Smart dry powder inhalers and intelligent adherence management.

Adherence to inhaled treatments is a complex challenge for patients with chronic obstructive pulmonary disease (COPD) and asthma, it not only involves following the prescribed treatment plans but also administering the medications correctly. When using a dry powder inhaler (DPI), the inhalation flow is particularly critical. Patients frequently fail to use a rapid enough onset and fast enough inhalation when using DPIs. At the same time, there is increasing pressure on physicians to switch patients to DPIs, to minimise the environmental impact of pMDI propellants. This makes it critical to understand whether a patient will maintain or improve disease control by using their new inhaler correctly. However, it is challenging for health care professionals to understand how a patient behaves away from the clinic. Therefore, it would be beneficial to obtain real-world data through the use of monitoring tools, i.e., "smart inhalers". This paper reviews the technologies used to monitor DPIs, how effective they have been in a clinical setting, and how well these have been adopted by patients and health care providers.

Peripheral Electrical Stimulation Modulates Cortical Beta-Band Activity.

Low-frequency peripheral electrical stimulation using a matrix electrode (PEMS) modulates spinal nociceptive pathways. However, the effects of this intervention on cortical oscillatory activity have not been assessed yet. The aim of this study was to investigate the effects of low-frequency PEMS (4 Hz) on cortical oscillatory activity in different brain states in healthy pain-free participants. In experiment 1, PEMS was compared to sham stimulation. In experiment 2, motor imagery (MI) was used to modulate the sensorimotor brain state. PEMS was applied either during MI-induced oscillatory desynchronization (concurrent PEMS) or after MI (delayed PEMS) in a cross-over design. For both experiments, PEMS was applied on the left forearm and resting-state electroencephalography (EEG) was recording before and after each stimulation condition. Experiment 1 showed a significant decrease of global resting-state beta power after PEMS compared to sham (p = 0.016), with a median change from baseline of -16% for PEMS and -0.54% for sham. A cluster-based permutation test showed a significant difference in resting-state beta power comparing pre- and post-PEMS (p = 0.018) that was most pronounced over bilateral central and left frontal sensors. Experiment 2 did not identify a significant difference in the change from baseline of global EEG power for concurrent PEMS compared to delayed PEMS. Two cluster-based permutation tests suggested that frontal beta power may be increased following both concurrent and delayed PEMS. This study provides novel evidence for supraspinal effects of low-frequency PEMS and an initial indication that the presence of a cognitive task such as MI may influence the effects of PEMS on beta activity. Chronic pain has been associated with changes in beta activity, in particular an increase of beta power in frontal regions. Thus, brain state-dependent PEMS may offer a novel approach to the treatment of chronic pain. However, further studies are warranted to investigate optimal stimulation conditions to achieve a reduction of pain.

Alpha entrainment drives pain relief using visual stimulation in a sample of chronic pain patients: a proof-of-concept controlled study.

One-third of the population in the UK and worldwide struggle with chronic pain. Entraining brain alpha activity through noninvasive visual stimulation has been shown to reduce experimental pain in healthy volunteers. Neural oscillations entrainment offers a potential noninvasive and nonpharmacological intervention for patients with chronic pain, which can be delivered in the home setting and has the potential to reduce use of medications. However, evidence supporting its use in patients with chronic pain is lacking. This study explores whether (a) alpha entrainment increase alpha power in patients and (b) whether this increase in alpha correlates with analgesia. In total, 28 patients with chronic pain sat in a comfortable position and underwent 4-min visual stimulation using customised goggles at 10 Hz (alpha) and 7 Hz (control) frequency blocks in a randomised cross-over design. 64-channel electroencephalography and 11-point numeric rating scale pain intensity and pain unpleasantness scores were recorded before and after stimulation. Electroencephalography analysis revealed frontal alpha power was significantly higher when stimulating at 10 Hz when compared to 7 Hz. There was a significant positive correlation between increased frontal alpha and reduction in pain intensity (r = 0.33; P < 0.05) and pain unpleasantness (r = 0.40; P < 0.05) in the 10 Hz block. This study provides the first proof of concept that changes in alpha power resulting from entrainment correlate with an analgesic response in patients with chronic pain. Further studies are warranted to investigate dose-response parameters and equivalence to analgesia provided by medications.

Entraining Alpha Activity Using Visual Stimulation in Patients With Chronic Musculoskeletal Pain: A Feasibility Study.

Entraining alpha activity with rhythmic visual, auditory, and electrical stimulation can reduce experimentally induced pain. However, evidence for alpha entrainment and pain reduction in patients with chronic pain is limited. This feasibility study investigated whether visual alpha stimulation can increase alpha power in patients with chronic musculoskeletal pain and, secondarily, if chronic pain was reduced following stimulation. In a within-subject design, 20 patients underwent 4-min periods of stimulation at 10 Hz (alpha), 7 Hz (high-theta, control), and 1 Hz (control) in a pseudo-randomized order. Patients underwent stimulation both sitting and standing and verbally rated their pain before and after each stimulation block on a 0-10 numerical rating scale. Global alpha power was significantly higher during 10 Hz compared to 1 Hz stimulation when patients were standing (t = -6.08, p < 0.001). On a more regional level, a significant increase of alpha power was found for 10 Hz stimulation in the right-middle and left-posterior region when patients were sitting. With respect to our secondary aim, no significant reduction of pain intensity and unpleasantness was found. However, only the alpha stimulation resulted in a minimal clinically important difference in at least 50% of participants for pain intensity (50%) and unpleasantness ratings (65%) in the sitting condition. This study provides initial evidence for the potential of visual stimulation as a means to enhance alpha activity in patients with chronic musculoskeletal pain. The brief period of stimulation was insufficient to reduce chronic pain significantly. This study is the first to provide evidence that a brief period of visual stimulation at alpha frequency can significantly increase alpha power in patients with chronic musculoskeletal pain. A further larger study is warranted to investigate optimal dose and individual stimulation parameters to achieve pain relief in these patients.

Acceptability and usability of smartphone-based brainwave entrainment technology used by individuals with chronic pain in a home setting.

BACKGROUND: Brainwave entrainment (BWE) using rhythmic visual or auditory stimulation has many potential clinical applications, including the management of chronic pain, where there is a pressing need for novel, safe and effective treatments. The aim of this study was to gain qualitative feedback on the acceptability and usability of a novel BWE smartphone application, to ensure it meets the needs and wishes of end users. METHODS: Fifteen participants with chronic pain used the application at home for 4 weeks. Semi-structured telephone interviews were then carried out. A template analysis approach was used to interpret the findings, with an initial coding template structured around the constructs of a theoretical framework for assessing acceptability of healthcare interventions. Structured data analysis generated a final modified coding structure, capturing themes generated across participants' accounts. RESULTS: The four main themes were 'approach to trying out the app: affective attitude and ethicality', 'perceived effectiveness', 'opportunity costs and burden' and 'intervention coherence and self-efficacy'. All participants were willing to engage with the technology and welcomed it as an alternative approach to medications. Participants appreciated the simplicity of design and the ability to choose between visual or auditory stimulation. All the participants felt confident in using the application. CONCLUSION: The findings demonstrate preliminary support for the acceptability and usability of the BWE application. This is the first qualitative study of BWE to systematically assess these issues.

Is Transcranial Direct Current Stimulation (tDCS) Effective for the Treatment of Pain in Fibromyalgia? A Systematic Review and Meta-Analysis.

BACKGROUND: Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment. OBJECTIVE: To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia. METHODS: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals. RESULTS: Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made. CONCLUSIONS: tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies. PERSPECTIVE: This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.

Transcranial Alternating Current Stimulation at Alpha Frequency Reduces Pain When the Intensity of Pain is Uncertain.

Alpha activity directly before pain onset has been implicated in pain experience with higher prestimulus alpha associated with lower reported pain. However, expectations about pain intensity also seem to affect prestimulus alpha activity. To date, evidence for a relationship between alpha activity and pain experience has been largely correlational. Transcranial alternating current stimulation at alpha frequency (alpha tACS) permits direct manipulation of alpha activity and therefore an examination of the potential causal relationship between alpha activity and pain. We investigated whether somatosensory alpha tACS could reduce pain experience and whether this was influenced by uncertainty about pain intensity. In a within-subjects design, perceived pain intensity and unpleasantness were assessed in 23 participants during alpha tACS and sham stimulation. Visual cues preceding the pain stimulus were used to manipulate uncertainty. A significant tACS × Uncertainty × Stimulus intensity interaction was found for reported pain intensity (F2,44 = 4.50, P = .017, partial η2 = .17) and unpleasantness (F1,22 = 4.78, P = .040, partial η2 = .18). Pain experience during the application of somatosensory alpha tACS was significantly lowered compared with sham stimulation, but only when the intensity of an upcoming stimulus was uncertain. PERSPECTIVE: To our knowledge, this is the first study to suggest that somatosensory alpha tACS might lead to a reduction in pain. Interventions targeting alpha activity may have the potential to alleviate chronic pain. However, a patient's expectation about the intensity of upcoming pain must also be taken into account.

Altered cortical responsiveness to pain stimuli after high frequency electrical stimulation of the skin in patients with persistent pain after inguinal hernia repair.

BACKGROUND: High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. MATERIALS AND METHODS: Nineteen male patients; 9 with and 10 without persistent pain after inguinal hernia repair received HFS. Before, directly after and thirty minutes after HFS evoked potentials and the subjective pain intensity were measured in response to electric pain stimuli applied to the surrounding unconditioned skin. RESULTS: The results show that, thirty minutes after HFS, the ERP N1 amplitude observed at the conditioned arm was statistically significantly larger than the amplitude at the control arm across all patients. No statistically significant differences were observed regarding ERP N1 amplitude between patients with and without persistent pain. However, thirty minutes after HFS we did observe statistically significant differences of P2 amplitude at the conditioned arm between the two groups. The P2 amplitude decreased in comparison to baseline in the group of patients with pain. CONCLUSION: The ERP N1 effect, induced after HFS, was not different between patients with vs. without persistent pain. The decreasing P2 amplitude was not observed in the patients without pain and also not in the previous healthy volunteer study and thus might be a marker for altered cortical sensory processing in patients with persistent pain after surgery.