Toward third-generation aptamers: Spiegelmers and their therapeutic prospects

Single-stranded mirror-image oligonucleotides, which are highly resistant to nuclease degradation and are capable of tightly and specifically binding to protein targets to inhibit their function, have been developed as potential therapeutic agents. The scientific discoveries that led to the development of the Spiegelmer technology are described in this review, along with recent preclinical developments of the first therapeutic Spiegelmers.     

Drug-free therapeutic community: a ten-year follow-up

Two previous follow-ups of 50 patients at the Veterans Administration Medical Center, Brentwood Division, West Los Angeles, Residential Treatment Center (RTC), were conducted in 1974 and 1981. This is a 10-year follow-up of the same cohorts conducted in 1984. We were able to locate 11 out of 50 candidates. Of the 11 candidates located, interviews were completed on six candidates. Of the remaining five patients, two are decreased and the other three were unable to be interviewed. Of the six patients that were interviewed, three were drug-free since treatment; one has been drug-free for the last five years. The other two patients had been drug-free approximately six months. It would appear that follow-up studies of this particular group of subjects are very difficult and that the outcome of treatment is difficult to evaluate due to difficulty in locating this group of subjects over a long term.     

Ceftriaxone: a third-generation cephalosporin

Ceftriaxone is a new third-generation cephalosporin with excellent activity against many gram-negative, and reasonable activity against most gram-positive microorganisms. Clinical studies have demonstrated its efficacy and safety in patients with bacterial meningitis; respiratory tract, urinary tract, soft tissue, bone and joint infections; and gonorrhea. Ceftriaxone has been well tolerated except for diarrhea, which in most cases has not required a change in therapy. The long elimination half-life of ceftriaxone has allowed twice- and once-daily administration, the latter potentially resulting in substantial cost savings. Because of its documented efficacy, safety, and convenient dosing schedule, ceftriaxone may become the preferred third-generation cephalosporin for the treatment of a variety of serious infections.     

Relapse precipitants in addictions:results in a therapeutic community

In this paper, a study examining high-risk situations for relapse is presented. The sample consisted of 72 participants (51 male and 21 female) who had relapsed after having received a residential psychological treatment for drug addition in a therapeutic community in Spain. In order to analyze what personal, environmental or social factors were the most immediate triggers of relapse, a personal interview, using the Relapse Interview, was administered to each one of the relapsed patients. Results showed that most of the relapses took place during the first year after completing the treatment program. Likewise, the factors most frequently cited for relapse were the following: to cope with negative emotional states (49.5%), to be unable to resist temptations or impulses to consume (17.5%), to test personal control (10.3%) and to cope with interpersonal conflicts (9.3%). Results indicate thatmost factors were of an intrapersonal nature. Implications of these results for further research and clinical practice are commented upon.     

Beta-adrenoceptor antagonists in elderly patients with chronic heart failure: therapeutic potential of third-generation agents

Chronic heart failure (CHF) is a common and disabling condition with an incidence and prevalence that increase sharply with age. The median age of presentation of new heart failure cases is > 75 years. Effective treatments, including beta-adrenoceptor antagonists, have been proven in randomised, controlled trials. The average age in these placebo-controlled mortality and morbidity studies of beta-adrenoceptor antagonists in heart failure has, however, been < 63 years, and all patients with an ejection fraction > or = 40% were excluded. This lack of a representative sample of elderly patients with heart failure has raised concerns about extrapolating the available evidence for beta-adrenoceptor antagonists to a more elderly heart failure population. Beta-adrenoceptor antagonists may have a less beneficial effect or even an adverse effect in elderly heart failure patients. There is evidence that beta-adrenoceptor antagonists are less frequently prescribed in elderly CHF patients, and that this lack of treatment is associated with impaired outcomes. Establishing which beta-adrenoceptor antagonists, if any, are effective in elderly CHF is therefore of extreme importance. The elderly have a reduced cardiovascular reserve and may be less tolerant of the introduction of a vasoconstricting beta-adrenoceptor antagonist. In addition, the higher proportion of elderly CHF patients with relatively preserved systolic function (for which no treatment has been proven to reduce mortality and morbidity) means that we cannot say with certainty that beta-adrenoceptor antagonists have been proven to be effective in a general elderly CHF population. Third-generation beta-adrenoceptor antagonists with vasodilating actions in addition to their beta-adrenoceptor antagonist effects may offer several theoretical advantages over earlier beta-adrenoceptor antagonists for elderly CHF patients. Three of this class (carvedilol, bucindolol and nebivolol) have been evaluated with respect to their efficacy in reducing mortality and morbidity in CHF, and only two of these (carvedilol and nebivolol) had a proven outcome benefit in a properly powered randomised, controlled trial. Only the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (which used the vasodilating third-generation beta-adrenoceptor antagonist nebivolol) has prospectively investigated the treatment of CHF in elderly patients, including those with preserved systolic function, and demonstrated a significant reduction in the risk of death or cardiovascular hospitalisation. In conclusion, prescribers are advised that nebivolol should be preferred in elderly patients with CHF, because of its proven efficacy in a representative group of elderly CHF patients.     

Marathon therapy: treating rape survivors in a therapeutic community.

Odyssey House is a therapeutic community (TC) in New York City that treats a wide range of drug abusers. For over 20 years. Odyssey House has conducted an annual marathon therapy group for women who are rape survivors. This article summarizes the program's experience with the marathon and reports on its therapeutic accomplishments.     

Nebivolol: third-generation beta-blockade

Nebivolol is a third generation beta-blocker. It is highly selective for the beta1-adrenoceptor, and has additional nitric oxide-mediated vasodilating and antioxidant properties, along with a favourable metabolic profile. Nebivolol is well tolerated by patients with hypertension and heart failure. Although several smaller studies were conducted with nebivolol in hypertensive patients, no large randomised clinical trials have been performed to prove efficacy on hard clinical end points. In patients with heart failure, a large mortality/morbidity trial was conducted, and nebivolol was shown to reduce the composite end point of mortality and hospitalisations. Nebivolol is registered, in Europe, for mild-to-moderate, uncomplicated hypertension and mild-to-moderate heart failure; and outside Europe, for hypertension. This review describes experimental and clinical data regarding this selective beta-blocker with vasodilating and antioxidant effects.     

Comprehensive therapeutic interchange program in a community hospital

The implementation of a comprehensive therapeutic interchange program is described. The need to reduce the number of telephone calls to physicians about nonformulary drug orders, reduce drug costs, and maximize the effectiveness of drug therapy prompted the development of an automatic therapeutic interchange program at a 273-bed nonteaching community hospital. Pharmacists and physicians agreed that a telephone call to discuss every nonformulary drug order was unnecessary. The pharmacy department presented the automatic interchange program to the pharmacy and therapeutics committee. The program was reviewed by the committee, the hospital attorney, and medical staff members and was instituted in 1986 for drug products, such as vitamins and antacids, for which interchanges are noncontroversial. A newsletter describing the program was distributed, and inservice education sessions were held. A reminder was placed on order forms that an interchange for nonformulary drugs would be made unless the nonformulary agent was deemed "medically necessary" by the physician. In such cases, the physician is contacted to discuss the therapeutic alternative. As acceptance of the program and cost efficiencies were demonstrated, more controversial agents were phased in during subsequent years. It was difficult to obtain approval to add some agents, such as third-generation cephalosporins, to the program, but noncompliance and confusion have been minimal. An automatic therapeutic interchange program has worked well at this institution since 1986.     

Modified therapeutic community for co-occurring disorders: a summary of four studies

This article summarizes results from four research studies (n = 902) that examined the effectiveness of the modified therapeutic community (MTC) for clients with co-occurring disorders (most with severe mental disorders). Significantly better outcomes for MTC were found across four experimental versus control comparisons on 23.1% (12 of 52) of primary outcome measures of substance use, mental health, crime, HIV risk, employment, and housing. Study limitations included the potential for selection bias, limited measurement of program fidelity, and insufficient examination of the relationship between treatment dose and outcome. Future research should emphasize clinical trial replications, multiple outcome domains, and further development of continuing care models. Given the need for research-based approaches, the MTC warrants consideration when program and policy planners are designing programs for co-occurring disorders.     

Evaluation of a therapeutic community treatment program: a long-term follow-up study in Spain

The aims of this study is to carry out a long-term follow-up evaluation of a well-established therapeutic community treatment for addictions in Navarre (Spain) and to make a comparison between the program completers and the dropouts, as well as between relapsing and nonrelapsing patients, on a broad set of variables. A long-term follow-up design (mean of 6 years after leaving treatment) was used to analyze the outcomes of the therapeutic program. The sample consisted of 155 subjects (113 completers and 42 dropouts). A personal interview was carried out with each one of the located subjects. The interviews took place between September 2000 and September 2004. Treatment "dropouts" manifested a higher and earlier rate both of relapses, and of new treatments for their drug addiction than the completion group. The program was also effective in reducing criminal behavior and improving the state of health. Significant differences were found across outcome variables when comparison was made between treatment completers and "dropouts." All subjects improved on outcome variables after receiving the treatment. When relapsing and nonrelapsing patients were compared, significant outcome differences were also found between groups. The study's limitations are noted and future needed research is suggested.     

The experience of drug-dependent adolescents in a therapeutic community

Introduction and Aims. Drug treatment programs for adolescents are now more widespread with some evidence of success. However, there has been little in‐depth exploration of factors that may encourage or hinder program completion. This ethnographic study of an adolescent therapeutic community aimed to provide insights into the experience of the adolescent residents. Design and Methods. Four months of participant observation at a program for drug‐dependent adolescents in a metropolitan city in Australia. Twenty‐one residents (15 boys and six girls) aged between 14 and 18 years participated, comprising all residents admitted during the study period. Results. Vocational Education and Art Therapy are activities that universally engaged residents whereas frustration was evident in Journaling—a core program activity. Group sessions were often used to set up or dismantle social cliques, although they were also useful to expose difficult inter‐personal relationships. The risk of residents ‘taking off’ was heightened during breaks from program activities when strong emotions surfaced. Discussion and Conclusions. There needs to be a more central role for creative and vocational activities in adolescent programs and a variety of ways for them to document their journey. Group encounters need to be skilfully facilitated by staff to handle fluid inter‐personal dynamics and residents need support outside of formal program time to minimise drop‐out. The concept of a navigation‐engagement continuum is discussed and the need to see treatment as a series of encounters that may be ‘successful’ despite ‘non‐completion’. This study gives adolescents a voice in program evaluation which may help improve retention.[Foster M, Nathan S, Ferry M. The experience of drug‐dependent adolescents in a therapeutic community. Drug Alcohol Rev 2010;29;531–539]     

Personality assessment of substance-dependent patients in a therapeutic community

The design and implementation of a personality assessment system for severely substance-dependent men in a therapeutic community (TC) are described. The system was designed from a treatment utility perspective (Hayes, Nelson, & Jarrett, 1987) and uses the Personality Research Form E (Jackson, 1984) to provide each patient with feedback (a) describing his normal personality traits, (b) predicting his probable pattern of adjustment to the treatment setting, and (c) prescribing specific actions he can take to address potentially problematic behaviors. Discussing the results with the patient helps him cope with the TC. Reviewing the assessment results with the staff promotes their empathy for the patient as a person whose behavior can be understood as an interaction of his personality with the specific demands of the TC rather than seeing the patient in exclusively pathological terms. Specific suggestions for behavior change guide both the patient and the staff and are potentially useful in various treatment settings.