Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.

Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia.

This research compared the long-term efficacy and safety of iloperidone with those of haloperidol in individuals with schizophrenia. Data were pooled from 3 prospective multicenter studies, each with 6-week stabilization followed by 46-week double-blind maintenance phases. Patients were randomized to iloperidone 4 to 16 mg/d or haloperidol 5 to 20 mg/d. Patients included in this analysis completed the initial 6-week phase with at least 20% reduction in Positive and Negative Syndrome Scale (PANSS) total score at weeks 4 and 6, had 7-item Clinical Global Impressions of Change (CGI-C) scores less than 4, received 1 or more doses of long-term phase medication, and had 1 or more efficacy/safety assessments during the long-term phase. The primary efficacy variable was time to relapse, defined as a 25% or more increase in PANSS total score, including at least a 10-point change; discontinuation because of lack of efficacy; aggravated psychosis with hospitalization; or 2-point increase in the 7-item CGI-C after week 6. Of 1644 patients randomized and 1326 completing the 6-week phase, 473 (iloperidone, n = 359; haloperidol, n = 114) were included in the long-term efficacy analysis, and 489 (iloperidone, n = 371; haloperidol, n = 118) in the safety analysis. Iloperidone was equivalent to haloperidol in time to relapse. The most common adverse events were insomnia (18.1%), anxiety (10.8%), and schizophrenia aggravated (8.9%) with iloperidone, and insomnia (16.9%), akathisia (14.4%), tremor (12.7%), and muscle rigidity (12.7%) with haloperidol. The Extrapyramidal Symptoms Rating Scale scores improved with iloperidone and worsened with haloperidol. Metabolic changes were minimal for both groups. Mean changes in Fridericia's QT interval correction were 10.3 msec (iloperidone) and 9.4 msec (haloperidol) at end point. Iloperidone demonstrated long-term efficacy equivalent to haloperidol and a favorable long-term safety profile, potentially making this agent a suitable option as maintenance therapy for schizophrenia.

Correlates of nonmedical use of hydromorphone and hydrocodone:results from a national household survey.

Over the past decade, the misuse and abuse of opioid medications in the United States has risen dramatically. Although data show a substantial variation in the nonmedical use of individual opioids, relatively little is known about risk factors for the nonmedical use of specific opioid products. This study compared the prevalence and correlates of the nonmedical use of oral immediate-release hydromorphone (marketed under the brand name of Dilaudid), versus that of hydrocodone combination products using a nationally representative sample of the civilian noninstitutionalized United States population aged 12 years or older. Data were from the 2003 National Survey on Drug Use and Health. An estimated 31.3 million individuals reported lifetime nonmedical use of an opioid analgesic. Of these, 2.9 percent reported lifetime nonmedical use of Dilaudid, and 51.9 percent reported lifetime nonmedical use of hydrocodone combination products exclusive of nonmedical Dilaudid use. Nonmedical Dilaudid users were likely to be older, Caucasian, and to have reported a higher lifetime prevalence of heroin, cocaine and injection drug use, as well as nonmedical use of other opioids. Nonmedical Dilaudid users were at higher risk for engaging in more serious substance abuse-related behaviors than those who reported lifetime nonmedical use of hydrocodone combination products.

UK smokers' and ex-smokers' reactions to cigarettes promising reduced risk.

AIMS: This study evaluated the impact of exposure to information about a novel cigarette claiming to reduce exposure to tobacco toxins ('potential reduced exposure product' cigarette or PREP-C) on smokers' and ex-smokers' perceptions of PREP-C, on quit interest among smokers and on interest in resuming smoking among ex-smokers. DESIGN AND PARTICIPANTS: A random digit-dialed telephone survey was conducted in the United Kingdom with 500 current smokers and 106 ex-smokers who had quit within the last 2 years. INTERVENTION: The interviewer described a novel cigarette that claimed to significantly reduce exposure to smoke toxins. MEASUREMENTS: Respondents' interest in purchasing the PREP-C, beliefs about its safety and risk reduction and smokers' quit interest, as measured by stage of change, before and after exposure to PREP-C information. FINDINGS: Among smokers, 76.5% were interested in purchasing PREP-C; interest did not vary by stage of change. Almost all smokers (90.6%) thought PREP-C was safer than regular cigarettes, with 5.4% indicating that the health risks were equivalent to not smoking at all. Exposure to PREP-C description did not change quit interest. Among ex-smokers, 5.6% believed PREP-C carried no health risk and 7.1% expressed purchase interest. CONCLUSIONS: Smokers and ex-smokers interpreted claims of reduced toxin exposure as reduced health risk and responded positively towards PREP-Cs. With the increasing introduction of PREP-Cs world-wide, evaluation of these products and their claims on quitting among smokers and on relapse among ex-smokers is a matter of public health urgency.

Non-medical use of OxyContin Tablets in the United States.

The non-medical use of OxyContin (controlled release oxycodone HCl) Tablets has been widely cited in media reports often leaving the impression that OxyContin was a source of primary or new onset drug abuse. However, no published research to date has examined the drug use history of those reporting non-medical use of OxyContin. This study examined rates of non-medical OxyContin use in the United States and the demographic and drug use profiles of those reporting such use, based on data from the 1999, 2000, and 2001 Substance Abuse and Mental Health Services Administration National Household Survey on Drug Abuse. Reported lifetime non-medical OxyContin use in the United States increased from 0.1% to 0.2% to 0.4% in 1999, 2000, and 2001 suggesting new incidence of 0.1%-0.2% per year. Compared to those reporting non-medical use of prescription analgesics other than OxyContin, non-medical OxyContin users were more likely to show a pattern of more serious drug abuse: they used multiple drugs, used needles for drug injection, and had higher rates of abuse and dependence. Approximately 83% of non-medical OxyContin users reported having used illicit drugs or other prescription medications non-medically prior to their first non-medical use of prescription analgesics. Even compared to those who reported non-medical use of other prescription analgesics, non-medical OxyContin users already had a more significant pattern of drug abuse before they began using prescription analgesics for non-medical purposes, suggesting that non-medical use of OxyContin is rarely the initiating factor leading to the abuse of other drugs.

The effectiveness of nicotine patch and nicotine lozenge in very heavy smokers.

The efficacy of nicotine replacement therapy (NRT) among very heavy and highly dependent smokers was examined in a secondary analysis of two randomized clinical trials of NRT. In the first trial, smokers were assigned to active patch (n=249) or placebo (n=253) plus intensive behavioral treatment. In the second trial, smokers were assigned to active 4-mg nicotine lozenge (n=450) or placebo (n=451) plus brief behavioral treatment. Nicotine patch and lozenge significantly increased 6-month continuous abstinence quit rates in both very heavy (>or=40 cigarettes per day) and highly dependent (Fagerström Tolerance Questionnaire or Fagerström Test for Nicotine Dependence score >7) smokers. The effect of active NRT treatment did not differ significantly by smoking rate or nicotine dependence, with the exception that the nicotine patch was significantly more effective than placebo in highly dependent smokers. The nicotine patch and lozenge are effective (vs. placebo) even in heavy and highly dependent smokers.

Patterns of over-the-counter nicotine gum use: persistent use and concurrent smoking.

AIMS: To examine the occurrence of persistent use (i.e. use beyond 12 weeks) and concurrent use of nicotine gum with cigarettes among consumers who purchase nicotine gum over-the-counter (OTC). DESIGN: Assessment of gum use was conducted in the context of a smoking cessation trial among smokers who purchased Nicorette gum and enrolled in the optional Committed Quitters smoking cessation program. Eligible participants were contacted by telephone 6 weeks and 12 weeks following their self-selected target quit date. Those who reported gum use at 12 weeks were contacted again at week 24. PARTICIPANTS: A total of 2655 current smokers who purchased nicotine gum and enrolled in a clinical efficacy trial of the Committed Quitters program. MEASUREMENTS: Detailed information on smoking and gum use, including frequency of use, amount used and reasons for use was obtained at each of the three follow-up assessments. FINDINGS: At the 24-week assessment, 6% of participants reported current use of nicotine gum (i.e. persistent use). Those engaging in persistent use averaged 4.7 (SD = 2.5) days of gum use per week and 3.2 (SD = 3.5) pieces of gum per day. Sixty-six per cent of persistent users reported at week 24 that they were not currently smoking, and 67% of persistent users reported they were using gum to establish or maintain abstinence. At the 6-, 12- and 24-week assessments, 14%, 10% and 2% of participants, respectively, reported current use of nicotine gum and current cigarette smoking (i.e. concurrent users). Those concurrent users reported at the 12-week follow-up that they did so an average of 4.4 (SD = 2.1) days per week, that they chewed an average of 2.6 (SD = 3.5) pieces of nicotine gum per day and that they smoked an average of 8.7 (SD = 8.6) cigarettes per day. CONCLUSION: Extended use of nicotine gum is rare. Concurrent use with cigarettes is uncommon. In both cases, the amount of gum use is small. OTC marketing of nicotine gum does not appear to have increased use contrary to labeling nor resulted in patterns of use that should warrant clinical or public health concerns.

Real-world efficacy of prescription and over-the-counter nicotine replacement therapy.

AIMS: To assess smoking cessation rates achieved with nicotine gum and patch in simulated over-the-counter (OTC) and actual prescription (Rx) settings. DESIGN: Separate open-label studies with gum and patch in OTC and Rx settings. PARTICIPANTS: There were multiple samples: OTC gum: 2981 smokers; OTC patch: 2367; Rx gum: 324; Rx patch: 669. INTERVENTIONS: All smokers received active nicotine replacement. In the OTC setting, smokers self-selected doses of nicotine gum (2 or 4 mg Nicorette) or patch (21, 14 or 7 mg NicoDerm CQ). No intervention was provided. In the Rx setting, smokers were prescribed gum or patch by their physician. MEASUREMENTS: Biochemically verified continuous smoking abstinence was assessed at 6 weeks (28-day abstinence) and 6 months. FINDINGS: OTC success rates were consistently higher than Rx rates: differences were significant at 6 weeks for both patch [OR = 1.45 (1.05-1.98)] and gum [OR 2.92 (1.58-5.40)], and remained significant at 6 months for patch [OR = 3.63: (1.74-7.61)] but not gum [OR = 1.37: (0.73-2.58)]. Among OTC gum users. 16.1% were abstinent at 6 weeks and 8.4% at 6 months. For Rx gum users, abstinence rates were 7.7% at 6 weeks and 7.7% at 6 months. With OTC patch, 19.0% were abstinent at 6 weeks and 9.2% at 6 months. With Rx patch. abstinence rates were 16.0% at 6 weeks and 3.0% at 6 months. CONCLUSIONS: Smoking cessation rates achieved with nicotine gum and patch under OTC conditions were as good as those under real-world prescribing conditions.