A re-focused and re-energised National Drugs Strategy, Issue 14, Summer 2005

The Mid-Term Review1 of the National Drugs Strategy 2001–2008, published on 2 June 2005, recommends a number of additions and amendments to the existing Strategy, including making rehabilitation a new, ‘fifth’ pillar of the Strategy. The Steering Group that oversaw the Review, and the extensive consultation process on which it is based, found that the aims and objectives of the Strategy are fundamentally sound. While what has been achieved varies from action to action, progress has been made across the four pillars of supply reduction, prevention, treatment and research, and in the co-ordination of the institutional structures of the Strategy. The Review recommends the addition of eight new actions, the replacement of nine of the existing actions and amendments to a further eight. It also recommends revisions to the Strategy’s key performance indicators, reflecting new developments and data availability. The recommendations serve to ‘re-focus and re-energise’ the Strategy in the remaining period up to 2008.This resource was contributed by The National Documentation Centre on Drug Use.

A brief cognitive behavioural intervention for regular amphetamine users. A treatment guide.

A brief intervention using motivational and cognitive behavioural approaches to help change drug use. Also offer alternative brief interventions for clients not suited to the current approach. This manual is divided into five sections: Section 1. Context Key points from the National Drug Strategy Monograph No 51. Models of Intervention and Care for Psychostimulant Users are included to present the evidence supporting this type of intervention for regular amphetamine users.  A flow-chart to place the intervention in a treatment context. Section 2. Brief background to the study and summary of results of evaluation A brief description of how the study was developed, undertaken and evaluated. A brief description of the evaluation outcome data (detailed results will be published separately). Section 3. The intervention The CBT intervention is presented in a clear and easy to use format for practitioners. Section 4. Suggested alternative brief interventions for those not suitable for the current intervention This section provides an overview of recommendations for alternative interventions for psychostimulant users who are unsuitable for the CBT intervention (e.g. those who are not considering change, experimental users etc). Section 5. Other available resources This section lists a range of other resources that are currently available for practitioners working with psychostimulant users. This treatment guide has not been designed to stand alone. Rather, practitioners are encouraged to: 1. Acquaint themselves with the current research and clinical literature. The recently completed monograph Models of Intervention and Care for Psychostimulant Users is an excellent resource for current evidence supporting practice in this area. 2. Undertake training in CBT and motivational enhancement techniques if unfamiliar with these approaches. 3. Obtain ongoing clinical supervision.This resource was contributed by The National Documentation Centre on Drug Use.

A Novel Pulse-Chase SILAC Strategy Measures Changes in Protein Decay and Synthesis Rates Induced by Perturbation of Proteostasis with an Hsp90 Inhibitor.

Standard proteomics methods allow the relative quantitation of levels of thousands of proteins in two or more samples. While such methods are invaluable for defining the variations in protein concentrations which follow the perturbation of a biological system, they do not offer information on the mechanisms underlying such changes. Expanding on previous work [1], we developed a pulse-chase (pc) variant of SILAC (stable isotope labeling by amino acids in cell culture). pcSILAC can quantitate in one experiment and for two conditions the relative levels of proteins newly synthesized in a given time as well as the relative levels of remaining preexisting proteins. We validated the method studying the drug-mediated inhibition of the Hsp90 molecular chaperone, which is known to lead to increased synthesis of stress response proteins as well as the increased decay of Hsp90 "clients". We showed that pcSILAC can give information on changes in global cellular proteostasis induced by treatment with the inhibitor, which are normally not captured by standard relative quantitation techniques. Furthermore, we have developed a mathematical model and computational framework that uses pcSILAC data to determine degradation constants kd and synthesis rates Vs for proteins in both control and drug-treated cells. The results show that Hsp90 inhibition induced a generalized slowdown of protein synthesis and an increase in protein decay. Treatment with the inhibitor also resulted in widespread protein-specific changes in relative synthesis rates, together with variations in protein decay rates. The latter were more restricted to individual proteins or protein families than the variations in synthesis. Our results establish pcSILAC as a viable workflow for the mechanistic dissection of changes in the proteome which follow perturbations. Data are available via ProteomeXchange with identifier PXD000538.

5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer

This work aimed to develop a new therapeutic approach to increase the efficacy of 5-fluorouracil (5-FU) in the treatment of advanced or recurrent colon cancer. 5-FU-loaded biodegradable poly(ε-caprolactone) nanoparticles (PCL NPs) were combined with the cytotoxic suicide gene E (combined therapy). The SW480 human cancer cell line was used to assay the combined therapeutic strategy. This cell line was established from a primary adenocarcinoma of the colon and is characterized by an intrinsically high resistance to apoptosis that correlates with its resistance to 5-FU. 5-FU was absorbed into the matrix of the PCL NPs during synthesis using the interfacial polymer disposition method. The antitumor activity of gene E from the phage ϕX174 was tested by generating a stable clone (SW480/12/E). In addition, the localization of E protein and its activity in mitochondria were analyzed. We found that the incorporation of 5-FU into PCL NPs (which show no cytotoxicity alone), significantly improved the drug's anticancer activity, reducing the proliferation rate of colon cancer cells by up to 40-fold when compared with the nonincorporated drug alone. Furthermore, E gene expression sensitized colon cancer cells to the cytotoxic action of the 5-FU-based nanomedicine. Our findings demonstrate that despite the inherent resistance of SW480 to apoptosis, E gene activity is mediated by an apoptotic phenomenon that includes modulation of caspase-9 and caspase-3 expression and intense mitochondrial damage. Finally, a strongly synergistic antiproliferative effect was observed in colon cancer cells when E gene expression was combined with the activity of the 5-FU-loaded PCL NPs, thereby indicating the potential therapeutic value of the combined therapy.

Indirect effects of peri-and postnatal choline treatment on place-learning abilities in rat.

This work was aimed at analyzing the effects of perinatal choline supplementation on the development of spatial abilities and upon adult performance. Choline supplementation (3.5 g/L in 0.02 M saccharin solution in tap water) was maintained for two weeks before birth and for up to four weeks postnatally. Additional supplementation was maintained from the fifth to the tenth week postnatally. Spatial-learning capacities were studied at the ages of 26, 65, or 80 days in a circular swimming pool (Morris place-navigation task) and at the age of 7 months in a homing arena. Treatment effects were found in both juvenile and adult rats, and thus persisted for several months after the cessation of the supplementation. The choline supplementation improved the performance in the water maze in a very selective manner. The most consistent effect was a reduction in the latency to reach a cued platform at a fixed position in space, whereas the improvement was limited when the platform was invisible and had to be located relative to distant cues only. However, after removal of the goal cue, the treated rats showed a better retention of the training position than did the control rats. A similar effect was observed in a dry-land task conducted in the homing arena. The choline supplementation thus induced a significant improvement of spatial memory. But since this effect was only evident following training with a salient cue, it might be regarded as an indirect effect promoted by an optimal combination of cue guidance with a place strategy.

Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus prophylaxis in kidney transplant recipients.

BACKGROUND.: We assessed the impact of a preemptive strategy after discontinuation of antiviral prophylaxis in the prevention of late-onset cytomegalovirus (CMV) disease in a cohort of kidney transplant recipients. METHODS.: Patients undergoing kidney transplantation at the University Hospital of Lausanne (CHUV) between November 2003 and November 2007 were included if they were donor or recipient (D/R) seropositive for CMV. All patients received 3 months of prophylaxis with valganciclovir, followed by monitoring of CMV DNAemia by polymerase chain reaction (PCR) every 15 days during 3 additional months. Valganciclovir was restarted if CMV PCR was more than or equal to 10,000 copies/mL. The primary endpoint of the study was the incidence of late-onset CMV disease. RESULTS.: Eighty-six kidney transplant recipients were included; 30 patients were D+/R- and 56 patients were R+ for CMV. At 6 months posttransplant, CMV DNAemia had occurred in 31 of 86 (36%) patients: 13 of 30 (43%) in the D+/R- group and 18 of 56 (32%) in the R+ group (P=0.35). In the D+/R- group, among the 13 patients with CMV DNAemia, 7 (54%) patients developed late-onset CMV disease, simultaneously to the first positive viral load (n=5) or after detection of low-grade viremia (n=2). Only two patients received a preemptive treatment. In the R+ group, all positive PCR results were below the established cutoff. Thus, these 18 patients were not treated, and none of them developed late-onset CMV disease (R+ vs. D+/R-: P<0.001). CONCLUSIONS.: Within the limitations of a noncontrolled study, our data indicate that a preemptive strategy after 3 months of valganciclovir prophylaxis for CMV is not useful in R+ kidney transplant recipients. In D+/R- patients, this approach should be further evaluated.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study.

BACKGROUND: Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. METHODS: A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999-2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. RESULTS: 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. CONCLUSIONS: A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result.

Ankle-Brachial Index: Nurses Strategy To Cardiovascular Disease Risk Factors Identification

Elevated risk of fatal and non-fatal cardiovascular events is associated with high prevalence of peripheral arterial disease, with assessment through the ankle-brachial index (ABI). This study aimed to demonstrate that the ABI and the Edinburgh Claudication Questionnaire are tools to be used by nurses in prevention and/or treatment of CVD (cardiovascular disease). A cross-sectional study was carried out with patients from a cardiovascular clinic. The Edinburgh Claudication Questionnaire was applied and the ABI was measured with the formula (ABI= Blood Pressure Ankle/Blood Pressure Brachial). A total of 115 patients were included, most were females (57.4%), aged 60.6 ± 12.5 years. The most prevalent risk factors were hypertension (64.3%), physical inactivity (48.7%) and family history (58.3%). The study showed that abnormal ABI was frequently found and 42.6% of the patients with abnormal ABI showed intermittent claudication. The method to evaluate the ABI associated to the Edinburg Claudication Questionnaire, can be easily used by nurses in the clinical evaluation of asymptomatic and symptomatic CVD patients.

Postoperative delirium. Part 2: detection, prevention and treatment.

To target pharmacological prevention, instruments giving an approximation of an individual patient's risk of developing postoperative delirium are available. In view of the variable clinical presentation, identifying patients in whom prophylaxis has failed (that is, who develop delirium) remains a challenge. Several bedside instruments are available for the routine ward and ICU setting. Several have been shown to have a high specificity and sensitivity when compared with the standard definitions according to DSM-IV-TR and ICD-10. The Confusion Assessment Method (CAM) and a version specifically developed for the intensive care setting (CAM-ICU) have emerged as a standard. However, alternatives allowing grading of the severity of delirium are also available. In many units, the approach to delirium follows a three-step strategy. Initially, non-pharmacological multicomponent strategies are used for primary prevention. As a second step, pharmacological prophylaxis may be added. Perioperative administration of haloperidol has been shown to reduce the severity, but not the incidence, of delirium. Perioperative administration of atypical antipsychotics has been shown to reduce the incidence of delirium in specific groups of patients. In patients with delirium, both symptomatic and causal treatment of delirium need to be considered. So far symptomatic treatment of delirium is primarily based on antipsychotics. Currently, cholinesterase inhibitors cannot be recommended and the data on dexmedetomidine are inconclusive. With the exception of alcohol-withdrawal delirium, there is no role for benzodiazepines in the treatment of delirium. It is unclear whether treating delirium prevents long-term sequelae.

Nursing performance in the policy transfer of directly observed treatment of tuberculosis

Objective Analyzing the policy transfer of directly observed treatment of tuberculosis from the perspective of nursing. Method This is a descriptive study with qualitative approach, which had 10 nurses of the Family Health Strategy in São Paulo as subjects. The interviews were carried out between May and June 2013, and were adopted the technique of thematic content analysis and the referential of policy transfer. Results On the signification of this treatment, are related the senses of disciplinary monitoring, the bond and approximation to the context of patients’ lives. Operationally, nurses, community health agents and nursing technicians stand out as agents of implementation of this policy, developing multiple actions of user embracement. The nurse is evidenced as an educator in health, leader in the family health team, and capable of creating emotional bond with users. Conclusion It was found that the innovations proposed in the treatment are incipient in the daily work of nurses.

Fenofibrate: a new treatment for diabetic retinopathy. Molecular mechanisms and future perspectives.

Despite improving standards of care, people with diabetes remain at risk of development and progression of diabetic retinopathy (DR) and visual impairment. Identifying novel therapeutic approaches, preferably targeting more than one pathogenic pathway in DR, and at an earlier stage of disease, is attractive. There is now consistent evidence from two major trials, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study and the Action to Control Cardiovascular Risk in Diabetes Eye (ACCORD-Eye) study, totalling 11,388 people with type 2 diabetes (5,701 treated with fenofibrate) that fenofibrate reduces the risk of development and progression of DR. Therefore, fenofibrate may be considered a preventive strategy for patients without DR or early intervention strategy for those with mild DR. A number of putative therapeutic mechanisms for fenofibrate, both dependent and independent of lipids, have been proposed. A deeper understanding of the mode of action of fenofibrate will further help to define how best to use fenofibrate clinically as an adjunct to current management of DR.

APPROACH AND TREATMENT OF SUICIDAL BEHAVIOR IN THE CLINICAL PRACTICE OF DIFFERENT GROUPS OF HEALTH PROFESSIONALS IN SPAIN: RESULTS OF THE PROJECT EUREGENA.

According to the WHO (World Health Organization) and the European Union, suicide is considered to be a health problem of prime importance and to be one of the principal causes of unnatural death. In Spain, the number of suicides has increased 12% since 2005 . The Research Project “European Regions Enforcing Actions against Suicide (EUREGENAS), funded by the Health Program 2008-2013, has as main objective the description of an integrated model of Mental Health orientated to the prevention of suicide. The differences that allow distinguishing the meaning of prevention in suicide behavior are described and explained through a qualitative methodological strategy and through the creation of discussion groups formed by different groups of health professionals. The results highlight the existing differences between the diverse health professionals who come more in contact with this problem and it shows as well the coincidence of meaning that suicide has to be considered as a priority in the field of health.

Iowa’s Drug Control Strategy, November 1, 2006

The attached annual report is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialists, law enforcement officers, a prevention specialist, a judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy were in developed in consultation with the DPAC.

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were euro60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (euro37,900/QALY gained), but not at F0-1 (euro103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

Iowa’s Drug Control Strategy, November 1, 2007

The attached annual report is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialists, law enforcement officers, a prevention specialist, a judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy were in developed in consultation with the DPAC.