Alpha 1 antitrypsin distribution in an allergic asthmatic population sensitized to house dust mites

Background and objective

Severe alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma.

Methods

A cross-sectional cohort study of 648 patients with HDM allergic asthma was carried out. Demographic, clinical and analytical variables were collected. PI*S and PI*Z AAT deficient alleles of the SERPINA1 gene were assayed by real-time PCR.

Results

Asthma was intermittent in 253 patients and persistent in 395 patients (246 mild, 101 moderate and 48 severe). One hundred and forty-five asthmatic patients (22.4%) with at least one mutated allele (S or Z) were identified. No association between the different genotypes and asthma severity was found. No significant differences in all clinical and functional tests, as well as nasal eosinophils, IgA and IgE serum levels were observed. Peripheral eosinophils were significantly lower in patients with the PI*MS genotype (p?=?0.0228). Neither association between deficient AAT genotypes or serum ATT deficiency (AATD) and development of severe asthma, or correlation between ATT levels and FEV1 was observed.

Conclusion

In conclusion, the distribution of AAT genotypes in HDM allergic asthmatic patients did not differ from those found in Spanish population. Neither severe ATTD or deficient AAT genotypes appear to confer different clinical expression of asthma.

     

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.     

A qualitative study exploring parents’ experiences with epinephrine use for their child’s anaphylactic reaction

Background

Children with life threatening food allergies live with the constant threat of a fatal reaction, and caregivers must always be prepared to treat with an epinephrine auto-injector (EAI). This interpretive phenomenological study explored parents’ perceptions and lived experiences with prescribed EAI use for their child.

Methods

The purposive sample included ten parents of five children under 12 years of age, diagnosed with a food allergy and prescribed with an EAI who recently experienced anaphylaxis. Data sources included digitally-recorded semi-structured interviews and a reflexive journal.

Results

Eight main themes emerged: perception of anaphylaxis, life challenges, isolation, anxiety, hesitation, guilt, influence of health care professionals, and lessons learned. Parents uniformly described multiple life challenges and feelings of isolation, anxiety and hesitation during a reaction that lead to subsequent guilt.

Conclusions

Handling reactions correctly provided parents with confidence to treat subsequent reactions. Witnessing the effects of an EAI and receiving positive feedback from health care providers further strengthened their confidence to quickly and competently intervene in future reactions.

     

Regenerative peripheral nerve interfaces for real-time,proportional control of a Neuroprosthetic hand

Introduction

Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control.

Methods

Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs.

Results

Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R²?=?0.758 and R²?=?0.802, respectively).

Conclusion

EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

     

Stochastic resonance stimulation improves balance in children with cerebral palsy: a case control study

Background

Stochastic Resonance (SR) Stimulation has been used to enhance balance in populations with sensory deficits by improving the detection and transmission of afferent information. Despite the potential promise of SR in improving postural control, its use in individuals with cerebral palsy (CP) is novel. The objective of this study was to investigate the immediate effects of electrical SR stimulation when applied in the ankle muscles and ligaments on postural stability in children with CP and their typically developing (TD) peers.

Methods

Ten children with spastic diplegia (GMFCS level I- III) and ten age-matched TD children participated in this study. For each participant the SR sensory threshold was determined. Then, five different SR intensity levels (no stimulation, 25, 50, 75, and 90% of sensory threshold) were used to identify the optimal SR intensity for each subject. The optimal SR and no stimulation condition were tested while children stood on top of 2 force plates with their eyes open and closed. To assess balance, the center of pressure velocity (COPV) in anteroposterior (A/P) and medial-lateral (M/L) direction, 95% COP confidence ellipse area (COPA), and A/P and M/L root mean square (RMS) measures were computed and compared.

Results

For the CP group, SR significantly decreased COPV in A/P direction, and COPA measures compared to the no stimulation condition for the eyes open condition. In the eyes closed condition, SR significantly decreased COPV only in M/L direction. Children with CP demonstrated greater reduction in all the COP measures but the RMS in M/L direction during the eyes open condition compared to their TD peers. The only significant difference between groups in the eyes closed condition was in the COPV in M/L direction.

Conclusions

SR electrical stimulation may be an effective stimulation approach for decreasing postural sway and has the potential to be used as a therapeutic tool to improve balance. Applying subject-specific SR stimulation intensities is recommended to maximize balance improvements. Overall, balance rehabilitation interventions in CP might be more effective if sensory facilitation methods, like SR, are utilized by the clinicians.

Trial registration

ClinicalTrials.gov identifier NCT02456376; 28 May 2015 (Retrospectively registered); https://clinicaltrials.gov/ct2/show/NCT02456376.

     

Control within a virtual environment is correlated to functional outcomes when using a physical prosthesis

Background

Advances such as targeted muscle reinnervation and pattern recognition control may provide improved control of upper limb myoelectric prostheses, but evaluating user function remains challenging. Virtual environments are cost-effective and immersive tools that are increasingly used to provide practice and evaluate prosthesis control, but the relationship between virtual and physical outcomes—i.e., whether practice in a virtual environment translates to improved physical performance—is not understood.

Methods

Nine people with transhumeral amputations who previously had targeted muscle reinnervation surgery were fitted with a myoelectric prosthesis comprising a commercially available elbow, wrist, terminal device, and pattern recognition control system. Virtual and physical outcome measures were obtained before and after a 6-week home trial of the prosthesis.

Results

After the home trial, subjects showed statistically significant improvements (p <?0.05) in offline classification error, the virtual Target Achievement Control test, and the physical Southampton Hand Assessment Procedure and Box and Blocks Test. A trend toward improvement was also observed in the physical Clothespin Relocation task and Jebsen-Taylor test; however, these changes were not statistically significant. The median completion time in the virtual test correlated strongly and significantly with the Southampton Hand Assessment Procedure (p =?0.05, R =???0.86), Box and Blocks Test (p =?0.007, R =???0.82), Jebsen-Taylor Test (p =?0.003, R =?0.87), and the Assessment of Capacity for Myoelectric Control (p =?0.005,R =???0.85). The classification error performance only had a significant correlation with the Clothespin Relocation Test (p =?0.018, R =?.76).

Conclusions

In-home practice with a pattern recognition-controlled prosthesis improves functional control, as measured by both virtual and physical outcome measures. However, virtual measures need to be validated and standardized to ensure reliability in a clinical or research setting.

Trial registration

This is a registered clinical trial: NCT03097978.

     

Effect of high-frequency alternating current transcutaneous stimulation over muscle strength: a controlled pilot study

Background

High-frequency alternating currents of greater than 1 kHz applied on peripheral nerves has been used in animal studies to produce a motor nerve block. It has been evidenced that frequencies higher than 5 kHz are necessary to produce a complete peripheral nerve block in primates, whose nerve thickness is more similar to humans. The aim of the study was to determine the effect on muscle strength after the application of a high-frequency stimulation at 5 and 10 kHz compared to sham stimulation in healthy volunteers.

Findings

Transcutaneous stimulation at 5 kHz, 10 kHz and sham stimulation were applied to eleven healthy volunteers over the ulnar and median nerves for 20 min. Maximal handgrip strength was measured before, during, immediately after the intervention, and 10 min after the end of intervention. The 10 kHz stimulation showed a lower handgrip strength during the intervention (28.1 N, SEM 3.9) when compared to 5 kHz (31.1 N, SEM 3.6; p?<?0.001) and to sham stimulation (33.7 N, SEM 3.9; p?<?0.001). Furthermore, only stimulation at 10 kHz decreased handgrip strength when compared to baseline.

Conclusions

These findings suggest high-frequency stimulation has an inhibitory effect over muscle strength. Future studies are required in patients that are characterized by motor hyperactive such as spasticity or tremors.

Clinical trial registration

NCT, NCT03169049. Registered on 30 May 2017

     

The risk of major cardiovascular events for adults with transfemoral amputation

Background

It is well-known that the risk of cardiac disease is increased for those with lower-limb amputations, likely as a result of the etiology of the amputation. Using a longitudinal population-based dataset, we examined the association between transfemoral amputation (TFA) status and the risk of experiencing a major cardiac event for those undergoing either dysvascular or traumatic amputations. The association of receiving a prosthesis with the risk of experiencing a major cardiac event was also examined.

Methods

Study Population: All individuals with TFA (N 162), i.e. knee disarticulation and transfemoral amputation, residing in Olmsted County, MN, between 1987 and 2014. Each was matched (1:10 ratio) with non-TFA adults on age, sex, and duration of residency.Data Analysis: A competing risk Cox proportional hazard model was used to estimate the relative likelihood of an individual with a TFA experiencing a major cardiac event in a given time period as compared to the matched controls. The cohort was divided by amputation etiology: dysvascular vs trauma/cancer. Additional analysis was performed by combining all individuals with a TFA to look at the relationship between prosthesis receipt and major cardiac events.

Results

Individuals with a dysvascular TFA had an approximately four-fold increased risk of a cardiac event after undergoing an amputation (HR 3.78, 95%CI: 3.07–4.49). These individuals also had an increased risk for non-cardiac mortality (HR 6.27, 95%CI: 6.11–6.58). The risk of a cardiac event was no higher for those with a trauma/cancer TFA relative to the able-bodied controls (HR 1.30, 95%CI: 0.30–5.85). Finally, there was no difference in risk of experiencing a cardiac event for those with or without prosthesis (HR 1.20, 95%CI: 0.55–2.62).

Conclusion

The high risk of initial mortality stemming from an amputation event may preclude many amputees from cardiovascular disease progression. Amputation etiology is also an important factor: cardiac events appear to be more likely among patients with a dysvascular TFA. Providing a prosthesis does not appear to be associated with a reduced risk of a major cardiac event following amputation.

     

The role of exercise testing in predicting successful ambulation with a lower extremity prosthesis: a systematic literature review and clinical practice guideline

Background

Growing discontent with the k-level system for functional classification of patients with limb loss and movement of healthcare toward evidence-based practice has resulted in the need for alternative forms of functional classification and development of clinical practice guidelines to improve access to quality prosthetic interventions. The purpose of this project was to develop and present a clinical practice recommendation for exercise testing in prosthetic patient care based on the results and synthesis of a systematic literature review.

Methods

Database searches of PubMed, Google Scholar, Web of Science, and Cochrane were conducted and articles reviewed. Of the potential 1386 articles 10 met the criteria for inclusion. These articles were assessed using the critical appraisal tool of the United Kingdom National Service Framework for Long-Term Conditions. Of the 10 included articles eight were of high, one of medium, and one of low, quality. Data from these articles were synthesized into 6 empirical evidence statements, all qualifying for research grade A. These statements were used to develop the proposed clinical practice guideline.

Results

While the results of this systematic review were not able to support the direct connection between cardiorespiratory performance and K-levels, the literature did support the ability of exercise testing results to predict successful prosthetic ambulation in some demographics. Both continuous maximum-intensity single lower extremity ergometer propelled by a sound limb and intermittent submaximal upper extremity ergometer protocols were found to be viable evaluation tools of cardiorespiratory fitness and function in the target population.

Conclusion

The ability to sustain an exercise intensity of ≥50% of a predicted VO_2max value in single leg cycle ergometry testing and achievement of a sustained workload of 30 W in upper extremity ergometry testing were found to be the strongest correlates to successful ambulation with a prosthesis. VO₂ values were found to increase in amputee subjects following a 6-week exercise program. These synthesized results of the systematic literature review regarding exercise testing in patients with loss of a lower extremity were used to develop and a present a clinical treatment pathway.

     

A hybrid image fusion system for endovascular interventions of peripheral artery disease

Purpose

Interventional endovascular treatment has become the first line of management in the treatment of peripheral artery disease (PAD). However, contrast and radiation exposure continue to limit the feasibility of these procedures. This paper presents a novel hybrid image fusion system for endovascular intervention of PAD. We present two different roadmapping methods from intra- and pre-interventional imaging that can be used either simultaneously or independently, constituting the navigation system.

Methods

The navigation system is decomposed into several steps that can be entirely integrated within the procedure workflow without modifying it to benefit from the roadmapping. First, a 2D panorama of the entire peripheral artery system is automatically created based on a sequence of stepping fluoroscopic images acquired during the intra-interventional diagnosis phase. During the interventional phase, the live image can be synchronized on the panorama to form the basis of the image fusion system. Two types of augmented information are then integrated. First, an angiography panorama is proposed to avoid contrast media re-injection. Information exploiting the pre-interventional computed tomography angiography (CTA) is also brought to the surgeon by means of semiautomatic 3D/2D registration on the 2D panorama. Each step of the workflow was independently validated.

Results

Experiments for both the 2D panorama creation and the synchronization processes showed very accurate results (errors of 1.24 and \(2.6 \pm 1.4\) mm, respectively), similarly to the registration on the 3D CTA (errors of \(1.5 \pm 0.7\) mm), with minimal user interaction and very low computation time. First results of an on-going clinical study highlighted its major clinical added value on intraoperative parameters.

Conclusion

No image fusion system has been proposed yet for endovascular procedures of PAD in lower extremities. More globally, such a navigation system, combining image fusion from different 2D and 3D image sources, is novel in the field of endovascular procedures.