Joining forces - Combining cognition-targeted motor control training with group or individual pain physiology education: A successful treatment for chronic low back pain

Chronic unremittent low back pain (LBP) is characterised by cognitive barriers to treatment. Combining a motor control training approach with individualised education about pain physiology is effective in this group of patients. This randomized comparative trial (i) evaluates an approach to motor control acquisition and training that considers the complexities of the relationship between pain and motor output, and (ii) compares the efficacy and cost of individualized and group pain physiology education. After an "ongoing usual treatment" period, patients participated in a 4-week motor control and pain physiology education program. Patients received four one-hour individualized education sessions (IE) or one 4-hour group lecture (GE). Both groups reduced pain (numerical rating scale) and disability (Roland Morris Disability Questionnaire). IE showed bigger decreases, which were maintained at 12 months (P < 0.05 for all). The combined motor control and education approach is effective. Although group education imparts a lesser effect, it may be more cost-efficient. [ABSTRACT FROM AUTHOR]

Using a problem detection study (PDS) to identify and compare health care provider and consumer views of antihypertensive therapy

The objectives of this study were to ascertain consumer knowledge and behaviour about hypertension and treatment and to compare these with health care providers' perceptions (of 'most' consumers). The design for the study was a problem detection study (PDS): focus groups and then survey. Focus groups and survey participants were convenience samples of consumers, doctors, nurses and pharmacists. The main outcome measures were agreement on a 5-point Likert scale with statements about consumers' knowledge and behaviour about high blood pressure and medication. The survey identified areas of consensus and disagreement between consumers and health providers. While general knowledge and concordance with antihypertensive therapy among consumers was good, consequences such as eye and kidney disease, interactions with herbal medicines, and how to deal with missing a dose were less well known. Side effects were a problem for over one-quarter of participants, and cost was a problem in continuing therapy. Half the consumers had not received sufficient written information. Providers overall disagreed that most consumers have an adequate understanding of the condition. They agreed that most consumers adhere to therapy and can manage medicines; and about their own profession's role in information provision and condition management. Consumers confirmed positive provider behaviour, suggesting opportunities for greater communication between providers about actions taken with their consumers. In conclusion, the PDS methodology was useful in identifying consumer opinions. Differences between consumer and provider responses were marked, with consumers generally rating their knowledge and behaviour above providers' ratings of 'most' consumers. There are clear gaps to be targeted to improve the outcomes of hypertension therapy.

Is vaccine therapy the future in cancer prevention?

One vaccine designed to prevent cancer by preventing a precursor infection is already in common use, and at least one more is in the latter stages of clinical development. These vaccines are part of a new era of cancer immunoprophylaxis. Several further vaccines are in preclinical and clinical development, targeted at preventing cancer precursor infections, and these should add to our ability to prevent this common human disorder. However, vaccines to prevent cancers not triggered by infection are a more remote prospect, for a variety of reasons.

Evaluating Patient Education Materials about Radiation Therapy

Targeted treatment education for cancer patients has the potential to promote adjustment through assisting patients to participate in treatment decision making, comply with treatment regimens and cope more effectively with treatment side effects. A quasi-experimental longitudinal pre-test post-test and follow-up design was used to assess the effect of a patient education video about radiation therapy on patients' psychological distress, knowledge about radiation therapy, self-efficacy about coping with treatment and physical symptoms. Patients with head and neck (n = 26) and breast cancer (n = 66) were recruited into the study and allocated into control and intervention groups. No significant differences were found between the control and intervention groups on any of the outcome variables. However, patients in the intervention group reported high levels of satisfaction with the video and all reported that they would recommend the video to other patients preparing for radiation therapy. As well, 90% of patients in the intervention group reported that some or all of the information in the video was new to them. Education materials that have excellent face validity and that are well received by patients may fail to produce significant change using standard controlled study designs. Future research in this area may need to consider alternative paradigms for evaluating the helpfulness of such materials. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Conjugation of an antibody to cross-linked fibrin for targeted delivery of anti-restenotic drugs

There is an urgent need to treat restenosis, a major complication of the treatment of arteries blocked by atherosclerotic plaque, using local delivery techniques. We observed that cross-linked fibrin (XLF) is deposited at the site of surgical injury of arteries. An antibody to XLF, conjugated to anti-restenotic agents, should deliver the drugs directly and only to the site of injury. An anti-XLF antibody (H93.7C.1D2/48; 1D2) was conjugated to heparin (using N-succinimidyl 3-(2-pyridyldithio)-propionate), low molecular weight heparin (LMWH) (adipic acid dihydrazide) and rapamycin (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide), and the conjugates purified and tested for activity before use in vivo. Rabbits had their right carotid arteries de-endothelialised and then given a bolus of 1D2-heparin, 1D2-LMWH or 1D2-rapamycin conjugate or controls of saline, heparin, LMWH, rapamycin or 1D2 (+/-heparin bolus) and sacrificed after 2 or 4 weeks (12 groups, n=6/group). Rabbits given any of the conjugates had minimal neointimal development in injured arteries, with up to 59% fewer neointimal cells than those given control drugs. Rabbits given 1D2-heparin or 1D2-LMWH had an increased or insignificant reduction in luminal area, with positive remodelling, while the medial and total arterial areas of rabbits given 1D2-rapamycin were not affected by injury. Arteries exposed to 1D2-heparin or 1D2-rapamycin had more endothelial cells than rabbits given control drugs. Thus, XLF-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall, where the conjugates can influence remodelling, re-endothelialisation and neointimal cell density, with reduced neointimal formation. (C) 2004 Elsevier B.V. All rights reserved.

Targeted delivery of heparin and LMWH using a fibrin antibody prevents restenosis

This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dinner (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 mug/k,g 1D2-heparin (26-70 mug/kg heparin) or 1D2-LMWH (29-80 mug/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 mug/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Genetic and economic analysis of a targeted marker-assisted wheat breeding strategy

The advent of molecular markers as a tool to aid selection has provided plant breeders with the opportunity to rapidly deliver superior genetic solutions to problems in agricultural production systems. However, a major constraint to the implementation of marker-assisted selection (MAS) in pragmatic breeding programs in the past has been the perceived high relative cost of MAS compared to conventional phenotypic selection. In this paper, computer simulation was used to design a genetically effective and economically efficient marker-assisted breeding strategy aimed at a specific outcome. Under investigation was a strategy involving the integration of both restricted backcrossing and doubled haploid (DH) technology. The point at which molecular markers are applied in a selection strategy can be critical to the effectiveness and cost efficiency of that strategy. The application of molecular markers was considered at three phases in the strategy: allele enrichment in the BC1F1 population, gene selection at the haploid stage and the selection for recurrent parent background of DHs prior to field testing. Overall, incorporating MAS at all three stages was the most effective, in terms of delivering a high frequency of desired outcomes and at combining the selected favourable rust resistance, end use quality and grain yield alleles. However, when costs were included in the model the combination of MAS at the BC1F1 and haploid stage was identified as the optimal strategy. A detailed economic analysis showed that incorporation of marker selection at these two stages not only increased genetic gain over the phenotypic alternative but actually reduced the over all cost by 40%.

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

Objective: Antidepressant drugs and cognitive-behavioural therapy (CBT) are effective treatment options for depression and are recommended by clinical practice guidelines. As part of the Assessing Cost-effectiveness - Mental Health project we evaluate the available evidence on costs and benefits of CBT and drugs in the episodic and maintenance treatment of major depression. Method: The cost-effectiveness is modelled from a health-care perspective as the cost per disability-adjusted life year. Interventions are targeted at people with major depression who currently seek care but receive non-evidence based treatment. Uncertainty in model inputs is tested using Monte Carlo simulation methods. Results: All interventions for major depression examined have a favourable incremental cost-effectiveness ratio under Australian health service conditions. Bibliotherapy, group CBT, individual CBT by a psychologist on a public salary and tricyclic antidepressants (TCAs) are very cost-effective treatment options falling below $A10 000 per disability-adjusted life year (DALY) even when taking the upper limit of the uncertainty interval into account. Maintenance treatment with selective serotonin re-uptake inhibitors (SSRIs) is the most expensive option (ranging from $A17 000 to $A20 000 per DALY) but still well below $A50 000, which is considered the affordable threshold. Conclusions: A range of cost-effective interventions for episodes of major depression exists and is currently underutilized. Maintenance treatment strategies are required to significantly reduce the burden of depression, but the cost of long-term drug treatment for the large number of depressed people is high if SSRIs are the drug of choice. Key policy issues with regard to expanded provision of CBT concern the availability of suitably trained providers and the funding mechanisms for therapy in primary care.

Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite 150 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families ( 931 from an Australian group and 245 from a U. K. group), each with at least two members-mainly affected sister pairs-with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 ( maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 MLS p 2.09). Minor peaks with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.

Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Synthesis and immunological evaluation of M protein targeted tetra-valent and tri-valent group A streptococcal vaccine candidates based on the lipid-core peptide system

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However. if left untreated. these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, Particularly in developing countries and in indigenous populations of affluent countries. Only ever occur following GAS infection, a vaccine offers Promise for their Prevention. As stich, we have investigated the Use of the lipid-core peptide (LCP) system for the development of multi-valent Prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant LIP to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems Were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.

Cautionary tales in the interpretation of systematic reviews of therapy trials

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.