Physical activity and health outcomes in persons with haemophilia B

Regular participation in physical activity helps to prevent damage and maintain joint health in persons with haemophilia. This study describes self‐reported physical activity participation among a sample of people with haemophilia B in the US and measures its association with health‐related quality of life (HRQoL). Data on 135 participants aged 5–64 years were abstracted from Hemophilia Utilization Group Study Part Vb. The International Physical Activity Questionnaire assessed physical activity among participants aged 15–64 years, and the Children's Physical Activity Questionnaire abstracted from the Canadian Community Health Survey was used for participants aged 5–14 years. SF‐12 was used to measure HRQoL and the EuroQol (EQ‐5D‐3L) was used to measure health status for participants older than 18 years of age. PedsQL was used to measure HRQoL in children aged 5–18 years. Sixty‐two percent of participants in the 15–64 year‐old age cohort reported a high level of physical activity, 29% reported moderate activity and 9% reported low activity. For children aged 5–14 years, 79% reported participating in physical activity for at least 4 days over a typical week. Based on the 2008 Physical Activity Guidelines for Americans, 79% of adults achieved the recommended physical activity level. Multivariable regression models indicated that adults who engaged in a high level of physical activity reported EQ‐5D Visual Analogue Scale (VAS) scores that were 11.7 (P = 0.0726) points greater than those who engaged in moderate/low activity, indicating better health outcomes. Among children, no statistically significant differences in health outcomes were found between high and moderate or low activity groups.     

Validation of the Chinese version of the Canadian Haemophilia Outcomes‐Kids' Life Assessment Tool (the CHO‐KLAT)

It is important to assess the health‐related quality of life outcomes of boys in China, but there are no tools validated for this purpose. The objective of the study was to assess the validity of the Simplified Chinese version of the CHO‐KLAT_2.0. We recruited 60 boys with either haemophilia A (HA) or haemophilia B (HB) and their parents from four regions in China, and assessed the validity of CHO‐KLAT compared to the PedsQL. All participants complete the CHO‐KLAT a second time 1–2 weeks later to assess reliability. The boys ranged in age from 7 to 18 (mean = 12.4; SD = 3.03) years. The severity distribution was: mild (9), moderate (10) and severe (41). On‐demand therapy was received by 26 boys, while 18 received low‐dose prophylaxis (HA: 10 IU kg^?1 2–3 times week^?1, and HB: 20 IU kg^?1 1 time week^?1). The mean CHO‐KLAT scores were 63.7 (SD = 10.6) for child‐report and 58.3 (SD = 11.4) for parent‐report. Validity was supported by a correlation of 0.67 (P < 0.0001) with the PedsQL for child‐report and 0.64 (P < 0.0001) for parent‐report. The test–retest reliability was 0.88 (95% CI: 0.82–0.94) for child‐report, and 0.90 (95% CI: 0.86–0.95) for parent‐report. Inter‐rater reliability was 0.46 (95% CI: 0.26–0.66). CHO‐KLAT scores were 11 points higher among patients who had been on prophylaxis 3 times per week for ≥24 weeks. These results confirm the reliability and validity of the Chinese version of the CHO‐KLAT. This measure is suitable for use in prospective clinical trials in boys with haemophilia in China.     

‘Train‐the‐Trainer’: an effective and successful model to accelerate training and improve physiotherapy services for persons with haemophilia in China

The objective of this study was to teach a small group of Chinese physiatrists and physiotherapists to: (i) become trainers and leaders in haemophilia physiotherapy (PT) care in China and (ii) to acquire rapid proficiency in using the reliable and validated Hemophilia Joint Health Score (HJHS) for evaluating musculoskeletal health in boys with haemophilia. Two experienced Canadian physiotherapists and co‐developers of the HJHS moderated a 4‐day PT training workshop with six Chinese participants. Emphasis was placed on instruction and practice in administering the HJHS. Practical sessions with haemophilia patients were interchanged with theory (power point presentations) and interactive question and answer periods. A proficient, knowledgeable translator was an essential component of the workshop. Upon workshop completion, the six trainees demonstrated improved haemophilia‐specific PT knowledge and were fully familiar with the HJHS and its administration. The latter was assessed in a mini‐reliability study. The ‘Train‐the‐Trainer’ model is a very effective education programme designed to accelerate training in haemophilia PT to meet the rapidly increasing need for haemophilia‐specific rehabilitation services in a very large country such as China. It is anticipated that physiatrists/physiotherapists at newly established Chinese haemophilia treatment centres will receive training in haemophilia care as a result of this unique programme in the immediate future.     

From the Cover: Wireless power transfer to deep-tissue microimplants

The ability to implant electronic systems in the human body has led to many medical advances. Progress in semiconductor technology paved the way for devices at the scale of a millimeter or less (“microimplants”), but the miniaturization of the power source remains challenging. Although wireless powering has been demonstrated, energy transfer beyond superficial depths in tissue has so far been limited by large coils (at least a centimeter in diameter) unsuitable for a microimplant. Here, we show that this limitation can be overcome by a method, termed midfield powering, to create a high-energy density region deep in tissue inside of which the power-harvesting structure can be made extremely small. Unlike conventional near-field (inductively coupled) coils, for which coupling is limited by exponential field decay, a patterned metal plate is used to induce spatially confined and adaptive energy transport through propagating modes in tissue. We use this method to power a microimplant (2 mm, 70 mg) capable of closed-chest wireless control of the heart that is orders of magnitude smaller than conventional pacemakers. With exposure levels below human safety thresholds, milliwatt levels of power can be transferred to a deep-tissue (>5 cm) microimplant for both complex electronic function and physiological stimulation. The approach developed here should enable new generations of implantable systems that can be integrated into the body at minimal cost and risk.Progress in semiconductor technology has led to electronic devices that can augment or replace physiological functions; their ability to be implanted for direct interaction with organ systems relies on overall miniaturization of the device for simplified delivery (e.g., via catheter or hypodermic needle) and access to interstitial spaces. Advances over the past few decades enable most components in a biomedical device, including electrodes, oscillators, memory, and wireless communication systems, to be integrated on tiny silicon chips. However, the energy required for electronic function remains substantial and the consumption density has not been matched by existing powering technologies (1). As a result, the vast bulk of most implantable electronic devices consists of energy storage or harvesting components.Although considerable progress has been made in energy storage technologies, batteries remain a major obstacle to miniaturization (2, 3) because their lifetimes are limited and highly constrained by the available volume, requiring periodic surgical replacement once the unit is depleted. Energy-harvesting strategies have been developed to eliminate batteries or to extend their function. Previous demonstrations include thermoelectric (4), piezoelectric (5–7), biopotential (8), or glucose (9, 10) power extraction. However, these methods are anatomically specific and, in their existing forms, yield power densities too low (<0.1 μW/mm²) for a microimplant.Alternatively, energy can be transferred from an external source. Ideally, power transfer should be completely noninvasive and not specific to regions in the body. Most existing approaches for this type of transfer are based on electromagnetic coupling in the near field (11–20). Though well-suited for large devices and prostheses (21, 22), near-field methods do not address key challenges to powering a microimplant: weak coupling between extremely asymmetric source and receiver structures (23), dissipative and heterogeneous tissue (24), and regulatory power thresholds for general safety (25). These challenges, compounded by the intrinsic exponential decay of the near field, severely limit miniaturization beyond superficial depths (>1 cm), even if the battery can be removed.Theory has indicated that these problems can be overcome in the electromagnetic midfield (23): energy transfer in this region, defined to be about a wavelength’s distance from the source, occurs through the coupling between evanescent fields in air and propagating modes in tissue. Using a patterned metal plate to control the near field, we demonstrate milliwatt levels of power transfer to a miniaturized coil deep in heterogeneous tissue (>5 cm), with exposure levels below safety thresholds for humans; this enables us to power a microimplant capable of delivering controlled electrical pulses to nearly anywhere in the body. The device consists of a multiturn coil structure, rectifying circuits for AC/DC power conversion, a silicon-on-insulator integrated circuit (IC) for pulse control, and electrodes, entirely assembled within a 2-mm diameter, 3.5-mm height device small enough to fit inside a catheter. We demonstrate wireless function by operating it in human-scale heart and brain environments, and by wirelessly regulating cardiac rhythm through a chest wall.     

Altered immune function associated with disordered neural connectivity and executive dysfunctions: A neurophysiological study on children with autism spectrum disorders

Previous studies have shown that children with autism spectrum disorders (ASDs) have impaired executive function, disordered neural connectivity, and abnormal immunologic function. The present study examined whether these abnormalities were associated. Seventeen high-functioning (HFA) and 17 low-functioning (LFA) children with ASD, aged 8–17 years, participated voluntarily in the study. The two groups of children were compared on their general intelligence in terms of IQ; executive function as measured by the Hong Kong List Learning Test, D2 Test of Concentration, Five Point Test, Children's Color Trail Test, Tower of California Test, and Go/No-Go task; a non-executive task as measured by the Picture Completion Task; neural connectivity as measured by theta coherence in the anterior and posterior regions; and immunologic function as measured by the level of circulating CD3+ CD8+ suppressor/cytotoxic T lymphocytes in a blood sample. Results on executive function showed that LFA children performed significantly poorer than HFA children as shown on their lower Executive Composite as well as individual executive function scores. However, there was no group difference on the Picture Completion Task. Results on neural connectivity showed that LFA children demonstrated a different pattern of electroencephalography (EEG) coherence from HFA children as shown in the significantly elevated theta coherence in the anterior network, as well as at the left intra-hemispheric (LA-LP) and right-to-left inter-hemisphere (RA-LP) connections of LFA children. In immunologic function, results showed that LFA children had significantly elevated level of suppressor/cytotoxic T lymphocytes (CD3+ CD8+) (p < 0.05). In addition, the executive dysfunction, disordered neural connectivity, and abnormal immunologic function were found to be associated. These results provided some initial evidence to support the notion that immunologic factors are associated with neuronal damage, measureable by EEG coherence and manifested as executive dysfunctions.