The findings presented here are consistent with the existing literature describing the exponential growth of POD between 1993 and 2009. However, we also document the recent increase in HOD and provide initial evidence suggesting a link between the growth of PODs and the recent surge of HODs. While preliminary and not evidence of a causal relationship, the findings presented here provide empirical support for a growing concern about the commingling of prescription opioid and heroin abuse.
Consistent with the literature, we find changes in the populations most at risk for this recent opiate-related overdose epidemic. The most dramatic increases in POD are seen among whites, women (with rates exceeding that of men) and the middle-aged. Consistent with the hypothesis that prescription opioid use is creating new users of heroin, the race-adjusted rate of HOD has doubled among whites, exceeding in 2008 that of African-Americans for the first time, while also significantly increasing among 20–24 year-olds – an age group at high risk for escalating substance abuse. The rate of HOD has declined among African-Americans, perhaps reflecting generational resilience following the devastating effect of the 1960–70′s heroin epidemic on African-American communities.
The acceleration in HOD admission rates after 2006 raises fresh concerns. Previous literature declared that HOD was mostly flat during the unfolding of the prescription opioid epidemic 
. Our data reveal that from 1993 to 2006 the rate of HOD rose 69% with much of the increase occurring at the recent end of the data: from 2005 to 2009 the HOD rate increased 44%, or 11% per annum. The lagged regressions, modeling the subsequent years’ POD/HOD rates, demonstrate strong relationships between these adverse consequences. While it needs to be emphasized that these are not causal models, this finding is consistent with population level dynamics in which the same population of drug users is simultaneously using diverse opiates or migrating from one to another due to structural, market, or social forces. Indeed, the transition to heroin use is reported in several local press articles 
While consistent with the above-presented explanation other hypothesis could explain these findings. For example, heroin use may follow a cyclical pattern with generational resilience and generational forgetting (i.e. the consequences) alternating. Various socio-economic causal mechanisms may also simultaneously be responsible for both forms of opiate epidemics with little need of intertwining between them. Furthermore, hospital data undercount overdoses that result in deaths or are otherwise treated in the community. These nonhospital deaths may have a different racial or ethnic composition due to differences in community risk and other behavioral factors 
. Likewise, a lack of access to hospital or medical care may also have biased the sample, resulting in a under count of overdoses among racial or ethnic minority populations.
However, this recent experience is consistent with the historical evidence suggesting that changes in the form of opiates, their availability and the stigma attached to them coincides with changes in the population at risk for abuse and overdose. The recent rise in POD corresponds with the rise in prescription opioid availability. This in turn has been driven by a number of factors: increasing supply, pain management advocacy, pharmaceutical marketing directed to prescribers, and drug diversion. Drug diversion is a particular problem exacerbated by doctor shopping, internet sales, theft, and improper prescribing 
. Retail sales have grown 533% from 1997–2005 with hydrocodone the leading prescribed medication and oxycodone the top retailed prescription opioid by weight 
was approved in 1995 and sales rose rapidly, increasing 69-fold from $44.8 million in 1996 to $3.1 billion in 2010 
. The Drug Enforcement Agency expressed concern about the aggressive marketing of OxyContin
to physicians and responses to the prescription opioid misuse problem have been growing in number and strength since 2003 
. These include regulatory responses (drug monitoring programs and state disciplinary actions), increasing physician awareness of appropriate treatment practices and modifying drugs to reduce their potential for abuse 
. One noteworthy response followed a 2007 court case brought against the manufacturer of brand name long-acting oxycodone (OxyContin
) to which it plead guilty to falsely misrepresenting the addictive qualities of the drug compared with other pain medications 
. In the face of widespread criticism, the tablets were reformulated into a tamper proof gel tablet and approved by the FDA in 2009 
Reversal of the “pendulum swing” from under-treatment of pain to over-treatment may have intended (e.g., improved treatment of chronic pain with non-opioid modalities) and unintended consequences (e.g., former patients seeking illegitimate opiates, e.g., diverted prescription opioids or heroin) 
. Heroin use has some fluidity among certain populations and injectors may switch between opiates 
. There is a stigma threshold for heroin injection that initial prescription opioid misuse may facilitate. Once dependent, some prescription opioid misusers learn to crush, insufflate or inject their prescription opioid of choice prior to seeking heroin. Polydrug use is common among rural substance users with heroin use independently associated with prescription opioid misuse 
Preliminary observations from a companion qualitative study in inner-city Philadelphia reveal some of the market incentives for users transitioning from prescription opioids to heroin. Heroin is inexpensive and pure by historical standards and long-acting oxycodone is typically more expensive than heroin 
. Consider this rough calculation: in the early 2000’s street diverted OxyContin
OC (crushable form) cost ~$0.50 per mg (unpublished data) and heroin has had a mean street-price of $0.56/mg-pure 
; seemingly similar until one considers that the parenteral equivalent dose of heroin is 1/2 to 1/3 that of oxycodone. Furthermore, OxyContin
is now less desired as a street drug in its new tamper-resistant formulation 
There are several limitations to this study. The reliance on hospital coding for accurate diagnosis of the cause of opiate-related overdose induces some unaccountable variability. For example, hospitals may use a single code for all opiate-related overdoses, combining heroin and prescription opiates, making it difficult to distinguish specific drugs responsible for an overdose admission. Using hospital admissions rather than emergency room admissions also may affect the population by only selecting cases with more serious medical conditions. This sampling frame may result in a population that is older and with a higher prevalence of comorbid medical conditions than the opiate using population in general. Many opiate-related overdoses can be treated effectively in the ED regardless of the amount of opiate consumed and different hospitals may be more effective in treating ODs in the ED than other hospitals. We also cannot distinguish between overdoses resulting from illicit use, misuse or accidental use. Finally, using hospital admissions rather than individuals as the units of analysis we cannot control for individual level covariates or examine repeat visits in the lag models. While the degree to which the biases are unknown suggests caution in interpreting the results, the large representative sample of hospitals and random nature of many of these potential sources of errors suggests that the effect of these limitations is likely modest.
Given the dramatic increase in the rate of POD and the strong potential for current structural reforms aimed at reducing prescription opioid misuse to inadvertently shift a proportion of prescription opioid users to heroin, a robust public health response is necessary. Active surveillance looking for a rise in heroin use/users is a good starting point. Public health measures that can address and reduce overdose deaths should include primary overdose prevention e.g. treatment of substance use, including opiate substitution therapies i.e. methadone and buprenophine. Buprenorphine, a partial opiate agonist successful in treating heroin dependency 
, should be expanded to the wide variety of opiate dependent users.
Secondary prevention efforts should include national opiate overdose awareness campaigns; these could be coupled to national policies addressing prescription drug abuse 
. Tertiary overdose prevention efforts should include targeted campaigns to recognize and reverse overdose including harm reduction-based peer interventions such as rescue breathing, naloxone administration, and safe injection facilities. Evidence for the effectiveness of peer-based naloxone interventions is gathering on the local, county and statewide levels
. Indeed the stable HOD death rate compared with the rising hospitalization rate noted in this study may be suggestive of evidence for the national uptake and success of these interventions, albeit with uneven adoption and financial concerns