Infections In Drug Users

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  • Table 1. Organisms Responsible for Bacterial Infections in Drug Users.
  • Table 2. Initial Management of Bacterial Infectious Syndromes among Suspected Drug Users.
  • Infections In Drug Users

    1. 1. Infections in Drug Users Tahseen J. Siddiqui, M.D
    2. 2. Introduction <ul><li>Annually, ~5 % of the global population, or 200 million people, use illicit drugs </li></ul><ul><li>In U.S.19.5 million people 12 years of age or older, or 8.2 % of the population, had used an illicit drug in the prior month </li></ul><ul><li>Estimated 13 million injection-drug users worldwide, 78% in developing nations </li></ul><ul><li>Infections are among the most serious complications of drug use </li></ul><ul><li>Drug use plays a major role in the transmission of HIV, STD, viral hepatitis and a diversity of bacterial infections </li></ul>
    3. 3. Drug Situation: Chicago <ul><li>Chicago is the major transportation hub and distribution center for illegal drugs throughout the Midwest </li></ul><ul><li>drug trafficking groups: Mexico-based poly-drug organizations, Colombian cocaine and heroin trafficking organizations, and Nigerian/West African groups trafficking in Southeast and Southwest Asian heroin. </li></ul><ul><li>Chicago-based street gangs such as the Gangster Disciples, Vice Lords, and Latin Kings control the distribution and retail sale of cocaine, heroin, and marijuana </li></ul>2005 Federal Drug Seizures   Cocaine: 2,623.2 kgs.   Heroin: 24.1 kgs.   Methamphetamine: 14.2 kgs./3,181 du   Marijuana: 2,546.2 kgs.   Hashish: 3.7 kgs   MDMA: 0.3 kgs/78,901 du   Meth Lab Incidents: 931 (DEA, state, and local)
    4. 4. Drugs The Methods of Adm in istration
    5. 5. Marijuana <ul><li>Marijuana (&quot;grass&quot;; &quot;pot&quot;; &quot;reefer&quot;; &quot;joint&quot;; &quot;hashish&quot;; &quot;cannabis&quot;; &quot;weed&quot;) - 1 in 3 Americans has used marijuana at least once and ~10% of the population uses it on a regular basis </li></ul><ul><li>Source-the hemp plant (cannabis sativa) and its content of THC (delta-9-tetrahydrocannabinol) and other cannaboids found in the leaves and flowering shoots of the plant. </li></ul><ul><li>The effects - may be noted within seconds to minutes after inhaling the smoke (from a joint or a pipe) or within 30 to 60 minutes after ingestion (eating foods containing marijuana such as brownies) </li></ul>
    6. 6. <ul><li>SE: Euphoria, relaxation, increased visual, auditory, and taste perceptions and appetite (&quot;munchies&quot;) > depersonalization, changed body image, incoordination, disorientation and acute panic reactions- &quot;bad trips&quot; or severe paranoia, delirium and hallucinations, blood-shot eyes; tachycardia, hypertension, bronchodilatation or asthma , bronchitis, pharyngitis, and sinusitis, </li></ul><ul><li>Withdrawal effects: agitation , insomnia, anxiety </li></ul><ul><li>Medical properties: treatment of nausea (chemotherapy), Others claim that appetite stimulant in AIDS or useful in glaucoma. Its active ingredient (dronabinol) approved by the FDA for these purposes </li></ul>Marijuana
    7. 7. Cocaine <ul><li>May be inhaled through the nose (&quot;snorting&quot;) or dissolved in water and administered intravenously. smokeable form known as freebase or &quot;crack.&quot; </li></ul><ul><li>When mixed with heroin , in a single syringe for IV use, the combination is referred to as a &quot;speedball.&quot; </li></ul><ul><li>SE: Smoking produces an instant and intense but very short lived euphoria, local anesthesia, potent CNS stimulation, increased confidence, energy, decreased inhibitions. extremely pleasurable high, mood swings, depression , sleep/behavior disorder, memory loss, and social withdrawal. </li></ul>
    8. 8. Crack cocaine <ul><li>Crack cocaine produced by dissolving powdered cocaine in a mixture of water and ammonia or sodium bicarbonate (baking soda). The mixture is boiled until a solid substance forms. The solid is removed from the liquid, dried, and then broken into the chunks (rocks) that are sold as crack cocaine. </li></ul>
    9. 9. Cocaine Smoking Crack Cocaine
    10. 10. Cocaine
    11. 11. Heroin <ul><li>FDA considered heroin abuse to be the # 1 drug problem until 1986, when cocaine took the lead </li></ul><ul><li>Heroin is still used regularly by 1.5 million in U.S </li></ul><ul><li>Most prefer to inject heroin, because the intravenous and subcutaneous routes give a faster, more intense peak effect and because the potency of much street heroin is low </li></ul><ul><li>Signs of recent heroin injection are phlebitis and bruises from multiple needlesticks. Long-term abuse often causes varying degrees of scarring </li></ul>
    12. 12. Heroin <ul><li>In the liver, heroin undergoes deacetylation to morphine, which is then excreted in the urine. Thus, drug testing for heroin is designed to detect morphine in the urine. As drug testing becomes increasingly common, it is important to be aware that commercial poppy seeds may contain enough morphine or codeine to produce positive results on urinalysis. </li></ul>
    13. 13. Heroin Heroin comes in a white to brown powder or a dark tar-like substance, and is sold in a variety of packaging The most popular form of heroin is a dark tar-like substance called black tar, which is sold in small foil or cellophane packets or in small toy balloons. The most common use of heroin is by injection (called &quot;mainlining&quot; or &quot;shooting&quot;), but in it's powder form it can be inhaled through the nose or smoked.
    14. 14. Black tar heroin and the paraphernalia for injecting and storing the drug Paraphernalia for injecting heroin include hypodermic needles, small cotton balls used to strain the drug, and water and spoons or bottle caps used for &quot;cooking&quot; or liquefying the heroin. Paraphernalia for inhaling or smoking heroin includes razor blades, straws, rolled dollar bills, and pipes. The high from the drug usually lasts from four to six hours.
    15. 15. Selected street names and adverse effects of illicit drugs <ul><li>CANNABINOIDS </li></ul><ul><li>Marijuana and hashish </li></ul><ul><li>Bag, Colombian, doobie, dope, grass, hash, hump, Jay, joint, lid, Mary Jane, pot, reefer, sinsemilla, weed </li></ul><ul><li>Red eyes, neglect of appearance, loss of interest and motivation, possible weight loss </li></ul>
    16. 16. <ul><li>OPIATES </li></ul><ul><li>Heroin </li></ul><ul><li>Black tar, China white, dog food, dreamer, dust, H, horse, junk, scag, smack </li></ul><ul><li>Addiction, severe withdrawal symptoms, loss of appetite, death from overdose </li></ul>Selected street names and adverse effects of illicit drugs
    17. 17. <ul><li>STIMULANTS </li></ul><ul><li>Cocaine </li></ul><ul><li>Bernice, blow, C, coke, crank, flake, freeze, jam, lady, leaf, snow, stardust, toot, white lady </li></ul><ul><li>Addiction, hypertension, sleeplessness, restlessness, anxiety, lung and nasal damage, intense high followed by frequent dysphoria, loss of appetite, intense psychological dependence, death from overdose </li></ul>Selected street names and adverse effects of illicit drugs
    18. 18. <ul><li>Amphetamines </li></ul><ul><li>Bennies, black beauties, copilots, crank, crystal, dexies, eye opener, footballs, glass, hearts, ice, ice cream, lid, meth, moth, quartz, speed, uppers </li></ul><ul><li>Addiction, hypertension, loss of appetite, paranoia, hallucinations, coma, convulsions, excessive irritability, nervousness, mood swings, hyperactivity, brain damage, death from overdose </li></ul>Selected street names and adverse effects of illicit drugs
    19. 19. <ul><li>HALLUCINOGENS </li></ul><ul><li>Lysergic acid diethylamide (LSD) Acid, </li></ul><ul><li>barrels, blotters, blue heaven, California sunshine, cubes, domes, flats, frogs, lids, microdot, purple haze, sugar cubes, windowpanes </li></ul><ul><li>Dilated pupils, hallucinations, illusions, mood swings, flashback, breaks from reality, emotional breakdown </li></ul>Selected street names and adverse effects of illicit drugs
    20. 20. Selected street names and adverse effects of illicit drugs <ul><li>Mescaline and psilocybin </li></ul><ul><li>Buttons, cactus, magic mushrooms, mesc, TMA (a mixture of mescaline, LSD, and marijuana) </li></ul><ul><li>Dilated pupils, hallucinations, illusions, mood swings, breaks from reality, emotional breakdown </li></ul>
    21. 21. Selected street names and adverse effects of illicit drugs <ul><li>Phencyclidine (PCP) </li></ul><ul><li>Angel dust, clicker, crystal, dummy dust, hog, horse, killer, krystal joints, love, mint weed, PeaCe Pill, sherms, super grass, weed </li></ul><ul><li>Slurred speech, blurred vision, confusion, agitation, aggression, ataxia, anxiety, depression, impaired memory and perception, acute psychosis, convulsions, increased heart rate and blood pressure, death from accidents or overdose </li></ul>
    22. 22. Selected street names and adverse effects of illicit drugs <ul><li>Methylated amphetamines </li></ul><ul><li>(&quot;designer drugs&quot;) Adam, China white, ecstasy, Eve, love drug, MDA, X, XTC </li></ul><ul><li>Hypertensive crisis, hallucinations, nausea, confusion, sleeplessness, increased blood pressure, profuse sweating, mood elevation </li></ul>
    23. 23. Crystal Methamphetamine <ul><li>“ Ice and Glass” colorless, odorless form of d-methamphetamine resembles small fragments of glass or shiny blue-white &quot;rocks&quot; of various sizes. </li></ul><ul><li>has a higher purity level and may produce even longer-lasting and more intense physiological effects than the powdered form of the drug. </li></ul><ul><li>typically is smoked using glass pipes similar to pipes used to smoke crack cocaine. </li></ul><ul><li>Crystal methamphetamine also may be injected. </li></ul>
    24. 24. Epidemiology <ul><li>Most bacterial infections among drug users are caused by commensal flora, with Staphylococcus aureus and streptococcus . </li></ul><ul><li>Outbreaks caused by unusual organisms, such as clostridia species and Pseudomonas aeruginosa , indicate a particular drug or drug-use behavior </li></ul><ul><li>Skin and soft-tissue infections are most common </li></ul><ul><li>Study of injection-drug users in San Francisco found that 32 % had an abscess, cellulitis, or both </li></ul>
    25. 25. Epidemiology <ul><li>Injection-drug users who lack viable veins for use commonly resort to &quot;skin popping&quot; (subcutaneous or intramuscular injection) and have higher risk of soft-tissue infection </li></ul><ul><li>Injecting &quot;speedballs&quot; (mixtures of cocaine and heroin) and HIV infection were also associated with skin abscesses </li></ul><ul><li>Using dirty needles, failing to clean the skin before injection, and &quot;booting&quot; (repeatedly flushing and pulling back during injection) may also increase the risk of abscess </li></ul><ul><li>An upsurge in skin infections, primarily abscesses, as well as, necrotizing fasciitis among injection-drug users has been caused by CA-MRSA </li></ul>
    26. 26. Epidemiology <ul><li>Infective Endocarditis (IE): incidence 1.5 to 3.3 cases per 1000 injection-drug users per year </li></ul><ul><li>Colonization with S. aureus, history of IE, HIV (<200 CD4) and cocaine use - contribute </li></ul><ul><li>Community-Acquired Pneumonia: ( Aspiration ) </li></ul><ul><li>10-fold increase, smoking, malnutrition, HIV infection contribute </li></ul><ul><li>Pulmonary Tuberculosis : Risk factors > crowded living conditions (homeless shelters, &quot;crack&quot; cocaine houses and &quot;shooting galleries&quot;), delays in diagnosis, poor adherence to treatment and HIV/AIDS </li></ul><ul><li>“ Shotgunning&quot; (smoking and inhaling a drug and then expelling the smoke into another person's mouth), a common practice among smokers of crack cocaine </li></ul><ul><li>Inhaling cocaine also predisposes drug users to upper respiratory tract infections, including Sinusitis and Septal Abscesses </li></ul>
    27. 27. Pathogenesis <ul><li>Bacteria causes infections in drug users are acquired: </li></ul><ul><ul><li>Drug user's commensal flora </li></ul></ul><ul><ul><li>Organisms contaminating the drugs, drug adulterants, or paraphernalia </li></ul></ul>
    28. 28. Role of Commensal Flora <ul><li>Drug users have a higher rate of nasal or skin colonization with S. aureus </li></ul><ul><li>Infections occur when commensal flora is introduced into the surrounding tissues or bloodstream through injection </li></ul><ul><li>Poor hygiene may exacerbate the risk - fail to clean injection sites. injecting at heavily colonized sites (femoral vein- gram-negative flora), crushing capsules/tablets in mouth when preparing them for IV injection, blowing out needle clots or licking needles to facilitate injection (oral streptococcal and anaerobic species) </li></ul><ul><li>Equipment may be rinsed only with water, or saliva or even with toilet water </li></ul>
    29. 29. Sharing of Drug Paraphernalia <ul><li>Studies suggest that S. aureus and Streptococcus pyogenes transmits through drug-use networks and shared drug paraphernalia </li></ul><ul><li>In the first U.S. outbreak of CA-MRSA among injection-drug users, the epidemic strain was cultured from a needle used by one of the patients </li></ul><ul><li>In Boston outbreak of S. aureus bacteremia in injection-drug users caused by a single strain ,injected by a &quot;street doctor&quot; at the same &quot;shooting gallery&quot; using the gallery's drug paraphernalia </li></ul><ul><li>Study showed 26 %) of inhalational drugs users had nasal colonization with S. aureus and 8 % of their inhalational paraphernalia were positive for S. aureus . (Quagliarello et al) </li></ul>
    30. 30. Transmission through Drugs or Drug Adulterants and Drug Preparation <ul><li>Black-tar heroin becomes contaminated with clostridial spores when mixed with adulterants (e.g., methamphetamine or strychnine) or diluted (&quot;cut&quot;) with substances such as dextrose or dyed paper </li></ul><ul><li>The iv combination of pentazocine (an analgesic) and tripelennamine (an antihistamine), referred to as &quot;Ts and Blues,&quot; or TaBs , which was popular in Chicago in the late 1970s, caused an outbreak of infective endocarditis due to P. aeruginosa at Cook County Hospital - The tablets were crushed and then mixed with warm tap water before injection </li></ul><ul><li>A series of groin abscesses due to S. milleri in Scotland, where it was common to crush buprenorphine (an opioid) and temazepam (a benzodiazepine) between the teeth and then inject it after cleaning the skin with saliva </li></ul>
    31. 31. Gordon R and Lowy F. N Engl J Med 2005;353:1945-1954 Organisms Responsible for Bacterial Infections in Drug Users
    32. 32. Skin, Soft-Tissue & Musculoskeletal Infections <ul><li>Result from nonsterile injections, sharing of equipment, poor personal hygiene, subcutaneous injection into deltoid muscles and thighs and injection into the veins of the neck or groin. </li></ul><ul><li>Staphylococcus aureus is the main agent, (replacing Candida Sp. & Pseudomonas) followed by various streptococci, aerobic gram-negative rods, anaerobic cocci, and bacilli A syndrome of severe dermatitis, eosinophilia, and dermatopathic lymphadenopathy has recently been described in two intravenous drug users with dual infection with HIV </li></ul>
    33. 33. Skin, Soft-Tissue & Musculoskeletal Infections <ul><li>Community-associated MRSA should be considered as a potential cause of skin & soft tissue abscesses in all injection drug users </li></ul><ul><li>Septic arthritis and osteomyelitis , (vertebral spine/knee/sternoclavicular and sacroiliac joints) from hematogenous seeding or local extension of a skin or soft-tissue infection </li></ul><ul><li>Injecting in high-risk areas such as the jugular vein (&quot;pocket shot&quot;) and femoral vein (&quot;groin hit&quot;) </li></ul><ul><li>More likely to be polymicrobial or anaerobic </li></ul>
    34. 34. Skin, Soft-Tissue & Musculoskeletal Infections <ul><li>From transient rheumatologic prodrome of hepatitis B antigenemia to chronic amyloidosis </li></ul><ul><li>Cocaine can cause muscle and skin infarction and rhabdomyolysis after &quot;free-basing&quot; cocaine, sometimes with renal failure and shock after intravenous injection or inhalation of free-base cocaine (crack) or both </li></ul><ul><li>Rhabdomyolysis and shock has been reported due to intravenous methamphetamine or phenmetrazine or with heroin. </li></ul>
    35. 35. Heroin Skin, Soft-Tissue & Musculoskeletal Infections
    36. 36. Heroin Skin, Soft-Tissue & Musculoskeletal Infections
    37. 37. Skin, Soft-Tissue & Musculoskeletal Infections Soft-Tissue Abscess on the Leg of an Injection-Drug User. &quot;Track&quot; marks from injections extend along the calf. Provided courtesy of Robert Gwizdala. CA-MRSA PDF MRI in an Injection-Drug User with Vertebral Osteomyelitis Involving T6–T7 (Arrow) with an Adjacent Epidural Abscess. Culture grew Enterobacter cloacae .
    38. 38. Endovascular Infections <ul><li>Infective endocarditis, septic thrombophlebitis (septic PE), mycotic aneurysms (subclavian, carotid and pulmonary arteries) , and sepsis, are among the most serious complications of injection-drug use </li></ul><ul><li>Infective endocarditis is most commonly due to S. aureus (including MRSA) and involves the tricuspid valve in 70 % of patients </li></ul><ul><li>Other organasims-streptococci, gram-negative bacilli ( Pseudomonas aeruginosa-use of pentazocine and tripelennamine (&quot;T's and blues&quot;) in Detroit ), Serratia (San Francisco), respiratory flora, Candida , anaerobes- polymicrobial infections </li></ul><ul><li>Symptoms may include fever, dyspnea, pleuritic chest pain, and cough </li></ul><ul><li>The mortality rate < 5 percent (high in AIDS) </li></ul><ul><li>Treatment for 2-4 weeks of ABX therapy (Nafcillin/Vancomycin/D aptomycin/, Gentamicin/Rifampin) </li></ul>
    39. 39. Tricuspid Endocarditis & Septic Pulmonary Emboli Right-sided staphylococcal endocarditis and multiple embolic pyogenic abscesses Petechial rash due to right-sided staph endocarditis Tricuspid valve endocarditis with Staphylococcus aureus , and multiple septic pulmonary emboli, prominent in the right upper lobe with both solid and cavitary appearance. Parasternal long axis view from a transthoracic echocardiogram. There is a small curvilinear vegetation on the mitral valve as indicated
    40. 40. Septicemia and Disseminated Infections (Other Than Endocarditis) <ul><li>Group A, ß-hemolytic , streptococcal septicemia (skin colonization) with high fever, toxicity, and renal failure from either septic thrombophlebitis or cellulitis </li></ul><ul><li>Candida parapsilosis has been isolated from street heroin containers and injection apparatus </li></ul><ul><li>Disseminated Candida albicans infection described in Europe during the 1980s had its source in the contaminated lemon juice used to dissolve the brown heroin </li></ul><ul><li>Aspergillus and mucormycotic [zygomycotic]) brain & renal abscesses (HIV) - Aspergillus has been detected in contaminated street heroin </li></ul><ul><li>Disseminated Rhodococcus equi infection, listeriosis , nocardiosis (pulmonary and brain abscess), relapsing Salmonella septicemia, and pyomyositis in intravenous drug users with advanced HIV infection </li></ul><ul><li>Pericarditis due to Bacillus cereus has been described in intravenous drug user with renal insufficiency on hemodialysis. Bacillus cereus spores were recovered from street heroin and his injection paraphernalia </li></ul>
    41. 41. Respiratory Tract Infections <ul><li>Drug users have increased incidence of bacterial pneumonia, especially that due to Haemophilus influenzae </li></ul><ul><li>Aspiration pneumonia as well as CAP pneumonia caused by S. pneumoniae , H. influenzae , S. aureus , and Klebsiella pneumoniae are among the most common reasons for hospitalization </li></ul><ul><li>Unusual organisms include Corynebacterium equi (now Rhodococcus equi ) and Nocardia </li></ul><ul><li>Undiagnosed HIV can first become evident as PCP pneumonia. </li></ul><ul><li>Septic pulmonary emboli produc in g pneumonias and lung abscesses in Tricuspid endocarditis </li></ul><ul><li>Tuberculosis with HIV in crack users - present in g with pneumonia atypically (i.e., without cavitary lesions), PPD negative. Only hilar or mediast in al lymphadenopathy </li></ul>
    42. 42. Non Infectious Pulmonary Complications <ul><li>Crack cociane inhalation causes focal air-space disease, atelectasis, alveolar hemorrhage, pneumothorax, pneumomediastinum, bronchiolitis obliterans, organizing pneumonia (BOOP), pulmonary infarction, and pulmonary edema. </li></ul><ul><li>Pulmonary edema - an important feature of heroin abuse and a major cause of death </li></ul><ul><li>Injecting insoluble additives or fillers ( talc and starch ) can produce chronic granulomatous inflammation and angiothrombosis and even delayed emphysema </li></ul><ul><li>“ Pocket shot&quot; - injection into the supraclavicular fossa in an attempt to hit the jugular, subclavian, or brachiocephalic veins can cause pneumo-hemothorax and pyopneumothorax, cellulitis, abscess, or a large hematoma forming a pseudoaneurysm </li></ul>
    43. 43. <ul><li>Cocaine induced eosinophilic lung disease </li></ul><ul><li>fever, bronchoconstriction, hypoxaemia, pulmonary infiltrates, and serum and bronchoalveolar lavage fluid eosinophilia after inhaling crack cocaine, resolved promptly after treatment with corticosteroids. </li></ul>Cocaine Lung Toxic oedema prsented as six month history of malaise and recently increasing haemoptysis       Pulmonary edema                   Pulmonary haemorrhage      Pulmonary barotrauma (Air escaping lungs by holding in crack smoke)         Foreign bodies in lungs       'Crack Lung' - Cough, shortness breath, fever, Talc in the lung Drug abuse. Injecting drugs (heroin, methamphetamine, cocaine...) that are frequently &quot;cut&quot; with talc will cause serious damage
    44. 44. Septicemia and Disseminated Infections
    45. 45. Clostridial infections <ul><li>A unique association exists between clostridial infections and the use of black-tar heroin , a form of heroin produced in Mexico </li></ul><ul><li>Botulism: Epidemic of wound botulism occurred in California dur in g the 1990s (Skin Popping) </li></ul><ul><li>Tetanus: (heroin skin popping) due to contamination of drugs with Clostridium tetani </li></ul><ul><li>C. sordellii : Necrotizing fasciitis with toxic shock syndrome </li></ul><ul><li>C. novyi and C. perfringens also causes soft-tissue infection in injection-drug users </li></ul>
    46. 46. Pulmonary and Cardiovascular Complications of IV Drug Use Charles E. Cherubin and Joseph D. Sapira
    47. 47. Gordon R and Lowy F. N Engl J Med 2005;353:1945-1954 Initial Management of Bacterial Infectious Syndromes among Suspected Drug Users
    48. 48. Syphilis and Other Sexually Transmitted Diseases <ul><li>Number of persons with syphilis is now increasing and the major component of this epidemiologic wave is the drug user </li></ul><ul><li>A substantial proportion of intravenous drug users are part of the HIV-infected population, the problems of diagnosis and treatment of syphilis are more complicated – (Seronegative secondary syphilis occurs in HIV-infected persons) </li></ul><ul><li>Gonorrhea, pelvic inflammatory disease, cervical dysplasia, chancroid, and nongonorrheal urethritis are also seen more frequently in the intravenous drug user </li></ul>
    49. 49. References <ul><li>Bacterial Infections in Drug Users Rachel J. Gordon, M.D., M.P.H., and Franklin D. Lowy, M.D. Volume 353:1945-1954 November 3, 2005 Number 18 </li></ul><ul><li>DEA Multimedia library. </li></ul><ul><li>National Drug Intelligence Center (NDIC) (www.usdoj.gov/ndic/pubs3/3843/images/photo1.jpg) </li></ul><ul><li>www.interpol.int/Public/Drugs/cocaine/image2.jpg </li></ul><ul><li>www.chp.ca.gov/dre/images/cocaine/cocaine4.gif </li></ul><ul><li>www.chp.ca.gov/dre/html/heroin.html </li></ul><ul><li>www.stopdrugs.org/images/heroin2.jpg </li></ul><ul><li>http://www.emedicine.com/emerg/topic164.htm#section~pictures </li></ul><ul><li>Injecting Drug Use: http://www.emedicine.com/med/topic586.htm </li></ul><ul><li>Thorax, Vol 47, 478-479, Copyright © 1992 by Thorax. </li></ul><ul><li>The Medical Complications of Drug Addiction and the Medical Assessment of the Intravenous Drug User: 25 Years Later , Charles E. Cherubin 15 November 1993 | Volume 119 Issue 10 | Pages 1017-1028 </li></ul>

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