Publications

BACKGROUND

Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile.

OBJECTIVE

To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone.

METHODS AND MATERIALS

Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial. Cabazitaxel 20 and 25mg/m were each evaluated in combination with escalating doses of mitoxantrone (starting dose 4mg/m), given with prednisone 5mg twice daily.

RESULTS

A total of 25 patients were enrolled, with median age of 67 (range: 51-78) and prostate-specific antigen of 66.8ng/ml (range: 3-791.2). There were 4 dose-limiting toxicities (febrile neutropenia, n = 3; sepsis, n = 1). The maximally tolerated dose was cabazitaxel 20mg/m plus mitoxantrone 12mg/m. The most common treatment-related grade≥3 related adverse events included neutropenia (n = 8; 32%), febrile neutropenia (n = 5; 20%), and thrombocytopenia (n = 4; 16%). The median number of treatment cycles was 8 (range: 2 to 19+). Decline in prostate-specific antigen to≥50% from baseline was observed in 15 patients (60%). Objective responses were observed in 10/14 (71%) evaluable patients. The median radiographic progression-free survival was 14.5 months (95% CI: 8.0-not reached (NR)), and median overall survival was 23.3 months (95% CI: 14.3-NR).

CONCLUSIONS

The approved single-agent doses of mitoxantrone and cabazitaxel were safely combined. The combination led to durable tumor responses in most patients. Further study of the combination is warranted.

Importance

Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit.

Objective

To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older.

Design, Setting, and Participants

This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization.

Main Outcomes and Measures

Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living.

Results

The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively). In contrast, little evidence of functional decline due to β-blockers was found in participants with intact cognition or mild dementia (OR, 1.03; 95% CI, 0.89-1.20; P = .03 for effect modification) or in those in the best (OR, 0.99; 95% CI, 0.77-1.26) and intermediate (OR, 1.05; 95% CI, 0.86-1.27) tertiles of functional independence (P = .06 for effect modification). Mortality benefits of β-blockers were similar across all subgroups.

Conclusions and Relevance

Use of β-blockers after AMI is associated with functional decline in older nursing home residents with substantial cognitive or functional impairment, but not in those with relatively preserved mental and functional abilities. Use of β-blockers yielded a considerable mortality benefit in all groups.

OBJECTIVE

Advanced Automatic Collision Notification (AACN) services in passenger vehicles capture crash data during collisions that could be transferred to Emergency Medical Services (EMS) providers. This study explored how EMS response times and other crash factors impacted the odds of fatality. The goal was to determine if information transmitted by AACN could help decrease mortality by allowing EMS providers to be better prepared upon arrival at the scene of a collision.

METHODS

The Crash Injury Research and Engineering Network (CIREN) database of the US Department of Transportation/National Highway Traffic Safety Administration (USDOT/NHTSA; Washington DC, USA) was searched for all fatal crashes between 1996 and 2012. The CIREN database also was searched for illustrative cases. The NHTSA's Fatal Analysis Reporting System (FARS) and National Automotive Sampling System Crashworthiness Data System (NASS CDS) databases were queried for all fatal crashes between 2000 and 2011 that involved a passenger vehicle. Detailed EMS time data were divided into prehospital time segments and analyzed descriptively as well as via multiple logistic regression models.

RESULTS

The CIREN data showed that longer times from the collision to notification of EMS providers were associated with more frequent invasive interventions within the first three hours of hospital admission and more transfers from a regional hospital to a trauma center. The NASS CDS and FARS data showed that rural collisions with crash-notification times >30 minutes were more likely to be fatal than collisions with similar crash-notification times occurring in urban environments. The majority of a patient's prehospital time occurred between the arrival of EMS providers on-scene and arrival at a hospital. The need for extrication increased the on-scene time segment as well as total prehospital time.

CONCLUSION

An AACN may help decrease mortality following a motor vehicle collision (MVC) by alerting EMS providers earlier and helping them discern when specialized equipment will be necessary in order to quickly extricate patients from the collision site and facilitate expeditious transfer to an appropriate hospital or trauma center. Plevin RE , Kaufman R , Fraade-Blanar L , Bulger EM . Evaluating the potential benefits of advanced automatic crash notification. Prehosp Disaster Med. 2017;32(2):156-164.

BACKGROUND

Substance use is common among men who have sex with men (MSM) worldwide, and epidemiologic data suggest that alcohol/substance-using MSM are at greater risk for HIV. However, there are scarce data on substance abuse treatment programs (SATPs) for substance-using MSM.

OBJECTIVES

We examined proportions of substance use as well as SATP availability and use. We used multivariable regression models, controlling for potential confounders, to examine behavioral and demographic correlates of SATP availability and use.

METHODS

This is a cross-sectional study of a multi-region, online sample of substance-using MSM.

RESULTS

In this sample, 75% were substance-using MSM of whom 36% reported at-least-weekly use. Substance use was most prevalent among respondents from Eastern Europe/Central Asia (86%) and Latin America (79%). Among substance-using MSM, 96% and 33% reported alcohol intoxication and other substance use, respectively; 11% reported having high SATP availability; and 5% reported using SATPs. Controlling for global region of origin and age, high SATP availability was associated with high access to HIV risk-reduction education (aOR = 3.19; CI = 1.48-6.89), mental health services (aOR = 2.53; CI = 1.32-4.83), and medical care (aOR = 2.32; CI = 1.12-4.80); less than college-level education (aOR = 0.32; CI = 0.18-0.54); and higher comfort levels with providers (aOR = 1.75; CI = 1.30-2.37). Controlling for substance use frequency and personal income additionally, using SATPs was associated with higher levels of connection to the gay community (aOR = 2.76; CI = 1.22-6.22).

CONCLUSION

In this global sample of MSM, we found high alcohol intoxication and other substance use proportions. Few substance-using MSM report SATP availability, highlighting the need to develop novel substance use programs outside traditional treatment settings.