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Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.
Abrha, S, Christenson, JK, McEwen, J, Tesfaye, W, Vaz Nery, S, Chang, AY, Spelman, T, Kosari, S, Kigen, G, Carroll, S, et al
BMJ open. 2021;(7):e047380
Abstract
INTRODUCTION Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.
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Role of vitamin D-calcium supplementation on metabolic profile and oxidative stress in gestational diabetes mellitus: A randomized controlled trial.
Gunasegaran, P, Tahmina, S, Daniel, M, Nanda, SK
The journal of obstetrics and gynaecology research. 2021;(3):1016-1022
Abstract
AIM: To assess role of vitamin D-calcium supplementation on the metabolic profile and oxidative stress in women with Gestational Diabetes Mellitus (GDM) controlled on diet. METHODS A randomized controlled trial was conducted at a tertiary care teaching hospital. Seventy women diagnosed as GDM at 24-28 weeks of gestation, controlled on a diabetic diet, were randomized to receive either vitamin D 1000 IU and calcium 1000 mg (group A, n = 34) or vitamin D 250 IU and calcium 500 mg (group B, n = 36) daily for 6 weeks. Levels of serum 25-hydroxy vitamin D, fasting plasma glucose (FPG), serum insulin, fasting lipid profile and total glutathione (GSH) were analyzed both prior to and after supplementation. Means, standard deviations and mean change were computed. Paired and independent t-tests were used to determine statistical significance between the two groups. RESULTS Women in group A showed a significant reduction in FPG level (P-value = 0.007), fasting serum insulin level (P-value = 0.000), LDL (P-value = 0.000), total cholesterol levels (P-value = 0.000) and increase in HDL levels (P-value = 0.000). Group B had a significant fall only in FPG after 6 weeks supplementation. A significant change in total glutathione level (P-value = 0.000) was observed in both groups. CONCLUSION Vitamin D and calcium supplementation at a dose of 1000 IU and 1000 mg, respectively, has a beneficial role in glucose metabolism, lipid metabolism and oxidative stress in GDM.
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Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial.
Wittert, G, Bracken, K, Robledo, KP, Grossmann, M, Yeap, BB, Handelsman, DJ, Stuckey, B, Conway, A, Inder, W, McLachlan, R, et al
The lancet. Diabetes & endocrinology. 2021;(1):32-45
Abstract
BACKGROUND Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme. METHODS T4DM was a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial done at six Australian tertiary care centres. Men aged 50-74 years, with a waist circumference of 95 cm or higher, a serum testosterone concentration of 14·0 nmol/L or lower but without pathological hypogonadism, and impaired glucose tolerance (oral glucose tolerance test [OGTT] 2-h glucose 7·8-11·0 mmol/L) or newly diagnosed type 2 diabetes (provided OGTT 2-h glucose ≤15·0 mmol/L) were enrolled in a lifestyle programme and randomly assigned (1:1) to receive an intramuscular injection of testosterone undecanoate (1000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years. Randomisation was done centrally, including stratification by centre, age group, waist circumference, 2-h OGTT glucose, smoking, and first-degree family history of type 2 diabetes. The primary outcomes at 2 years were type 2 diabetes (2-h OGTT glucose ≥11·1 mmol/L) and mean change from baseline in 2-h OGTT glucose, assessed by intention to treat. For safety assessment, we did a masked monitoring of haematocrit and prostate-specific antigen, and analysed prespecified serious adverse events. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000287831. FINDINGS Between Feb 5, 2013, and Feb 27, 2017, of 19 022 men who were pre-screened, 1007 (5%) were randomly assigned to the placebo (n=503) and testosterone (n=504) groups. At 2 years, 2-h glucose of 11·1 mmol/L or higher on OGTT was reported in 87 (21%) of 413 participants with available data in the placebo group and 55 (12%) of 443 participants in the testosterone group (relative risk 0·59, 95% CI 0·43 to 0·80; p=0·0007). The mean change from baseline 2-h glucose was -0·95 mmol/L (SD 2·78) in the placebo group and -1·70 mmol/L (SD 2·47) in the testosterone group (mean difference -0·75 mmol/L, -1·10 to -0·40; p<0·0001). The treatment effect was independent of baseline serum testosterone. A safety trigger for haematocrit greater than 54% occurred in six (1%) of 484 participants in the placebo group and 106 (22%) of 491 participants in the testosterone group, and a trigger for an increase of 0·75 μg/mL or more in prostate-specific antigen occurred in 87 (19%) of 468 participants in the placebo group and 109 (23%) of 480 participants in the testosterone group. Prespecified serious adverse events occurred in 37 (7·4%, 95% CI 5·4 to 10·0) of 503 patients in the placebo group and 55 (10·9%, 8·5 to 13·9) of 504 patients in the testosterone group. There were two deaths in each group. INTERPRETATION Testosterone treatment for 2 years reduced the proportion of participants with type 2 diabetes beyond the effects of a lifestyle programme. Increases in haematocrit might be treatment limiting. Longer-term durability, safety, and cardiovascular effects of the intervention remain to be further investigated. FUNDING Australian National Health and Medical Research Council, Bayer, Eli Lilly, University of Adelaide, and WW (formerly Weight Watchers).
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Associations between supermarket availability and body size in Australia: a cross-sectional observational study comparing state and territory capital cities.
Carroll, SJ, Turrell, G, Dale, MJ, Daniel, M
BMC public health. 2021;(1):407
Abstract
BACKGROUND Residential environment features such as availability of supermarkets may shape dietary behaviour and thus overweight and obesity. This relationship may not be consistent between cities. This Australian national-level study examined: 1) the relationship between supermarket availability and body size; and 2) whether this relationship varied by capital city. METHODS This study used 2017-18 Australian National Health Survey data including individual-level socio-demographic information (age, sex, country of birth, education, occupation, household income), and measured body size (height and weight to derive body mass index [BMI], and waist circumference [WC]). Objectively-expressed measures of residential environments included: counts of supermarkets (major chain outlets), counts of amenities (representing walkable destinations including essential services, recreation, and entertainment), and area of public open space - each expressed within road-network buffers at 1000 m and 1500 m; population density (1km2 grid cells); and neighbourhood disadvantage (Index of Relative Socioeconomic Disadvantage) expressed within Statistical Area Level 1 units. Data for adult respondents ≥18 years residing in each of Australia's state and territory capital cities (n = 9649) were used in multilevel models to estimate associations between supermarket availability and body size sequentially accounting for individual and other environment measures. An interaction term estimated city-specific differences in associations between supermarket availability and body size. Models were consequently repeated stratified by city. RESULTS Body size (BMI and WC) and supermarket availability varied between cities. Initial inverse associations between supermarket availability and body size (BMI and WC) were attenuated to null with inclusion of all covariates, except for BMI in the 1000 m buffer model (beta = - 0.148, 95%CI -0.27, - 0.01, p = 0.025). In stratified analyses, the strengths of associations varied between cities, remaining statistically significant only for some cities (BMI: Melbourne, Brisbane Hobart; WC: Brisbane, Hobart) in fully adjusted models. Different patterns of attenuation of associations with inclusion of covariates were evident for different cities. CONCLUSIONS For Australian capital cities, greater availability of supermarkets is associated with healthful body size. Marked between-city variations in body size, supermarket availability, and relationships between supermarket availability and body size do not, however, support universal, "one-size-fits-all" solutions to change built environments to support healthful body size.
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Associations between area socioeconomic status, individual mental health, physical activity, diet and change in cardiometabolic risk amongst a cohort of Australian adults: A longitudinal path analysis.
Carroll, SJ, Dale, MJ, Niyonsenga, T, Taylor, AW, Daniel, M
PloS one. 2020;(5):e0233793
Abstract
Presumed pathways from environments to cardiometabolic risk largely implicate health behaviour although mental health may play a role. Few studies assess relationships between these factors. This study estimated associations between area socioeconomic status (SES), mental health, diet, physical activity, and 10-year change in glycosylated haemoglobin (HbA1c), comparing two proposed path structures: 1) mental health and behaviour functioning as parallel mediators between area SES and HbA1c; and 2) a sequential structure where mental health influences behaviour and consequently HbA1c. Three waves (10 years) of population-based biomedical cohort data were spatially linked to census data based on participant residential address. Area SES was expressed at baseline using an established index (SEIFA-IEO). Individual behavioural and mental health information (Wave 2) included diet (fruit and vegetable servings per day), physical activity (meets/does not meet recommendations), and the mental health component score of the 36-item Short Form Health Survey. HbA1c was measured at each wave. Latent variable growth models with a structural equation modelling approach estimated associations within both parallel and sequential path structures. Models were adjusted for age, sex, employment status, marital status, education, and smoking. The sequential path model best fit the data. HbA1c worsened over time. Greater area SES was statistically significantly associated with greater fruit intake, meeting physical activity recommendations, and had a protective effect against increasing HbA1c directly and indirectly through physical activity behaviour. Positive mental health was statistically significantly associated with greater fruit and vegetable intakes and was indirectly protective against increasing HbA1c through physical activity. Greater SES was protective against increasing HbA1c. This relationship was partially mediated by physical activity but not diet. A protective effect of mental health was exerted through physical activity. Public health interventions should ensure individuals residing in low SES areas, and those with poorer mental health are supported in meeting physical activity recommendations.
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Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1 versus placebo as a prophylaxis for recurrence urinary tract infections in children: a study protocol for a randomised controlled trial.
Daniel, M, Szymanik-Grzelak, H, Turczyn, A, Pańczyk-Tomaszewska, M
BMC urology. 2020;(1):168
Abstract
BACKGROUND Urinary tract infections (UTIs) are one of the most common bacterial infections in children. In children < 7 years of age, the prevalence of one episode of symptomatic UTI has been estimated at 3-7% in girls and 1-2% in boys, whereas 8-30% of them will have one or more episodes of UTI. The use of some probiotics appears to reduce the risk of recurrence of UTIs. Since the effects of probiotics are strain-specific, the efficacy and safety of each strain has to be assessed. The main aim of this study is to determine whether probiotics (containing Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1) therapy are effective in preventing UTI in children compared to placebo. METHOD A superiority, double-blind, randomised, controlled trial is being conducted. One hundred and six patients aged 3 to 18 years with recurrent UTIs in last year (defined as: ≥ 2 episodes of UTI with acute pyelonephritis/upper UTI; or 1 episode of UTI with acute pyelonephritis and ≥ 1 episodes of UTI with cystitis/lower UTI; or ≥ 3 episodes of UTI with cystitis/lower UTI) or children with ≥ 1 infection in the upper urinary tract and ≥ 1 of recurrent UTIs risk factors (congenital anomalies of the kidney and urinary tract, constipation, bladder dysfunction, myelomeningocele, sexual activity in girls) will be randomly assigned to receive a 90-day prophylaxis arm (probiotic containing L. rhamnosus PL1 and L. plantarum PM1) or a 90-day placebo arm. The primary outcome measure will be the frequency of recurrence of UTI during the intervention and in the period 9 months after the intervention. DISCUSSION The findings of this randomised controlled trial (RCT), whether positive or negative, will contribute to the formulation of further recommendations on prevention of recurrent UTIs in children. TRIAL REGISTRATION NUMBER NCT03462160, date of trial registration 12th March 2018.
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Examining adherence to activity monitoring devices to improve physical activity in adults with cardiovascular disease: A systematic review.
Marin, TS, Kourbelis, C, Foote, J, Newman, P, Brown, A, Daniel, M, Coffee, NT, Nicholls, SJ, Ganesan, A, Versace, VL, et al
European journal of preventive cardiology. 2019;(4):382-397
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Abstract
BACKGROUND Activity monitoring devices are currently being used to facilitate and monitor physical activity. No prior review has examined adherence to the use of activity monitoring devices amongst adults with cardiovascular disease. METHODS Literature from June 2012 to October 2017 was evaluated to examine the extent of adherence to any activity monitoring device used to collect objective physical activity data. Randomized control trials comparing usual care against the use of an activity monitoring device, in a community intervention for adults from any cardiovascular diagnostic group, were included. A systematic search of databases and clinical trials registers was conducted using Joanna Briggs Institute methodology. RESULTS Of 10 eligible studies, two studies reported pedometer use and eight accelerometer use. Six studies addressed the primary outcome. Mean adherence was 59.1% (range 39.6% to 85.7%) at last follow-up. Studies lacked equal representation by gender (28.6% female) and age (range 42 to 82 years). CONCLUSION This review indicates that current research on activity monitoring devices may be overstated due to the variability in adherence. Results showed that physical activity tracking in women and in young adults have been understudied.
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A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial.
Hall, DA, Ray, J, Watson, J, Sharman, A, Hutchison, J, Harris, P, Daniel, M, Millar, B, Large, CH
Hearing research. 2019;:153-166
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Abstract
AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.
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Local descriptive body weight and dietary norms, food availability, and 10-year change in glycosylated haemoglobin in an Australian population-based biomedical cohort.
Carroll, SJ, Paquet, C, Howard, NJ, Coffee, NT, Adams, RJ, Taylor, AW, Niyonsenga, T, Daniel, M
BMC public health. 2017;(1):149
Abstract
BACKGROUND Individual-level health outcomes are shaped by environmental risk conditions. Norms figure prominently in socio-behavioural theories yet spatial variations in health-related norms have rarely been investigated as environmental risk conditions. This study assessed: 1) the contributions of local descriptive norms for overweight/obesity and dietary behaviour to 10-year change in glycosylated haemoglobin (HbA1c), accounting for food resource availability; and 2) whether associations between local descriptive norms and HbA1c were moderated by food resource availability. METHODS HbA1c, representing cardiometabolic risk, was measured three times over 10 years for a population-based biomedical cohort of adults in Adelaide, South Australia. Residential environmental exposures were defined using 1600 m participant-centred road-network buffers. Local descriptive norms for overweight/obesity and insufficient fruit intake (proportion of residents with BMI ≥ 25 kg/m2 [n = 1890] or fruit intake of <2 serves/day [n = 1945], respectively) were aggregated from responses to a separate geocoded population survey. Fast-food and healthful food resource availability (counts) were extracted from a retail database. Separate sets of multilevel models included different predictors, one local descriptive norm and either fast-food or healthful food resource availability, with area-level education and individual-level covariates (age, sex, employment status, education, marital status, and smoking status). Interactions between local descriptive norms and food resource availability were tested. RESULTS HbA1c concentration rose over time. Local descriptive norms for overweight/obesity and insufficient fruit intake predicted greater rates of increase in HbA1c. Neither fast-food nor healthful food resource availability were associated with change in HbA1c. Greater healthful food resource availability reduced the rate of increase in HbA1c concentration attributed to the overweight/obesity norm. CONCLUSIONS Local descriptive health-related norms, not food resource availability, predicted 10-year change in HbA1c. Null findings for food resource availability may reflect a sufficiency or minimum threshold level of resources such that availability poses no barrier to obtaining healthful or unhealthful foods for this region. However, the influence of local descriptive norms varied according to food resource availability in effects on HbA1c. Local descriptive health-related norms have received little attention thus far but are important influences on individual cardiometabolic risk. Further research is needed to explore how local descriptive norms contribute to chronic disease risk and outcomes.
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Detailed methods of two home-based vegetable gardening intervention trials to improve diet, physical activity, and quality of life in two different populations of cancer survivors.
Cases, MG, Frugé, AD, De Los Santos, JF, Locher, JL, Cantor, AB, Smith, KP, Glover, TA, Cohen, HJ, Daniel, M, Morrow, CD, et al
Contemporary clinical trials. 2016;:201-12
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BACKGROUND Cancer survivors suffer from long-term adverse effects that reduce health-related quality of life (QOL) and physical functioning, creating an urgent need to develop effective, durable, and disseminable interventions. Harvest for Health, a home-based vegetable gardening intervention, holds promise for these domains. METHODS This report describes the methods and recruitment experiences from two randomized controlled feasibility trials that employ a waitlist-controlled design. Delivered in partnership with Cooperative Extension Master Gardeners, this intervention provides one-on-one mentorship of cancer survivors in planning and maintaining three seasonal vegetable gardens over 12months. The primary aim is to determine intervention feasibility and acceptability; secondary aims are to explore effects on objective and subjective measures of diet, physical activity and function, and QOL and examine participant factors associated with potential effects. One trial is conducted exclusively among 82 female breast cancer survivors residing in the Birmingham, AL metropolitan area (BBCS); another broadly throughout Alabama among 46 older cancer survivors aged >60 (ASCS). RESULTS Response rates were 32.6% (BBCS) and 52.3% (ASCS). Both trials exceeded 80% of their accrual target. Leading reasons for ineligibility were removal of >10 lymph nodes (lymphedema risk factor), lack of physician approval, and unwillingness to be randomized to the waitlist. CONCLUSION To date, recruitment and implementation of Harvest for Health appears feasible. DISCUSSION Although both studies encountered recruitment challenges, lessons learned can inform future larger-scale studies. Vegetable gardening interventions are of interest to cancer survivors and may provide opportunities to gain life skills leading to improvements in overall health and QOL.