Emerging host cell targets for hepatitis C therapy

Chronic hepatitis C virus (HCV) infection is a major burden on humanity. The current HCV therapy has limited efficacy, and there is pressing need for new and more effective therapies. Host cell factors that are required for HCV infection, replication and/or pathogenesis represent potential therapeutic targets. Of particular interest are cellular receptors that mediate HCV entry, factors that facilitate HCV replication and assembly, and intracellular pathways involving lipid biosynthesis, oxidative stress and innate immune response. A crucial challenge now is to manipulate such cellular targets pharmacologically for chronic HCV treatment, without being limited by side effects.

Hormone therapy is associated with smaller achilles tendon diameter in active post-menopausal women

The effects of hormonal status and activity levels on Achilles tendon structure were examined in asymptomatic post-menopausal women. It was hypothesized that women using hormone replacement therapy (HRT) would have better tendon structure than those not using HRT and that active women would have poorer tendon structure than inactive women. Eighty-five women including 53 active women (regular golf players) and 32 controls (healthy but inactive women) recorded their HRT and menopausal history and underwent basic anthropometric measurements. Women were divided into two groups based on their hormonal status: those currently using HRT; and those who had never used HRT or ceased using HRT at least 12 months prior to the study. Achilles tendons were examined with ultrasound and categorized as normal or abnormal, and the diameter of each tendon (mm) was recorded. Active women had a greater prevalence of tendon abnormality ( P=0.10) and thicker Achilles tendons than inactive women ( P<0.05). Active women on HRT had less tendon abnormality ( P=0.056) than active women not on HRT and significantly less tendon thickness ( P<0.05). This study indicates that Achilles tendon diameter is greater in active post-menopausal women. Hormone replacement therapy appeared to ameliorate this effect in active women. A similar effect from HRT on the Achilles tendons of inactive women was not apparent.

Fine motor difficulties: the need for advocating for the role of occupational therapy in schools

Background: Fine motor difficulties can impact on the academic, social and emotional development of a student. Aim: The aims of this paper are to: (i) investigate the need for support to students experiencing fine motor  difficulties from the perspective of their classroom teachers, and (ii) report on the level of knowledge teachers have in regard to the role of occupational therapists in supporting students with fine motor difficulties.  Methods: Fifteen teachers from a stratified random sample of public schools within two regions of Victoria, Australia, were interviewed in this qualitative, grounded theory investigation. Results: Results showed that the current level of support for students with fine motor difficulties is inadequate. Conclusion: Occupational therapists in Victoria need to advocate their role in developing the fine motor skills of students at both an organisational and an individual level in order to increase the access of students with fine motor difficulties to occupational therapy services.

Relationship of glutathione S-transferase genotypes with side-effects of pulsed cyclophsphamide therapy in patients with systemic lupus erythematosus

Aims
Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.
Methods
DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile→Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay.
Results
Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients.
Conclusions
The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.

Preliminary study of the effect of low-intensity home-based physical therapy in chronic stroke patients

This study was a preliminary examination of the effect of low-intensity home-based physical therapy on the performance of activities of daily living (ADL) and motor function in patients more than 1 year after stroke. Twenty patients were recruited from a community stroke register in Nan-Tou County, Taiwan, to a randomized, crossover trial comparing intervention by a physical therapist immediately after entry into the trial (Group I) or after a delay of 10 weeks (Group II). The intervention consisted of home-based physical therapy once a week for 10 weeks. The Barthel Index (BI) and Stroke Rehabilitation Assessment of Movement (STREAM) were used as standard measures for ADL and motor function. At the first follow-up assessment at 11 weeks, Group I showed greater improvement in lower limb motor function than Group II. At the second follow-up assessment at 22 weeks, Group II showed improvement while Group I had declined. At 22 weeks, the motor function of upper limbs, mobility, and ADL performance in Group II had improved slightly more than in Group I, but the between-group differences were not significant. It appears that low-intensity home-based physical therapy can improve lower limb motor function in chronic stroke survivors. Further studies will be needed to confirm these findings.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective:
To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to ‘current practice’.
Method:
The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria (‘equity’; ‘strength of evidence’, ‘feasibility’ and ‘acceptability to stakeholders’) is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6–17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios.
Results:
Compared to current practice, CBT by public psychologists is the most costeffective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders.
Conclusions:
Cognitive behavioural therapy provided by a public psychologist is the most
effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require ‘start-up’ costs and attention to ensuring an adequate workforce.

Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease

Background & Aims: Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn’s disease. We report a prospective, parallel, placebo-controlled, double-blind, randomized trial of 2 years of clarithromycin, rifabutin, and clofazimine in active Crohn’s disease, with a further year of follow-up. Methods: Two hundred thirteen patients were randomized to clarithromycin 750 mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in addition to a 16-week tapering course of prednisolone. Those in remission (Crohn’s Disease Activity Index ≤150) at week 16 continued their study medications in the maintenance phase of the trial. Primary end points were the proportion of patients experiencing at least 1 relapse at 12, 24, and 36 months. Results: At week 16, there were significantly more subjects in remission in the antibiotic arm (66%) than the placebo arm (50%; P = .02). Of 122 subjects entering the maintenance phase, 39% taking antibiotics experienced at least 1 relapse between weeks 16 and 52, compared with 56% taking placebo (P = .054). At week 104, the figures were 26% and 43%, respectively (P = .14). During the following year, 59% of the antibiotic group and 50% of the placebo group relapsed (P = .54). Conclusions: Using combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for up to 2 years, we did not find evidence of a sustained benefit. This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn’s disease in the majority of patients. Short-term improvement was seen when this combination was added to corticosteroids, most likely because of nonspecific antibacterial effects.

Hormone replacement therapy and cardiovascular disease

The authors examine the most recent research concerning the risks and benefits of oestrogen or combined oestrogen-progestin therapy in postmenopausal women.

A review of play and play assessment used in occupational therapy

In occupational therapy play is regarded as important in itself. This view has been influenced by occupational science and the assumption that play is a child's primary occupation. To reflect this change in the view of play, assessments of play are now being developed which focus on aspects of behaviour which are unique to play. As a result of this work on play, play training programs have been developed which focus on teaching children how to play.

Low-flow oxygen therapy: selecting the right device

The authors provide and overview of oxygen therapy principles, describing the indications and care requirements of three low flow oxygen therapy devices and providing an algorithm for managing refractory hypoxaemia.