Publications

BACKGROUND

As resources are deployed to address the opioid overdose epidemic in the USA, it is essential that we understand the correlates of more frequent opioid injections-which has been associated not only with HIV and HCV transmission, but also with overdose risk-to inform the development and targeting of effective intervention strategies like overdose prevention and naloxone distribution programs. However, no studies have explored how characteristics of opioid use partnerships may be associated within injection frequency with opioid partnerships.

METHODS

Using baseline data from a trial of a behavioural intervention to reduce overdose among opioid users in San Francisco, CA, we calculated assortativity among opioid use partnerships by race, gender, participant-reported HIV- and HCV-status, and opioids used using Newman's assortativity coefficient (NC). Multivariable generalized estimating equations linear regression was used to examine associations between individual- and partnership-level characteristics and injection frequency within opioid use partnerships.

RESULTS

Opioid use partnerships (n=134) reported by study participants (n=55) were assortative by race (NC=0.42, 95%CI=0.33-0.50) and participant-reported HCV-status (NC=0.42, 95%CI=0.31-0.52). In multivariable analyses, there were more monthly injections among sexual/romantic partnerships (β=114.4, 95%CI=60.2-168.7, p<0.001), racially concordant partnerships reported by white study participants (β=71.4, 95%CI=0.3-142.5, p=0.049), racially discordant partnerships reported by African American study participants (β=105.7, 95%CI=1.0-210.5, p=0.048), and partnerships in which either member had witnessed the other experience an overdose (β=81.8, 95%CI=38.9-124.6, p<0.001).

CONCLUSION

Social segregation by race and HCV-status should potentially be considered in efforts to reach networks of opioid users. Due to higher injection frequency and greater likelihood of witnessing their partners experience an overdose, individuals in sexual/romantic opioid use partnerships, white individuals in racially homogenous partnerships, and African American individuals in heterogeneous partnerships may warrant focused attention as part of peer- and network-based overdose prevention efforts, as well as broader HIV/HCV prevention strategies. Developing and targeting overdose prevention education programs that provide information on risk factors and ways to identify overdose, as well as effective responses, including naloxone use and rescue breathing, for more frequently injecting networks may help reduce opioid morbidity and mortality in these most at risk groups.

 Precut papillotomy is widely used after failed biliary cannulation. Endoscopic ultrasound (EUS)-guided biliary access techniques are newer methods to facilitate access and therapy in failed cannulation. We evaluated the impact of EUS-guided biliary access on endoscopic retrograde cholangiopancreatography (ERCP) success and compared these techniques to precut papillotomy.  We retrospectively compared two ERCP cohorts. One cohort consisted of biliary ERCPs (n = 1053) attempted in patients with native papillae and surgically unaltered anatomy in whom precut papillotomy and/or EUS-guided biliary access were routinely performed immediately after failed cannulation. This cohort was compared with a similar ERCP cohort (n = 1062) in which only precut papillotomy was available for failed cannulation. The following outcomes were compared: conventional cannulation success, rates of attempted advanced access techniques (precut or EUS), precut success, EUS-guided biliary access success, and ERCP failure rates.  Although conventional cannulation success, rates of attempted advanced access technique (precut or EUS), and precut success were similar, the ERCP failure rate was lower when both EUS-guided biliary access and precut were available (1.0 % [95 % confidence interval (CI) 0.4 - 1.6]), compared with when only precut was possible for failed access (3.6 % [95 %CI 2.5 - 4.7];  < 0.001). Success for EUS-guided biliary access (95.1 % [95 %CI 89.7 - 100]) was significantly higher than for precut (75.3 % [95 %CI 68.2 - 82.4];  < 0.001), and mainly due to superiority in malignant obstruction (93.5 % vs. 64 %;  < 0.001). EUS-guided biliary access decreases the rate of therapeutic biliary ERCP failure. Our results support the use of EUS-guided biliary access to optimize single-session ERCP success. In experienced hands, these techniques appear as effective, if not more so, than precut papillotomy.

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders.

BACKGROUND

Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention.

METHODS

We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention.

RESULTS

We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women), ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women), ~90% of the benefit of testing all women would be derived.

CONCLUSION

SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.