copyright © 2014 by the American Thoracic Society.


Yee Jr. H.F.,San Francisco General Hospital
Annals of Internal Medicine | Year: 2011

To achieve the benefits of the patient-centered medical home (PCMH) model, the American College of Physicians has issued a policy paper addressing the relationship between specialist and sub-specialist physicians and PCMH practices. This paper represents a significant step toward improving care coordination and quality by demonstrating that this model is supported by numerous specialties and subspecialties, recognizing the importance of building a strong medical neighborhood, and providing a framework that will foster improvements in care at the interface of PCMHs and PCMH neighbors (PCMH-Ns). Construction of a well-functioning medical neighborhood will, however, require some refinements. First, the proposed interaction typology between PCMHs and PCMH-Ns must be expanded to include innovative forms of interaction that do not depend on traditional office visits, but for which there are clear incentives. Second, the recommended care coordination agreements must be better standardized for the sake of practicality. Finally, genuine dialogue between PCMH and PCMH-N practices needs to be realized. © 2011 American College of Physicians.


Raine T.R.,San Francisco General Hospital
Obstetrics and Gynecology | Year: 2011

Objective: To assess contraceptive discontinuation, switching, factors associated with method discontinuation, and pregnancy among women initiating hormonal contraceptives. Methods: This was a 12-month longitudinal cohort study of adolescent girls and women (n=1,387) aged 15 to 24 years attending public family planning clinics who did not desire pregnancy for at least 1 year and selected to initiate the patch, ring, depot medroxyprogesterone acetate, or pills. Participants completed follow-up assessments at 3, 6, and 12 months after baseline. Life table analysis was used to estimate survival rates for contraceptive continuation. Cox proportional hazards models were used to estimate factors associated with method discontinuation. Results: The continuation rate (per 100 person-years) at 12 months was low for all methods; however, it was lowest for patch and depot medroxyprogesterone acetate initiators, 10.9 and 12.1 per 100 person years, respectively (P≤.003); continuation among ring initiators was comparable to pill initiators, 29.4 and 32.7 per 100 person-years, respectively (P=.06). Discontinuation was independently associated with method initiated and younger age. The only factors associated with lower risk of discontinuation were greater intent to use the method and being in school or working. The pregnancy rate (per 100 person-years) was highest for patch and ring initiators (30.1 and 30.5) and comparable for pill and depot medroxyprogesterone acetate initiators (16.5 and 16.1; P<.001). Conclusion: The patch and the ring may not be better options than the pill or depot medroxyprogesterone acetate for women at high risk for unintended pregnancy. This study highlights the need for counseling interventions to improve contraceptive continuation, education about longer-acting methods, and developing new contraceptives that women may be more likely to continue. © 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

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