Place

Two studies were conducted outside of the United States, in Australia; New South Wales and Vietnam [7,9]. All remaining articles were conducted in the United States. A few locations are mentioned more than others. For example, two groups conducted their studies in Cortland County, NY [20,23]. Three groups of authors conducted their studies in Kentucky [10,21,22]. Both upstate NY and the eastern region of KY are part of the Appalachia Mountain Range and presented as rural in the research.

Similarities and differences in findings

Findings indicate that there is little research regarding interventions for opioid drug abuse in either rural or non-rural locations. The intervention that received the most attention in the review of literature was the number and distribution of Medication Assisted Treatment (MAT) for opioid use and misuse The major intervention reported in the literature was regarding efforts to increase the number of providers who can prescribe MAT for opioid use disorder in both rural and more metropolitan areas [8,13,14,20].

The Comprehensive Addiction and Recovery Act (CARA) originally authorized physicians to prescribe buprenorphine in the treatment of opioid use disorders and have been expended to include prescribers such as nurse practitioners, and physician assistants. This law was enacted in 2016 for the purpose of opioid abuse prevention and treatment. Following the enactment of CARA, there were moderate increases in the number of providers with waivers. At the conclusion of 2017, 33,876 physicians, 3,534 Nurse practitioners and 912 Physician assistants had received waivers to prescribe Buprenorphine [29]. More research is warranted in this area so interventions can be developed and implemented to increase the knowledge of prescribers and to make the use of MAT readily available. There was a dearth of literature focused on prevention of opioid abuse.

Another area deserving further research is the use of Fentanyl on the streets. Fentanyl is an opioid used to treat pain and can be used as an anesthetic drug when combined with other substances. In the literature reviewed for this paper, there was no mention of Fentanyl. However, prior to completion of this manuscript, a National Public Radio story was released that focused on the use of Fentanyl on the streets and the high overdose rates associated with its use [30]. The media indicates that Fentanyl is being used illegally on the streets along with other opioids such as Heroin. Antidotal evidence indicates overdose deaths are higher with the use of Fentanyl, which is often combined with Heroin as an additive. This is referred to as the third wave in the opioid crisis stating that prescription drug misuse was the first wave, heroin the second and Fentanyl is the third. The story did not indicate if there is a rural/urban difference in Fentanyl misuse. The incidence of misuse of Fentanyl is occurring most frequently in the eastern part of the United States [30]. The above news release can be traced back to a National Vital Statistics report from the U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics report in 2019 [31]. This warrants further study and research into the effects of this specific drug in relation to the opioid crisis.

Opioid use is increasing as supported by more than one article. For example researchers illustrated that opioid poisoning almost doubled between 2001-2011 in the state of California [12]. An international report examined four rural sites in an area of Australia and found an increase in individuals on opioid maintenance treatment over a period of four years [9]. The increase was more than 30% for three of the sites over the four years and this study referred to opioid misuse as a global crisis. No single study refuted the existence of an opioid crisis.

The questions of whether opioid use has increased more in rural than urban environments is still under debate. Research results indicated that Neonatal Abstinence Syndrome (NAS) increased 2-2.5 times per 10,000 births in rural and Appalachian counties compared to urban and non-Appalachian Kentucky counties between 2008-2014 [10]. In 2013, Kentucky NAS was more than double the national rate. Moreover, opioid facilities were further from rural and Appalachian areas compared to micropolitan/metropolitan and non-Appalachian areas (p<0.001) [10]. Similarly, the conclusion of one national study was that rural adolescents had 35% greater odds than their urban counterparts in Prescription Opioid Misuse (POM) [27]. The opioid misuse was reported as 6.8% rural, 6% small urban and 5.3% for urban adolescents. Although there is a clear trend of less POM in areas of increasing population; reporting the level of residency in three levels may have slightly inflated the odds of rural misuse over the more traditional two level comparisons. A spread in prescription opioid poisoning hospital discharges, from rural and suburban/exurban to urban areas, was found in a California state wide study [12]. One study utilized primary care patient record forms to examine the difference between rural residency and non-rural residency in obtaining opioid prescription for Non-Malignant Chronic Pain (NMCP) and found that “rural residents had higher odds of having an opioid prescription than similar non-rural adults. Rural residency was the strongest predictor for having an opioid prescription and a diagnosis for NMCP” (p.5) [18].

Although there were some studies that reported an increase of opioid use in rural areas over urban, there were a few studies that did not support this hypothesis [11,19,28]. One national study reported that prescription opioid misuse was more common in urban than rural areas; while another found no difference between the two [19,28]. Rigg and Monnat [19] speculated that previous studies finding more opioid misuse in rural areas may have had too small or a specific geographical limit in sample.

In addition to demographics, several surveys used self-report, paper and pencil instruments to measure attributes for a wide array of variables, such as alcohol disorders, chronic diseases, depression, drug abuse status, health status, mental status, opioid misuse, pain, quality of life, psychological distress, post-traumatic stress disorder and sleep disorders.

Two articles used pain scales [7,25]. One study utilized a visual analogue scale for pain assessment, with respiratory rate and blood pressure to conclude that ketamine is equitable to morphine in its analgesic effect in emergency situations where evacuation is particularly difficult [7]. One study had three pain measures, appropriate to their population of rural patients with chronic pain [25]. The first measure was a structured pain interview. The Wisconsin Brief Pain Inventory, measure of pain intensity and interference and the pain catastrophizing scale both were reported as having good psychometrics [25]. Most authors used more than one instrument for data collection.

Social determinants of health

Increase in opioid use was sometimes associated with other health disorders and socio-economic factors. Patients receiving opioid medications in rural settings have poorer overall health, higher pain levels, lower levels of education and higher rates of unemployment than their urban counterparts [11,15]. Similarly, another study showed that rural individuals who reported good health were less likely to use opioid prescriptions for non-medical reasons than those who reported poor health [28]. Studies showed that lower income and manual labor were associated with an increase in prescription opioid poisoning or prescription opioid misuse [12,19].

In addition to the general health deteriorations that are associated with opioid use or misuse, one study found an association between the hospital discharge diagnostic code, prescription opioid misuse and major psychological distress [20]. Another showed an association between Anti-Social Personality Disorder (ASPD) and hydrocodone, crack or powder cocaine, marijuana, alcohol and heroin use [21]. One study reported significant association between HCV (Hepatitis C Virus) and a network of non-medical prescription opioid users [23]. Similarly, another found a strong association between prescription opioid analgesics and positive HCV [24]. In addition, arthritis was associated with opioid use in two different studies [12,15].

The issue of ethnicity/race and opioid use is conflicting and may be shaped by media that emphasis the newness of rural opioid reports [16,18,19,28]. In exploring opioid prescription risk factors in a sample with Non-Malignant Chronic Pain (NMCP), race was reported as a factor; “being non-Caucasian was a strong predictor of having an opioid prescription and a diagnosis for NMCP” (p 5) [18]. In a study that was not limited to chronic pain patients, black and non-Hispanic residents were less likely than white urban residents to use prescription opioids for non-medical reasons [28]. Yet another concluded that white urban residents were significantly more likely to misuse prescription opioids [19]. A content analysis of a random selection of 100 popular media articles on the opioid crises reported “…a consistent contrast between criminalized urban black and Latino heroin injectors with sympathetic portrayals of suburban white prescription opioid users (p. 664) [16]. Media reporting of drug use in urbanized areas was found to be reported in stories that emphasized violence and arrests [16]. In contrast stories regarding rural drug use emphasized the unexpectedness of the problem and highlighted personal stories that humanized the individual [16].

In addition to race, social network was one of the considered variables in rural opioid use. One study reported that rural residents who have used drugs associated with network characteristics, such as having trust above the average in one’s network, had lower odds of being diagnosed with ASPD [21]. Those non-medical prescription opioid users with HCV tended to cluster together, which suggests the need for the development of a network-based intervention to prevent the spread of HCV [23]. Still another suggested the utilization of school nurses, technology and social media in opioid management [17].

Opioid use was associated with individuals with low income and manual labor jobs in a at least two studies [12,20]. Results of one study showed that lower income and manual labor were associated with an increase in the hospital discharge diagnosis of prescription opioid poisoning [12]. Another, also found those working in manual labor had higher rates of prescription opioid misuse [20].

An intersection between other demographic variables and the opioid use or misuse emerged in this review of the literature. A study by Rigg and Monnat [19] found misuse of prescription opioids were associated with other factors such as age (young), marital status (unmarried), difficult financial status and less religiosity. Unsurprisingly, these findings were similar to the findings in another national analysis of the NSDUH data set [28]. These findings indicate opioid use and misuse are influenced by different demographic variables and no one set of variables can explain an opioid problem.

Physician waivers for buprenorphine prescriptions were discussed in several articles [8,13,14,20,24]. A possible rationale for the lack of research in the published literature on waiver practices beyond that of physicians is the newness of the extension of CARA [29]. Two studies that went beyond the numbers of physicians with prescription waivers, found that there were barriers for obtaining the waiver of buprenorphine maintenance treatment [8,24]. These barriers included time, finances, clients’ needs and worries about violating patient confidentiality. After examining the Drug Enforcement Administration (DEA) list questionnaire, a different study found that family physicians were five times more likely to prescribe buprenorphine than other physicians, a statistically significant finding [24]. Only 28% of trained physicians reported prescribing buprenorphine. Abstaining from prescribing buprenorphine was associated with lack of institutional support [24].

A study in Washington state including American Indian and non-American Indian, rural and urban sites offering Opioid Assisted Treatment (OAT) found that “the number of clinics offering OAT in rural versus urban regions was significantly lower, indicating that difficulties may remain for rural residents in terms of accessing most OAT services offered in these facilities” (p. 105) [14]. One study found that the number of physicians with waivers increased in shortage counties between 2002-2011; however, opioid treatment program access remained the lowest in counties with populations less than 2,500 individuals [13].

Around 90% of physicians with waivers are located in urban areas and only about 1.3% practiced in the most rural areas [20]. These authors concluded rural residency was associated with lack of access to buprenorphine prescriptions [20].