Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment.

BACKGROUND: Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. METHODS: Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. RESULTS: Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11). CONCLUSION: We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.

Acute Limb Ischemia Caused by Inadvertent Arterial Drug Self-Injection: A Case Report.

BACKGROUND A predictable consequence of long-term injection drug use is the destruction of the native venous system; as a consequence, people who inject drugs may eventually move to injection into skin and subcutaneous tissue, wounds, muscles, and arteries. These practices put people who inject drugs at risk for injection-related soft-tissue infection, vascular damage, ischemia, and compartment syndrome, all of which have overlapping presenting symptoms. CASE REPORT A 35-year-old man who injects drugs presented with foot swelling and discoloration initially concerning for necrotizing fasciitis or compartment syndrome. After progression despite appropriate antimicrobial and surgical treatment for soft-tissue infection, he was diagnosed with arterial insufficiency and resultant distal ischemia. This diagnosis was discovered only after obtaining additional history of the patient's drug use practices. Just prior to his symptoms, he had unintentionally injected a formed thrombus into his dorsalis pedis artery. CONCLUSIONS Intra-arterial injection of drugs can cause ischemia through a variety of mechanisms, including direct vessel trauma, arterial spasm, toxicity from the drug of abuse or an adulterant, embolism of particulate matter, and as proposed here, direct injection of preformed thrombus. Medical providers should be aware of the steps of injection drug use and their associated risks so that they can ask appropriate questions to focus their differential diagnosis, increase their understanding of common or current local injection practices, and develop rapport with the patient. Patient education on safe injection techniques may also reduce the risk of serious complications.

"The life they save may be mine": diffusion of overdose prevention information from a city sponsored programme.

BACKGROUND: Overdose remains the leading cause of death among injection drug users (IDUs) in the United States. Overdose rates are consistently high in Baltimore, MD, USA. The current qualitative study examines diffusion of information and innovation among participants in Staying Alive, an overdose prevention and naloxone distribution programme in Baltimore, MD. METHODS: In-depth interviews were conducted between June 2004 and August, 2005 with 25 participants who had completed the Staying Alive training and had reported using naloxone to revive an overdose victim. Interviews were taped and transcripts were transcribed verbatim. RESULTS: Participants were 63% male, 63% African American, and the median age was 41 years old. Participants successfully shared information on overdose prevention and management, particularly the use of naloxone, to their peers and family. CONCLUSIONS: The current study demonstrates IDUs' interest in and ability to diffuse overdose prevention information and response skills to the injection drug use community. The study underscores the importance of promoting the diffusion of information and skills within overdose prevention programmes.

A qualitative study of sexual behaviours among methamphetamine users in Chiang Mai, Thailand: a typology of risk.

INTRODUCTION AND AIMS: Methamphetamine (MA) has become the leading drug of abuse in northern Thailand over the past several years, particularly among youth. The current qualitative study explores the relationship between sexual behaviours and MA. DESIGN AND METHODS: Between March 2002 and January 2003, 48 in-depth interviews with young MA users aged 15-2 years in Chiang Mai. Interviews were transcribed verbatim in Thai and translated into English. Data were analysed inductively using the constant comparative method common to grounded theory methods. Atlas-ti was used for data management. The current analysis was stratified by gender. RESULTS: Participants were 44% male and the median age was 20 years. At the time of the interviews, 70% were not using MA. A typology of experiences with and feelings about MA's relationship to sexual activity emerged: (1) enhanced libido--individuals who found that MA enhances their sexual experiences (n = 13); (2) decreased libido or no effect--individuals who found that MA detracted from sexual desire (n = 22); and (3) virgins (n = 13). DISCUSSION AND CONCLUSIONS: Participants reported several distinct patterns of relationship between MA and sex. Tailored interventions are needed that address specific patterns of sexual behaviors among youth in order to promote sustainable safer sex behaviours in this population.

A qualitative study of overdose responses among Chicago IDUs.

BACKGROUND: Opioid overdose is a leading cause of death among injection drug users. Over half of injection drug users report at least one nonfatal overdose during their lifetime. Death from opioid overdose rarely occurs instantaneously, but rather over the course of one to three hours, allowing ample time for providing life-saving measures. In response to the prevalence of overdoses in the U.S., there are a growing number of overdose prevention and naloxone distribution programs targeting the injection drug using community. METHODS: We explored injection drug users' experiences with opioid overdose response, examining differences between overdose responses in which naloxone was and was not used. The current study is based upon qualitative interviews (N = 31) with clients of the Chicago Recovery Alliance needle exchange program who had witnessed an overdose in the past six months. The interviews explored participants' drug use history, personal overdose experiences, and details concerning their last witnessed overdose. Verbatim transcripts were coded and analyzed thematically to address major study questions. RESULTS: Participants were 81% were male, their median age was 38. They reported having injected a median of 10 years and having witnessed a median of six overdoses in their lifetime. All described overdoses were recognized and responded to quickly. None of the overdoses resulted in a fatality and naloxone was successfully administered in 58% of the last witnessed overdoses. Administering naloxone for the first time was characterized by trepidation, but this feeling dissipated as the naloxone quickly took effect. Emergency medical personnel were called in 10 of the 31 described overdoses, including four in which participants administered naloxone. The overwhelming majority of experiences with police and paramedics were positive CONCLUSION: Overall, our small study found that the overdose prevention efforts build on extensive knowledge possessed by IDUs. Teaching IDUs how to use naloxone is an effective risk reduction strategy.

Purine nucleosides stimulate Na/K ATPase, and prolong survival in hemorrhagic shock.

BACKGROUND: Hemorrhagic shock leads to the appearance of substances in plasma that depress Na/K ATPase activity leading to a rise in plasma potassium. Recently, we reported that adenosine can stimulate Na/K ATPase activity, lower the plasma potassium back to control and prolong survival in shocked rats. However, adenosine also caused bradycardia. We therefore searched for adenosine analogs that stimulate Na/K ATPase without the side effects of bradycardia. METHODS: Na/K ATPase activity was assessed using Rb uptake in erythrocytes. Pentobarbital anesthetized rats had their femoral artery and vein cannulated, bled to 35 mm Hg for 1 hour and resuscitated. RESULTS: We found that the purine nucleosides, inosine, guanosine, adenosine, deoxyadenosine and deoxyguanosine, stimulated Na/K ATPase in a dose-dependent manner and overcame partial inhibition by ouabain. However, the de-ribosylated bases, the nucleotides and the pyrimidines had little or no effect on Na/K ATPase activity. Purine nucleosides did not stimulate Na/K ATPase activity through adenosine receptors, as caffeine (1 mmol/L) or aminophylline (1 mmol/L) did not block stimulation. However, stimulation was blocked by inhibitors of the equilibrative nucleoside transporter (dipyridamole, 1 mmol/L, or S-(4-nitrobenzyl)-6-thioinosine, 10 micromol/L), suggesting that the mechanism of action is intracellular. Inosine, guanosine and adenosine (2.5 mmol/L) significantly increased survival of rats in hemorrhagic shock as compared with saline and cytidine controls, and lowered the shock-elevated plasma K. CONCLUSIONS: Purine nucleosides stimulate Na/K ATPase and prolong survival in hemorrhagic shock in rats, probably through an intracellular mechanism.

Adenosine stimulates NA/K ATPase and prolongs survival in hemorrhagic shock.

BACKGROUND: Hemorrhagic shock leads to the appearance of substances in plasma that can change Na/K ATPase activity. Our laboratory has reported the existence of a plasma inhibitor of Na/K ATPase that appears during shock. Recently, we have isolated a substance in plasma that stimulates Na/K ATPase. METHODS: Using liquid chromatography, we found a fraction of plasma that simulated Na/K ATPase. The purified substance was identified as adenosine by its UV spectrum. Na/K ATPase activity was assessed using 86Rb uptake in erythrocytes. RESULTS: Plasma from rat, dog, and calf stimulated Na/K ATPase activity in a dose-dependent manner and this stimulation was inhibited by ouabain. Commercial adenosine also stimulated Na/K ATPase in a dose-dependent manner and was inhibited by ouabain. Na/K ATPase was not stimulated by ATP, ADP, AMP adenine, hypoxanthine, xanthine or uric acid. Stimulation by adenosine (1 mmol/L) was not affected by adenosine receptor antagonists, caffeine (1 mmol/L) or aminophylline (1 mmol/L). However, the stimulation was inhibited by the nucleoside transport blocker, dipyridamole, suggesting that adenosine acts inside the cell. Adenosine (0.5 mmol/L) given to rats in hemorrhagic shock survived longer suggesting that stimulation of Na/K ATPase prolongs survival during hemorrhagic shock. CONCLUSION: Adenosine stimulates Na/K ATPase and prolongs survival in hemorrhagic shock, possible by reversing or overcoming the effects of an endogenous inhibitor of Na/K ATPase, as it does for ouabain. The effect of adenosine on Na/K ATPase is not mediated through adenosine receptors and probably results from an intracellular process.

Inosine infusion prevents mortality in endotoxic shock.

BACKGROUND: Substances that inhibit Na/K ATPase activity appear in plasma during severe septic shock causing Na and fluid to move into cells and K to move out, resulting in cell swelling and an elevation of plasma K. These changes contribute to the morbidity of sepsis. Recently, we reported that inosine and other purine nucleosides stimulate Na/K ATPase activity, prolong survival in hemorrhagic shock, and lower the plasma potassium in that condition. Here, we determine whether inosine prolongs survival in lipopolysaccharide-induced sepsis shock. METHODS: Pentobarbital-anesthetized rats underwent cannulation of a femoral artery and vein, and lipopolysaccharide was injected by intravenous bolus (10 mg/kg). Rats were than resuscitated (5 mL/hr) with inosine (5 mmol/L) in saline, saline alone, inosine with S-4-nitrobenzyl-6-thioinosine (NBTI, 10 micromol/L, an equilibrative nucleoside transporter blocker), NBTI alone, or no resuscitation. RESULTS: Inosine significantly and dramatically prolongs survival of rats in endotoxic shock as compared with saline resuscitation or to no resuscitation. Furthermore, resuscitation with NBTI (10 micromol/L) prevented prolonged survival with inosine. CONCLUSION: Inosine prevents mortality in lipopolysaccharide-induced septic shock in rats. The mechanism of action must be intracellular, as blockers of the equilibrative nucleoside transporter prevented prolonged survival with inosine.

Comparison of the influence of rostral and caudal raphe neurons on the adrenal secretion of catecholamines and on the release of adrenocorticotropin in the cat.

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after chemical stimulation of medial brain-stem regions, including those that influence nociceptive input to the medullary or spinal dorsal horn. Microinjections of L-glutamate (0.5 M, 160 nl) were directed at the following rostral and caudal raphe nuclei: the periaqueductal gray (PAG), the dorsal raphe nucleus (DR), the raphe magnus (RM), and the raphe obscurus/raphe pallidus (Ro/Rpa). Activation of DR neurons evoked a significant increase in the adrenal secretion of epinephrine (+2.6 +/- 1.1 ng/min, P less than 0.01) that returned towards prestimulus values by 6 min, whereas microinjections into other raphe nuclei had no consistent effect. Activation of Ro/Rpa neurons evoked an increase in the plasma concentration of adrenocorticotropin (ACTH, +47.9 +/- 12.3 pg/ml, P less than 0.01), whereas microinjections into other raphe nuclei did not affect ACTH. Arterial pressure increased significantly after activation of PAG (+7.5 +/- 2.1 mm Hg, P less than 0.01) or of DR (+4.8 +/- 2.0 mm Hg, P less than 0.05) neurons, whereas heart rate increased significantly (P less than 0.05) after stimulation of cells within the Ro/Rpa. Glutamate microinjections within the RM, a raphe nucleus that exerts a significant descending influence on nociceptive input to the medullary and to the spinal dorsal horns, had no consistent effect on any measured variable. No evidence was seen to suggest that chemical activation of neurons within raphe nuclei inhibited the adrenal secretion of catecholamines or inhibited the release of ACTH. The results indicated that glutamate activation of neurons within different raphe nuclei evoked non-uniform effects on neuroendocrine and autonomic function. Further, these data suggested that the neural substrate underlying the control of the adrenal secretion of catecholamines and of the release of ACTH in response to activation of raphe neurons is likely distinct from that which contributes to the descending influence on nociceptive input to the medullary and spinal dorsal horn.

Glutamate activation of neurons within trigeminal nucleus caudalis increases adrenocorticotropin in the cat.

The role of trigeminal nucleus caudalis (Vc) in control of the autonomic and endocrine correlates of nociception was assessed in chloralose-anesthetized cats. Microinjections of the neuroexcitatory agent, L-glutamate (0.5 M), were directed at the marginal layers, at the central magnocellular portion, and at the deep magnocellular portion of Vc. Changes in the plasma concentration of adrenocorticotropin (ACTH), in mean arterial pressure, and in heart rate were examined. Glutamate excitation of neurons within the marginal layers of Vc evoked a significant (+143 +/- 52 pg/ml, P less than 0.01) increase in plasma ACTH during the 10 min postinjection sampling period. Glutamate injections into the deep magnocellular portion of Vc also increased plasma ACTH (+97 +/- 28 pg/ml, P less than 0.05), whereas activation of neurons in the central magnocellular portion of Vc had no consistent effect on plasma ACTH (-25 +/- 29 pg/ml, P greater than 0.10). Arterial pressure increased transiently after glutamate injections into the marginal layers or central magnocellular portion of Vc, whereas injections into the deep magnocellular portion of Vc did not affect arterial pressure. Heart rate increased transiently regardless of the laminar site of injection within Vc. These data indicate that activation of neurons in laminar regions of Vc that process nociceptive information cause an increase in plasma ACTH, whereas activation of neurons in laminae of Vc that process mainly non-nociceptive input have no significant influence on plasma ACTH.