J L Bowden

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

The magnitude and rate of reduction in strength, dexterity and sensation in the human hand vary with ageing

Cutaneous sensation and motor performance of the hand decline with age. It is not known if motor performance declines are influenced by reductions in cutaneous sensation, or if motor performance deteriorates at a consistent rate across motor tasks. Handgrip strength, finger-tapping frequency and grooved-pegboard performance were assessed for both hands of 70 subjects (20-88 years), 10 per decade. Motor declines were compared to reductions in perceptual cutaneous sensation tested at 10 hand sites using calibrated von Frey filaments. Motor performance decreased with age for all motor tasks (p<0.001). Handgrip strength (mean±SEM) decreased from 42.6±9.5 kg (in the 30s), to 23.7±7.6 kg (80s) or 44%; finger-tapping frequency from 6.4±0.8 Hz to 4.2±0.9 Hz, 34%; and grooved-pegboard (median [IQR]) increased from 59 s [57-66 s] to 111.5 s [101-125 s], 47%. The onset of the deterioration in motor performance varied with sex and task. Cutaneous sensation also decreased with age, measured as increased von Frey thresholds of 0.04 g [0.02-0.07] to 0.16 g [0.04-0.4] (p<0.001) between the 20s and the 80s, or 73%. Cutaneous sensation varied with sex, side-tested and site. Reductions in grip-based tasks were associated with sensory declines in the palm, but elsewhere there was little correlation among motor tasks and cutaneous sensation in the hand. Grooved-pegboard performance was the best predictor of age-related declines in motor performance regardless of sex or side-tested. Our results suggest age-related declines in motor function cannot be inferred from, or provide information about, changes in cutaneous sensation.

Electrical stimulation plus progressive resistance training for leg strength in spinal cord injury: A randomized controlled trial

Study design:A randomized controlled trial.Objectives:To determine the effectiveness of electrical stimulation (ES)-evoked muscle contractions superimposed on progressive resistance training (PRT) for increasing voluntary strength in the quadriceps muscles of people with spinal cord injuries (SCI).Setting:Sydney, Australia.Methods:A total of 20 people with established SCI and neurologically induced weakness of the quadriceps muscles participated in the trial. Participants were randomized between experimental and control groups. Volunteers in the experimental group received ES superimposed on PRT to the quadriceps muscles of one leg thrice weekly for 8 weeks. Participants in the control group received no intervention. Assessments occurred at the beginning and at the end of the 8-week period. The four primary outcomes were voluntary strength (Nm) and endurance (fatigue ratio) as well as the performance and satisfaction items of the Canadian Occupational Performance Measure (COPM; points).Results:The between-group mean differences (95% confidence interval (CI)) for voluntary strength and endurance were 14 Nm (1–27; P=0.034) and 0.1 (−0.1 to 0.3; P=0.221), respectively. The between-group median differences (95% CI) for the performance and satisfaction items of the COPM were 1.7 points (−0.2 to 3.2; P=0.103) and 1.4 points (−0.1 to 4.6; P=0.058), respectively.Conclusion:ES superimposed on PRT improves voluntary strength, although there is uncertainty about whether the size of the treatment effect is clinically important. The relative effectiveness of ES and PRT is yet to be determined.

The effectiveness of 22 commonly administered physiotherapy interventions for people with spinal cord injury: a systematic review

Study design:A systematic review of randomised controlled trials.Objectives:To determine the effectiveness of 22 commonly administered physiotherapy interventions for people with spinal cord injuries (SCIs).Methods:The inclusion criteria contained 22 pairs of key interventions and outcomes. Each intervention and outcome was considered independently such that 22 brief reviews were conducted and summarised in this one paper. The interventions included hand, wheelchair, seated mobility, fitness, strength and gait training, as well as electrical stimulation, passive movements, stretch, cycling, exercise and transcutaneous electrical nerve stimulation (TENS). Interventions were compared with no or sham treatment, usual care or another physiotherapy intervention. The primary outcome for each review was one of the following: seated mobility, wheelchair mobility, hand function, gait, voluntary strength, joint mobility, fitness and pain. Data were extracted to determine mean between-group differences or risk ratios (95% confidence interval). Where possible, results were pooled in meta-analyses and the strength of evidence rated using Grading of Recommendations Assessment, Development and Evaluation.Results:Thirty-eight randomised controlled trials met the inclusion criteria and were relevant to 15 of the brief reviews. The following four interventions were clearly effective: fitness, hand and wheelchair training as well as TENS; however, the strength of evidence was not high for any of these interventions. None of the other interventions were clearly effective.Conclusion:There is initial evidence to support four physiotherapy interventions, but there is still a long way to go to put a strong evidence base to the range of physiotherapy interventions commonly used to manage people with SCI.

Voluntary Activation is Reduced in Both the More- and Less-Affected Upper Limbs after Unilateral Stroke

Objective: Measurement of voluntary activation gives an indication of neural drive to the muscle. This study aimed to identify the site of impairment in neural drive during voluntary contractions post-stroke. Methods: Elbow-flexor voluntary activation was assessed bilaterally for 10 stroke patients (mean 61.2 ± 12.3 years) and 6 age-matched controls (61.3 ± 14.0 years) by stimulating either the peripheral nerve or the motor cortex during maximal voluntary contractions. Any additional evoked force during maximal contractions implies neural drive is incomplete. Peripheral stimulation can detect deficits at or above the stimulation level, while cortical stimulation can identify suboptimal supraspinal output. Results: Impairments were apparent on the less-affected side in addition to the more-affected side after stroke in voluntary activation, torque, and electromyographic activity (EMG) response. Maximal torque was reduced by 44% on the more-affected and 31% on the less-affected side compared to healthy controls (p < 0.001). Peripheral voluntary activation was reduced to 81% on the more-affected side and 86% on the less-affected side, with healthy subjects at 96% (p < 0.05). Although EMG was bilaterally impaired after stroke, the pattern of response was different between sides. Voluntary activation could not be calculated for cortical stimulation post-stroke due to variability in the evoked force, but EMG results from cortical stimulation showed significant differences in the neural drive to each side. Conclusion: Voluntary activation is impaired bilaterally in the upper-limb after stroke, with reduced cortical connectivity on the more-affected side. Significance: Although the muscle itself did not change post-stroke, altered descending drive and connectivity were the critical factors explaining post-stroke paresis.

Mapping the motor point in the human tibialis anterior muscle

OBJECTIVE Percutaneous electrical stimulation of the motor point permits selective activation of a muscle. However, the definition and number of motor points reported for a given muscle varies. Our goal was to address these problems. METHODS The area, location and number of motor points in human tibialis anterior were examined, using isometric dorsiflexion torque responses to electrical stimuli. Three methods were used: lowest electrical threshold, maximum muscle response, and approximate motor point. RESULTS A single motor point was identified in 39/40 subjects regardless of method. The area of the site of lowest electrical threshold was smaller (median, 35 mm(2)) than those using the maximum muscle response (144 mm(2)) and approximate motor point (132 mm(2)). There was substantial, but not significant, between-subject variation in motor point location. Fifty three percent of motor points would have been missed if located only by reference to anatomical landmarks. CONCLUSIONS These results suggested that the motor points location cannot be determined a priori and that the identification method will affect both area and location. SIGNIFICANCE If it is important to maximally activate a single muscle in isolation, the motor point is best represented by the site producing a maximal but isolated muscle response at the lowest stimulation intensity.

Two-year survival following discharge from hospital after spinal cord injury in Bangladesh

Study design:Mixed retrospective-prospective cohort study.Objectives:To determine 2-year survival following discharge from hospital after spinal cord injury in Bangladesh.Setting:Bangladesh.Methods:Medical records were used to identify all patients admitted in 2011 with a recent spinal cord injury to the Centre for Rehabilitation of the Paralysed, a large Bangladeshi hospital that specialises in care of people with spinal cord injury. Patients or their families were subsequently visited or contacted by telephone in 2014. Vital status and, where relevant, date and cause of death were determined by verbal autopsy.Results:350 of 371 people admitted with a recent spinal cord injury in 2011 were discharged alive from hospital. All but eleven were accounted for two years after discharge (97% follow-up). Two-year survival was 87% (95% CI 83% to 90%). Two-year survival of those who were wheelchair-dependent was 81% (95% CI 76% to 86%). The most common cause of death was sepsis due to pressure ulcers.Conclusion:In Bangladesh, approximately one in five people with spinal cord injury who are wheelchair-dependent die within two years of discharge from hospital. Most deaths are due to sepsis from potentially preventable pressure ulcers.

How much equipment is prescribed for people with spinal cord injury in Australia, do they use it and are they satisfied 1 year later?

Background and purpose:The purpose of this study was to determine the amount and type of equipment prescribed to aid mobility and self-care for patients with spinal cord injuries (SCI) in Australia and to determine how frequently the equipment is used 1 year later and whether patients are satisfied with it.Methods:A consecutive series of 61 patients admitted for rehabilitation to two Sydney SCI units were recruited. All mobility and self-care equipment worth more than

The contribution of twins to the study of cognitive ageing and dementia: The Older Australian Twins Study

AU50 prescribed by therapists before patients’ discharge was recorded. This included wheelchairs, commodes, shower chairs, hoists, electric beds, pressure-relieving cushions, bed mattresses, slideboards, walking aids, orthoses, electrical stimulation systems and other pieces of notable exercise equipment. Patients were interviewed 1 year later and asked about each piece of equipment they had been prescribed. Specifically, they were asked about how frequently they had used each piece of equipment and whether they were satisfied with it. Data were analysed using descriptive statistics.Results:Three hundred and fourteen pieces of equipment, including 68 wheelchairs, were prescribed for the 61 patients. Most of the equipment (226/314) was used more than 20 times in the 2 months preceding the 1-year review. Most patients were satisfied or highly satisfied with the majority of equipment prescribed, although patients were very dissatisfied or only partly dissatisfied with 18/314 pieces of equipment.Discussion:Patients were generally satisfied with the equipment they were prescribed. There was a small amount of equipment prescribed that was not used 1 year later or with which patients were dissatisfied.