Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Fall rates in hospital rehabilitation units after individualised patient and staff education programmes: A pragmatic, stepped-wedge, cluster-randomised controlled trial

- Background Falls are the most frequent adverse events that are reported in hospitals. We examined the effectiveness of individualised falls-prevention education for patients, supported by training and feedback for staff, delivered as a ward-level programme. - Methods Eight rehabilitation units in general hospitals in Australia participated in this stepped-wedge, cluster-randomised study, undertaken during a 50 week period. Units were randomly assigned to intervention or control groups by use of computer-generated, random allocation sequences. We included patients admitted to the unit during the study with a Mini-Mental State Examination (MMSE) score of more than 23/30 to receive individualised education that was based on principles of changes in health behaviour from a trained health professional, in addition to usual care. We provided information about patients' goals, feedback about the ward environment, and perceived barriers to engagement in falls-prevention strategies to staff who were trained to support the uptake of strategies by patients. The coprimary outcome measures were patient rate of falls per 1000 patient-days and the proportion of patients who were fallers. All analyses were by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials registry, number ACTRN12612000877886). - Findings Between Jan 13, and Dec 27, 2013, 3606 patients were admitted to the eight units (n=1983 control period; n=1623 intervention period). There were fewer falls (n=196, 7·80/1000 patient-days vs n=380, 13·78/1000 patient-days, adjusted rate ratio 0·60 [robust 95% CI 0·42–0·94], p=0·003), injurious falls (n=66, 2·63/1000 patient-days vs 131, 4·75/1000 patient-days, 0·65 [robust 95% CI 0·42–0·88], p=0·006), and fallers (n=136 [8·38%] vs n=248 [12·51%] adjusted odds ratio 0·55 [robust 95% CI 0·38 to 0·81], p=0·003) in the intervention compared with the control group. There was no significant difference in length of stay (intervention median 11 days [IQR 7–19], control 10 days [6–18]). - Interpretation Individualised patient education programmes combined with training and feedback to staff added to usual care reduces the rates of falls and injurious falls in older patients in rehabilitation hospital-units.

Adherence to insulin treatment in diabetes: Can it be improved?

Insulin is used in all subjects with Type 1 diabetes, and when Type 2 diabetes is not controlled by oral anti-diabetic medicines, insulin is also used in Type 2 diabetes. However, despite this use, there is still increased mortality and morbidity in subjects with diabetes, compared to subjects without diabetes. One of the factors, which may be involved in this increased mortality and morbidity in subjects with diabetes, is nonadherence to insulin. Nonadherence rates to insulin are in the range20-38%, and many factors contribute to the nonadherence. The major aim of the review was to determine whether interventions to improve adherence to insulin do actually improve adherence to insulin. Most studies have shown that adherence to insulin was improved by changing from the vial-and-syringe approach to prefilled insulin pens, but not all studies have shown that this translated into better glycemic control and clinical outcomes. The results of studies using automatic telephone messages to improve adherence to insulin to date are inconclusive. There is limited and variable evidence that an intervention by a nurse/educator, which discusses adherence to medicines, does improve adherence to insulin. In contrast, there is little or no evidence that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. In conclusion, rather than assuming that an intervention by a health professional discussing adherence to insulin actually improves adherence to insulin, long-term studies investigating this are required.

A randomized controlled trial of a multiple health behavior change intervention delivered to colorectal cancer survivors: Effects on sedentary behavior

BACKGROUND Sedentary behavior may independently contribute to morbidity and mortality among survivors of colorectal cancer. In the current study, the authors assessed whether a telephone-delivered multiple health behavior change intervention had an effect on the sedentary behavior of recently diagnosed colorectal cancer survivors. METHODS A total of 410 participants were recruited through the Queensland Cancer Registry and randomized to the health coaching (intervention) or usual-care (control) group. Eleven health coaching sessions addressing multiple health behaviors, including sedentary behavior, were delivered over a period of 6 months. Data were collected at baseline (before randomization), at 6 months, and at 12 months via a telephone interview. RESULTS At 12 months, there was a significant decrease noted in the hours per day of sedentary time in both the health coaching (−1.21; 95% confidence interval [95% CI], −1.71 to −0.70) and usual-care groups (−0.55; 95% CI, −1.06 to −0.05), but the between-group difference was not found to be statistically significant (−0.65; 95% CI, −1.37 to 0.06 [P = .07]). In stratified subgroup analyses, the multiple health behavior change intervention was found to have a significant effect on total sedentary time (hours/day) at 12 months in survivors of colorectal cancer who were aged > 60 years (−0.90; 95% CI, −1.80 to −0.01 [P = .05]), male (−1.33; 95% CI, −2.44 to −0.21 [P = .02]), and nonobese (−1.10; 95% CI, −1.96 to −0.25; [P = .01]). CONCLUSIONS Incorporating simple messages about limiting sedentary behaviors into a multiple health behavior change intervention was found to have modest effects on sedentary behavior. A sedentary behavior-specific intervention strategy may be required to achieve substantial changes in sedentary behavior among colorectal cancer survivors

Efficacy and feasibility of a tele-health intervention for acute coronary syndrome patients with depression: Results of the 'MoodCare' randomized controlled trial

Background Depression is common after a cardiac event, yet there remain few approaches to management that are both effective and scalable. Purpose We aimed to evaluate the 6-month efficacy and feasibility of a tele-health program (MoodCare) that integrates depression management into a cardiovascular disease risk reduction program for acute coronary syndrome patients with low mood. Methods A two-arm, parallel, randomized design was used comprising 121 patients admitted to one of six hospitals for acute coronary syndrome. Results Significant treatment effects were observed for Patient Health Questionnaire 9 (PHQ9) depression (mean difference [change] = −1.8; p = 0.025; effect size: d = 0.36) for the overall sample, when compared with usual medical care. Results were more pronounced effects for those with a history of depression (mean difference [change] = −2.7; p = 0.043; effect size: d = 0.65). Conclusions MoodCare was effective for improving depression in acute coronary syndrome patients, producing effect sizes exceeding those of some face-to-face psychotherapeutic interventions and pharmacotherapy. (Trial Registration Number: ACTRN1260900038623.)

Dependence of light attenuation and backscattering on collagen concentration and chondrocyte density in agarose scaffolds

Optical coherence tomography (OCT) has been applied for high resolution imaging of articular cartilage. However, the contribution of individual structural elements of cartilage on OCT signal has not been thoroughly studied. We hypothesize that both collagen and chondrocytes, essential structural components of cartilage, act as important light scatterers and that variation in their concentrations can be detected by OCT through changes in backscattering and attenuation. To evaluate this hypothesis, we established a controlled model system using agarose scaffolds embedded with variable collagen concentrations and chondrocyte densities. Using OCT, we measured the backscattering coefficient (µb) and total attenuation coefficient (µt) in these scaffolds. Along our hypothesis, light backscattering and attenuation in agarose were dependent on collagen concentration and chondrocyte density. Significant correlations were found between µt and chondrocyte density (ρ = 0.853, p < 0.001) and between µt and collagen concentration (ρ = 0.694, p < 0.001). µb correlated significantly with chondrocyte density (ρ = 0.504, p < 0.001) but not with collagen concentration (ρ = 0.103, p = 0.422) of the scaffold. Thus, quantitation of light backscattering and, especially, attenuation could be valuable when evaluating the integrity of soft tissues, such as articular cartilage with OCT.

Charged-controlled separation of nitrogen from natural gas using boron nitride fullerene

Natural gas (the main component is methane) has been widely used as a fuel and raw material in industry. Removal of nitrogen (N2) from methane (CH4) can reduce the cost of natural gas transport and improve its efficiency. However, their extremely similar size increases the difficulty of separating N2 from CH4. In this study, we have performed a comprehensive investigation of N2 and CH4 adsorption on different charge states of boron nitride (BN) nanocage fullerene, B36N36, by using a density functional theory approach. The calculational results indicate that B36N36 in the negatively charged state has high selectivity in separating N2 from CH4. Moreover, once the extra electron is removed from the BN nanocage, the N2 will be released from the material. This study demonstrates that the B36N36 fullerene can be used as a highly selective and reusable material for the separation of N2 from CH4. The study also provides a clue to experimental design and application of BN nanomaterials for natural gas purification.

Numerical analysis of a new space-time variable fractional order advection-dispersion equation

Many physical processes appear to exhibit fractional order behavior that may vary with time and/or space. The continuum of order in the fractional calculus allows the order of the fractional operator to be considered as a variable. In this paper, we consider a new space–time variable fractional order advection–dispersion equation on a finite domain. The equation is obtained from the standard advection–dispersion equation by replacing the first-order time derivative by Coimbra’s variable fractional derivative of order α(x)∈(0,1]α(x)∈(0,1], and the first-order and second-order space derivatives by the Riemann–Liouville derivatives of order γ(x,t)∈(0,1]γ(x,t)∈(0,1] and β(x,t)∈(1,2]β(x,t)∈(1,2], respectively. We propose an implicit Euler approximation for the equation and investigate the stability and convergence of the approximation. Finally, numerical examples are provided to show that the implicit Euler approximation is computationally efficient.

The ovarian response to controlled stimulation in IVF cycles may be predictive of the age at menopause

STUDY QUESTION Can the number of oocytes retrieved in IVF cycles be predictive of the age at menopause? SUMMARY ANSWER The number of retrieved oocytes can be used as an indirect assessment of the extent of ovarian reserve to provide information on the duration of the reproductive life span in women of different ages. WHAT IS KNOWN ALREADY Menopause is determined by the exhaustion of the ovarian follicular pool. Ovarian reserve is the main factor influencing ovarian response in IVF cycles. As a consequence the response to ovarian stimulation with the administration of gonadotrophins in IVF treatment may be informative about the age at menopause. STUDY DESIGN, SIZE, DURATION In the present cross-sectional study, participants were 1585 infertile women from an IVF clinic and 2635 menopausal women from a more general population. PARTICIPANTS/MATERIALS, SETTING, METHODS For all infertile women, the response to ovarian stimulation with gonadotrophins was recorded. For menopausal women, relevant demographic characteristics were available for the analysis. MAIN RESULTS AND THE ROLE OF CHANCE A cubic function described the relationship between mean numbers of oocytes and age, with all terms being statistically significant. From the estimated residual distribution of the actual number of oocytes about this mean, a distribution of the age when there would be no oocytes retrieved following ovarian stimulation was derived. This was compared with the distribution of the age at menopause from the menopausal women, showing that menopause occurred about a year later. LIMITATIONS, REASONS FOR CAUTION The retrieved oocyte data were from infertile women, while the menopausal ages were from a more general population. WIDER IMPLICATIONS OF THE FINDINGS In the present study, we have shown some similarity between the distributions of the age when no retrieved oocytes can be expected after ovarian stimulation and the age at menopause. For a given age, the lower the ovarian reserve, the lower the number of retrieved oocytes would be and the earlier the age that menopause would occur.

Effects of a multiple health behavior change intervention for colorectal cancer survivors on psychosocial outcomes and quality of life: A randomized controlled trial

Background Multiple health behavior change can ameliorate adverse effects of cancer. Purpose The purpose of this study was to determine the effects of a multiple health behavior change intervention (CanChange) for colorectal cancer survivors on psychosocial outcomes and quality of life. Methods A total of 410 colorectal cancer survivors were randomized to a 6-month telephone-based health coaching intervention (11 sessions using acceptance and commitment therapy strategies focusing on physical activity, weight management, diet, alcohol, and smoking) or usual care. Posttraumatic growth, spirituality, acceptance, mindfulness, distress, and quality of life were assessed at baseline, 6 and 12 months. Results Significant intervention effects were observed for posttraumatic growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6 months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037). Conclusions The intervention improved psychosocial outcomes and quality of life (physical well-being) at 6 months with most effects still present at 12 months. (Trial Registration Number: ACTRN12608000399392).

Runs of homozygosity and a cluster of vulvar cancer in young Australian Aboriginal women

Objective A cluster of vulvar cancer exists in young Aboriginal women living in remote communities in Arnhem Land, Australia. A genetic case–control study was undertaken involving 30 cases of invasive vulvar cancer and its precursor lesion, high-grade vulvar intraepithelial neoplasia (VIN), and 61 controls, matched for age and community of residence. It was hypothesized that this small, isolated population may exhibit increased autozygosity, implicating recessive effects as a possible mechanism for increased susceptibility to vulvar cancer. Methods Genotyping data from saliva samples were used to identify runs of homozygosity (ROH) in order to calculate estimates of genome-wide homozygosity. Results No evidence of an effect of genome-wide homozygosity on vulvar cancer and VIN in East Arnhem women was found, nor was any individual ROH found to be significantly associated with case status. This study found further evidence supporting an association between previous diagnosis of CIN and diagnosis of vulvar cancer or VIN, but found no association with any other medical history variable. Conclusions These findings do not eliminate the possibility of genetic risk factors being involved in this cancer cluster, but rather suggest that alternative analytical strategies and genetic models should be explored.

Quality of life in children with Crohn disease

Objectives: Quality of life (QOL) is reportedly poor in children with Crohn disease (CD) but improves with increasing disease duration. This article aims to detail QOL in a cohort of Australian children with CD in relation to disease duration, disease activity, and treatment. MATERIALS AND METHODS: QOL, assessed using the IMPACT-III questionnaire, and disease activity measures, assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), were available in 41 children with CD. For this cohort, a total of 186 measurements of both parameters were available. Results: QOL was found to be significantly lower, and disease activity significantly higher (F = 31.1, P = 0.00), in patients within 6 months of their diagnosis compared with those up to 2.5 years, up to 5 years, and beyond 5 years since diagnosis. Higher disease activity was associated with poorer QOL (r =-0.51, P = 0.00). Total QOL was highest in children on nil medications and lowest in children on enteral nutrition. The PCDAI (t =-6.0, P = 0.00) was a significant predictor of QOL, with the clinical history (t =-6.9, P = 0.00) and examination (t =-2.9, P = 0.01) sections of the PCDAI significantly predicting QOL. Disease duration, age, or sex was neither related to nor significant predictors of QOL, but height z score and type of treatment approached significance. Conclusions: Children with CD within 6 months of their diagnosis have impaired QOL compared with those diagnosed beyond 6 months. These patients, along with those with growth impairment, ongoing elevated disease activity with abdominal pain, diarrhoea and/or perirectal and extraintestinal complications, may benefit from regular assessments of QOL as part of their clinical treatment. © 2010 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Comparison of the Cosmed K4 b2 and the Deltatrac II™ metabolic cart in measuring resting energy expenditure in adults

Background and Aims: The objective of the study was to compare data obtained from the Cosmed K4 b2 and the Deltatrac II™ metabolic cart for the purpose of determining the validity of the Cosmed K4 b2 in measuring resting energy expenditure. Methods: Nine adult subjects (four male, five female) were measured. Resting energy expenditure was measured in consecutive sessions using the Cosmed K4 b2, the Deltatrac II™ metabolic cart separately and the Cosmed K4 b2 and Deltatrac II™ metabolic cart simultaneously, performed in random order. Resting energy expenditure (REE) data from both devices were then compared with values obtained from predictive equations. Results: Bland and Altman analysis revealed a mean bias for the four variables, REE, respiratory quotient (RQ), VCO2, VO2 between data obtained from Cosmed K4 b2 and Deltatrac II™ metabolic cart of 268 ± 702 kcal/day, -0.0±0.2, 26.4±118.2 and 51.6±126.5 ml/min, respectively. Corresponding limits of agreement for the same four variables were all large. Also, Bland and Altman analysis revealed a larger mean bias between predicted REE and measured REE using Cosmed K4 b2 data (-194±603 kcal/day) than using Deltatrac™ metabolic cart data (73±197 kcal/day). Conclusions: Variability between the two devices was very high and a degree of measurement error was detected. Data from the Cosmed K4 b2 provided variable results on comparison with predicted values, thus, would seem an invalid device for measuring adults. © 2002 Elsevier Science Ltd. All rights reserved.

A controlled trial comparing the efficacy of rice-based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis

A prospective randomized trial was conducted to compare the efficacy of a rice-based oral rehydration solution (ORS) with glucose ORS in infants and children under 5 years of age with acute diarrhoea and mild to moderate dehydration (<10%). One hundred children presenting to a large metropolitan teaching hospital were eligible for entry to the study and were randomized to receive rice ORS or glucose ORS. Outcome measures were stool output (SO), duration of illness (DD) and recovery time to introduction of other fluids (RTF) and diet (RTD). Significant differences were found for all outcome measures in favour of the rice ORS group. Mean SO was lower (160 vs 213 mt; P<0.02), mean DD was reduced (17.3 vs 24.3 h; P = 0.03) and median RTF was decreased (12.7 vs 18.1 h; P< 0.001) in the rice ORS group compared with the glucose ORS group. The median rime to introduction of diet and mean length of hospital stay showed similar significant reductions. Our study has shown rice ORS to be an acceptable alternative to glucose ORS in young children and have shown that it is significantly more effective in reducing the course of diarrhoeal illness and the time taken to return to normal drinking and eating habits.

Low-temperature electrical conductivity of LaNi1-xFexO3

We report the electrical conductivity between 2 and 300 K for LaNi1-xFexO3 across the composition-controlled metal-insulator (m-i) transition. Using a method first suggested by Mobius, we identify the critical concentration x(c) to be 0.3 for the m-i transition. The negative temperature coefficient of resistivity observed at low temperatures in the metallic phase follows a temperature dependence characteristic of disorder effects. The semiconducting compositions (x greater than or equal to 0.3) do not show a simple activation energy but exhibit variable-range hopping at high temperatures confirming that the m-i transition in this system is driven by increasing disorder effects.