***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND The extent of prescription opioid abuse has led to the development of formulations that are difficult to crush . The purpose of the present studies was to examine whether experienced prescription opioid abusers ( individuals using prescription opioids for non-medical purpose s regardless of how they were obtained ) were able to prepare a formulation of oxymorphone hydrochloride ER 40 mg design ed to be crush-resistant ( DCR ) for intranasal ( study 1 ) or intravenous abuse ( study 2 ) , utilizing a non-crush-resistant formulation of oxymorphone ( 40 mg ; OXM ) as a positive control . METHODS No drug was administered in these studies . Participants were provided with DCR and OXM tablets in r and om order and asked to prepare them for abuse with tools/solutions that they had previously requested . The primary outcome for study 1 was particle size distribution , and the primary outcome for study 2 was percent yield of active drug in the extracts . Other descriptive variables were examined to better underst and potential responses to these formulations . RESULTS Fewer DCR than OXM particles were smaller than 1.705 mm ( 9.8 % vs. 97.7 % ) , and thus appropriate for analyses . Percent yield of active drug in extract was low and did not differ between the two formulations ( DCR : 1.95 % ; OXM : 1.29 % ) . Most participants were not willing to snort ( 92 % ) or inject ( 84 % ) the tampered products . Participants indicated that they found less relative value in the DCR than the OXM formulation across both studies . CONCLUSIONS These data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse UNLABELLED ALO-01 ( EMBEDA [ morphine sulfate and naltrexone hydrochloride ] extended-release capsules [ King Pharmaceuticals , Inc , Bridgewater , NJ ] ) , indicated for chronic moderate-to-severe pain , is design ed to release naltrexone upon tampering ( eg , by crushing ) , reducing morphine-induced subjective effects . This multicenter , r and omized , double-blind , crossover study assessed pharmacokinetics , efficacy , and safety of ALO-01 and compared them with extended-release morphine sulfate ( ERMS , KADIAN [ morphine sulfate extended-release ] capsules [ Actavis US , Morristown , NJ ] ) in adults ( N = 113 ) with osteoarthritis pain . Study periods included washout until pain flare ( intensity > or = 5 , 0 to 10 ; 0 = no pain , 10 = worst pain ) ; dose titration with ERMS ( 20 to 160 mg BID ) ; and r and omization to 2 ( crossover ) 14-day treatment periods with ERMS or ALO-01 , separated by 7 days of open-label ERMS . Assessment s included pharmacokinetics ( morphine , naltrexone ) , pain scores ( 0 to 10 ) , Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index ; Patient Global Assessment of Medication ( 1 to 5 ; poor to excellent ) . Mean score at pain flare was 7.1 . Morphine exposure from both formulations at steady state was similar . Plasma naltrexone concentrations were below limit-of-quantification for most patients and , when present , did not impact pain scores . During treatment , mean pain intensity ( day 14 : ERMS , 2.4 ; ALO-01 , 2.3 , P = .31 ) , WOMAC change-from-baseline ( mean pain , physical function , composite scores ) , and adverse event frequency were similar . ALO-01 and ERMS provided similar relief of  osteoarthritis pain . PERSPECTIVE We present data demonstrating that ALO-01 has steady-state morphine exposure , efficacy , and safety similar to marketed ERMS capsules . Results highlight the potential for morphine in ALO-01 to manage moderate-to-severe osteoarthritis pain , while the sequestered naltrexone does not interfere with efficacy BACKGROUND Sublingual buprenorphine is an effective maintenance treatment for opioid dependence , yet intravenous buprenorphine misuse occurs . A buprenorphine/naloxone formulation was developed to mitigate this misuse risk . This r and omized , double-blind , cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users ( IDUs ) . METHODS Intravenous heroin users ( n = 12 ) lived in the hospital for 8 - 9 weeks and were maintained on each of three  different sublingual buprenorphine doses  ( 2 mg , 8 mg , 24 mg ) . Under each maintenance dose , participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo , naloxone , heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined . Every participant received each test dose under the three buprenorphine maintenance dose conditions . RESULTS Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin ( P < 0.0005 ) . Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose . Subjective ratings of ' drug liking ' and ' desire to take the drug again ' were lower for buprenorphine/naloxone than for buprenorphine or heroin ( P = 0.0001 ) . Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin ( P < 0.05 ) . Seven adverse events were reported ; most were mild and transient . CONCLUSIONS These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential , that potential is lower than it is for buprenorphine alone , particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses . Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment Assessment s of personality disorder ( PD ) and conduct disorder ( CD ) in a r and om community sample at mean age 13 were employed to predict  subsequent substance abuse disorder ( SUD ) , trajectories of symptoms of abuse or dependence on alcohol , marijuana  , or other illicit substances , and hazard of initiating marijuana use  over the subsequent decade . Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks , participant sex , and other Axis I disorders . Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms . For several models the greatest of these effects were shown for borderline PD and for conduct disorder , the predecessor of adult antisocial PD . Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana . Analyses over 30 years suggest that Cluster B PD ( borderline , histrionic , narcissistic ) are independent risks for development of SUD and warrant clinical attention Abstract Background : Opioid analgesics can be abused by crushing followed by solubilization and intravenous injection to attain rapid absorption . Morphine sulfate and naltrexone hydrochloride extended release capsules ( EMBEDA ® , MS-sNT ) , indicated for management of chronic , moderate to severe pain , contain pellets of morphine sulfate with a sequestered naltrexone core . Should product tampering by crushing occur , the sequestered naltrexone is intended for release to reduce morphine-induced subjective effects . Objective : This study compared self-reports of high , euphoria , and drug-liking effects of intravenous morphine alone versus intravenous morphine combined with naltrexone in a clinical simulation of intravenous abuse of crushed MS-sNT . Methods : This single-center , r and omized , double-blind , crossover study characterized subjective effects of naltrexone administered intravenously at the same ratio to morphine present in MS-sNT . Subjects were male and had used prescription opioids five or more times within the previous 12 months to get ‘ high ’ but were not physically dependent on opioids . The primary outcome was the response to the Drug Effects Question naire ( DEQ ) question # 5 , “ How high are you now ? ” ( 100 mm Visual Analog Scale [ VAS ] ) . The secondary outcome was the response to a Cole/Addiction Research Center Inventory ( ARCI ) Stimulation-Euphoria modified scale . Additional outcomes included resonse to VAS drug liking , the remaining DEQ questions , and pupillometry . Results : Administration of intravenous naltrexone following intravenous morphine diminished mean high ( 29.8 vs 85.2 mm ) , Cole/ARCI Stimulation-Euphoria ( 13.7 vs 27.8 mm ) , and drug-liking ( 38.9 vs 81.4 mm ) scores ( all p < 0.0001 ) compared with intravenous morphine alone . No serious adverse events occurred as a result of the tested ratio of naltrexone to morphine . Conclusions : Results in this study population suggest that naltrexone added to morphine in the 4 % ratio within MS-sNT mitigates the high , euphoria , and drug liking of morphine alone , potentially reducing the attractiveness for product tampering . Assessment of the true clinical significance of these findings will require further study Background Evaluation of tamper resistant formulations ( TRFs ) and classwide Risk Evaluation and Mitigation Strategies ( REMS ) for prescription opioid analgesics will require baseline descriptions of abuse patterns of existing opioid analgesics , including the relative risk of abuse of existing prescription opioids and characteristic patterns of abuse by alternate routes of administration ( ROAs ) . This article presents , for one population at high risk for abuse of prescription opioids , the unadjusted relative risk of abuse of hydrocodone , immediate release ( IR ) and extended release ( ER ) oxycodone , methadone , IR and ER morphine , hydromorphone , IR and ER fentanyl , IR and ER oxymorphone . How relative risks change when adjusted for prescription volume of the products was examined along with patterns of abuse via ROAs for the products . Methods Using data on prescription opioid abuse and ROAs used from 2009 Addiction Severity Index-Multimedia Version ( ASI-MV ® ) Connect assessment s of 59,792 patients entering treatment for substance use disorders at 464 treatment facilities in 34 states and prescription volume data from SDI Health LLC , unadjusted and adjusted risk for abuse were estimated using log-binomial regression models . A r and om effects binary logistic regression model estimated the predicted probabilities of abusing a product by one of five ROAs , intended ROA ( i.e. , swallowing whole ) , snorting , injection , chewing , and other . Results Unadjusted relative risk of abuse for the 11 compound/formulations determined hydrocodone and IR oxycodone to be most highly abused while IR oxymorphone and IR fentanyl were least often abused . Adjusting for prescription volume suggested hydrocodone and IR oxycodone were least often abused on a prescription-by-prescription basis . Methadone and morphine , especially IR morphine , showed increases in relative risk of abuse . Examination of the data without methadone revealed ER oxycodone as the drug with greatest risk after adjusting for prescription volume . Specific ROA patterns were identified for the compounds/formulations , with morphine and hydromorphone most likely to be injected . Conclusions Unadjusted risks observed here were consistent with rankings of prescription opioid abuse obtained by others using different population s/ methods . Adjusted risk estimates suggest that some , less widely prescribed analgesics are more often abused than prescription volume would predict . The compounds/formulations investigated evidence d unique ROA patterns . Baseline abuse patterns will be important for future evaluations of TRFs and REMS Many persons seeking opiate treatment  present with complex clinical challenges , which may be exacerbated by alcohol misuse . This report details secondary data analyses aggregating treatment-seeking sample s across 10 National Institute on Drug Abuse ( NIDA ) Clinical Trials Network treatment trials to examine alcohol-related characteristics of  opiate- primary ( OP ) clients and compare broad pretreatment characteristics of those with and without an alcohol use disorder ( AUD ) . Analysis of this aggregate OP client sample ( n = 1,396 ) indicated that 38 % had comorbid AUD and that a history of alcohol treatment episodes and recent alcohol problems were common . Further , comparisons of OP clients with and without AUD revealed the former were more likely to have had a history of pervasive difficulties in psychosocial functioning . Findings suggest the need for detection of and intervention for alcohol misuse at the outset of opiate treatment and support for the practice of availing medical , psychological , case management , and other support services BACKGROUND Opioids are used extensively for chronic pain management in the United States . The frequency of opioid use prior to presenting to interventional pain management setting s and in interventional pain management setting s has been shown to be above 90 % . Given that controlled substance abuse and illicit drug use are prevalent phenomena , adherence monitoring of patients that are prescribed opioids is becoming common . Adherence monitoring is carried out by an appropriate history , periodic evaluation of appropriate intake of dru 
    Output:
    
Weak to moderate evidence supports the value of thorough patient assessment , risk-screening tools , controlled-substance agreements , careful dose titration , opioid dose ceilings , compliance monitoring , and adherence to practice guidelines .
Moderate to strong evidence suggests that prescribing tamper-resistant opioids may help prevent misuse but may also have the unintended consequence of prompting a migration of users to other marketed opioids , heroin , or other substances .
Similarly , preliminary evidence suggests that although recent regulatory and legal efforts may reduce misuse , they also impose barriers to the legitimate treatment of pain .