A quantitative evaluation of adherence and inhalation technique among respiratory patients: An observational study using an electronic inhaler assessment device.

BACKGROUND: Problems related to poor adherence and inhaler technique (IT) are historically reported in the literature. Most common methods used for adherence and IT assessment are reported to be either inaccurate or subjective. Few electronic monitoring devices (EMDs) that provide an objective measure of both adherence and IT while patients use inhalers at home now exist. Therefore, this study aimed to examine adherence level and IT among respiratory patients in community care using such an EMD for the first time in England. METHODS: A prospective, multicentre, observational cohort study was conducted. Patients with chronic obstructive pulmonary disease (COPD) or asthma were recruited from independent community pharmacies within West and South London. Patients were provided with a dry-powder inhaler (DPI) mounted with an EMD to use for 1 month. Adherence was also assessed using pharmacy dispensing data, inhaler dose counter and self-reporting. RESULTS: Data were available for 48 patients. Only eight patients used their inhaler in the correct manner at the correct interval as identified by the chosen EMD. The median actual adherence rate, as measured by the EMD, was 42.7%. This was significantly different from the median dose counter adherence (100%), medication refill adherence (MRA) (100%), proportions of days covered (PDC) (97.8%) and self-reported adherence (P < .001, each). Within a 1-month period, there were 2188 files showing attempted use of the DPI, of which 840 had IT errors. The median technique error rate (TER) was 30.1%. Most common errors recorded were as follows: multiple inhalations, drug priming without inhalation and failure to prime the device correctly. CONCLUSION: The current study demonstrates that measures such as dose counter, prescription refill and self-reporting showed a high level of adherence among the observed patients. However, the objective data provided by the EMD showed a significantly lower actual adherence rate, reflecting how adherence remains variable and problematic among patients in the community.

Inadequate assessment of adherence to maintenance medication leads to loss of power and increased costs in trials of severe asthma therapy: results from a systematic literature review and modelling study.

Adherence to inhaled maintenance therapy in severe asthma is rarely adequately assessed, and its influence on trial outcomes is unknown. We systematically determined how adherence to maintenance therapy is assessed in clinical trials of "add-on" therapy for severe asthma. We model the improvement in trial power that could be achieved by accurately assessing adherence.A systematic search of six major databases identified randomised trials of add-on therapy for severe asthma. The relationship between measuring adherence and study outcomes was assessed. An estimate of potential improvements in statistical power and sample size was derived using digitally recorded adherence trial data.87 randomised controlled trials enrolling 22 173 participants were included. Adherence assessment was not reported in 67 trials (n=13 931, 63%). Studies that reported adherence used a range of self-report and subjective methods. None of the studies employed an objective assessment of adherence. Studies that reported adherence had a significantly reduced pooled variance in forced expiratory volume in 1 s (FEV1) compared to those that did not assess adherence: s2=0.144 L2 versus s2=0.168 L2, p<0.0001. Power to detect clinically relevant changes in FEV1 was significantly higher in trials that reported adherence assessment (mean power achieved 59% versus 49%). Modelling suggests that up to 50% of variance in FEV1 outcomes is attributable to undetected variations in adherence. Controlling for such variations could potentially halve the required sample size.Few trials of add-on therapy monitor adherence to maintenance inhaled therapy, resulting in a greater variance in trial outcomes and inadequate power for determining efficacy.

A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma.

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.

Objective Assessment of Adherence to Inhalers by Patients with Chronic Obstructive Pulmonary Disease.

RATIONALE: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported. OBJECTIVES: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA). METHODS: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use. MEASUREMENTS AND MAIN RESULTS: Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV1 was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure "actual adherence" was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique. CONCLUSIONS: These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.

Response to Bronchodilators Administered via Different Nebulizers in Patients With COPD Exacerbation.

BACKGROUND: The recommended treatment of COPD exacerbations includes administration of short-acting bronchodilators that act to reverse bronchoconstriction, restore lung volumes, and relieve breathlessness. In vitro studies demonstrate vibrating mesh nebulizers (VMNs) provide greater drug delivery to the airway compared to standard small-volume nebulizers (SVNs). We examined whether the physiological and symptom response to nebulized bronchodilators during a COPD exacerbation differed between these 2 modes of bronchodilator delivery. METHODS: Subjects hospitalized with a COPD exacerbation participated in a comparative clinical effectiveness study of 2 methods of nebulization. Using block randomization, 32 participants in this open-label trial were administered salbutamol 2.5 mg/ipratropium bromide 0.5 mg via vibrating mesh (VMN group, n = 16) or small-volume jet nebulizer (SVN group, n = 16) on one occasion. Spirometry, body plethysmography, and impulse oscillometry were performed and Borg breathlessness scores recorded pre bronchodilator and at 1 h post bronchodilator. RESULTS: Baseline demographics were comparable between groups. Mean FEV1 was 48% predicted. Significant changes in lung volumes and airway impedance were seen in both groups. Inspiratory capacity (IC) increased by 0.27 ± 0.20 L and 0.21 ± 0.20 L in the VMN and SVN group, respectively, between group difference P = .40. FVC increased in the VMN group by 0.41 ± 0.40 L compared to 0.19 ± 0.20 L with SVN, between group difference P = .053; and residual volume (RV) decreased by 0.36 ± 0.80 L and 0.16 ± 0.50 L in the VMN and SVN group, respectively, between group difference P = .41. The VMN group had a significant reduction in Borg breathlessness score, P = .034. CONCLUSIONS: Greater improvement in symptoms, and larger absolute change in FVC, was observed in response to equivalent doses of standard bronchodilators administered by VMN, compared to SVN, but no substantial difference in change in IC.

Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial.

BACKGROUND: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods. METHODS: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete. FINDINGS: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 µg daily to 1000 µg daily (500 µg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 µg once daily to 500 µg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA. INTERPRETATION: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden. FUNDING: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline.

The Impact of Biofeedback on Self-Efficacy in Adults with Asthma: A Cross-Sectional Descriptive Survey.

Purpose: Educating patients to self-manage chronic diseases such as asthma is a key role for nurses. The success of this education is often limited by low patient self-efficacy. In this study, we hypothesized that the self-efficacy of patients could be enhanced if their education was based on biofeedback of their own self-management, following a nurse led educational intervention. Patients and Methods: Patients with severe and uncontrolled asthma from one centre who participated in an eight-month, nurse-led asthma education and dose adjustment Randomised Control Trial (RCT) were studied (NCT02307669). Inhaler adherence and technique of use were objectively assessed using a validated digital device. The data recorded on this device was used as the basis for the individualised biofeedback. The Asthma Self-efficacy Questionnaire was used to assess self-efficacy. Results: A total of 88 participants (44 in each group) completed the asthma self-efficacy questionnaire at the end of the study. The mean overall level of self-efficacy was high across both groups; 91 (8.7), with both biofeedback and standard care groups having similarly high levels of self-efficacy, biofeedback group: 89 (10) and standard care group 93 (6). Self-efficacy was not related to objective measures of adherence at either the start of the study, 68 (26), p=0.23, or the end of the study, 58 (32), p=0.62. It was also not related to peak expiratory flow (PEF) at the end of the study in either group (r2= 0.0245, p=0.14). Self-efficacy was related to asthma control test (ACT), 18 (5.5), p=0.0014 and quality-of-life measures; EuroQol (EQ5D3L) 6.4 (1.5) p=0.02. Conclusion: Repeated nurse-delivered education results in high levels of self-efficacy among patients with severe asthma. A high level of perceived self-efficacy should not be assumed to result in higher inhaler adherence.

The Contribution of Oral and Inhaled Glucocorticoids to Adrenal Insufficiency in Asthma.

BACKGROUND: Exposure to any form of glucocorticoid preparation is associated with a risk of adrenal insufficiency (AI). OBJECTIVE: To establish the contribution of oral corticosteroid (OCS) and inhaled corticosteroid (ICS) exposure to the risk of AI in a cohort of patients (n = 80) with severe, uncontrolled asthma. METHODS: We compiled individualized cumulative OCS and ICS exposure data using a combination of health care records and electronic inhaler monitoring using an Inhaler Compliance Assessment device and estimated the risk of AI for each participant using a morning serum cortisol concentration. RESULTS: The predicted prevalence of AI based on morning cortisol concentrations was 25% (20 of 80). Participants on maintenance OCS therapy had the highest risk of AI at 60% (6 of 10) compared with 17% (11 of 65) in those with no recent OCS exposure. Morning serum cortisol correlated negatively with both OCS exposure (mg/kg prednisolone) (r = -0.4; P < .0002) and ICS exposure (mg/kg fluticasone propionate) (r = -0.26; P = .019). Logistic regression of risk of AI against the number of standard treatment courses of OCS demonstrated a positive relationship although this did not reach statistical significance (odds ratio, 1.41; 95% CI, 0.97-2.05; P = .073). Logistic regression analysis, categorizing patients as high-risk AI (cortisol <130 nmol/L) or not (cortisol >130 nmol/L), showed that cumulative ICS exposure remained a significant predictor of AI, even when exposure to OCS was controlled for (odds ratio, 2.17 per 1 mg/kg increase in cumulative fluticasone propionate exposure; 95% CI, 1.06-4.42; P = .033). CONCLUSIONS: Our data suggest that AI is common among patients with asthma and highlights that the risk of AI is associated with both high-dose ICS therapy and intermittent treatment courses of OCS.

A Clinical Perspective on the Role of Electronic Devices in Monitoring and Promoting Adherence in Airways Disease.

Poor adherence to treatment is a common reason why patients with chronic disease have worse outcomes than might be expected. Poor treatment adherence is of particular concern among people with airways disease because, apart from not taking treatment as prescribed, inhaled medication can also be administered incorrectly. Recently, a number of technological advances that accurately document when an inhaled treatment has been used and, in certain instances, how it was used have been developed. There is good evidence from a number of research groups that these devices, either by patient reminders or physician feedback, promote adherence to inhaled treatments. What is less certain is how, in a real-world setting, these devices change outcomes. In this perspective article, the role of electronic devices in quantifying treatment use and addressing poor treatment adherence and their potential role in clinical practice outside of clinical validation trials are described.

The effectiveness of continuous respiratory rate monitoring in predicting hypoxic and pyrexic events: a retrospective cohort study.

Respiratory rate (RR) is routinely used to monitor patients with infectious, cardiac and respiratory diseases and is a component of early warning scores used to predict patient deterioration. However, it is often measured visually with considerable bias and inaccuracy.Objectives. Firstly, to compare distribution and accuracy of electronically measured RR (EMRR) and visually measured RR (VMRR). Secondly, to determine whether, and how far in advance, continuous electronic RR monitoring can predict oncoming hypoxic and pyrexic episodes in infectious respiratory disease.Approach.A retrospective cohort study analysing the difference between EMRR and VMRR was conducted using patient data from a large tertiary hospital. Cox proportional hazards models were used to determine whether continuous, EMRR measurements could predict oncoming hypoxic (SpO2 < 92%) and pyrexic (temperature >38 °C) episodes.Main results.Data were gathered from 34 COVID-19 patients, from which a total of 3445 observations of VMRR (independent of Hawthorne effect), peripheral oxygen saturation and temperature and 729 117 observations of EMRR were collected. VMRR had peaks in distribution at 18 and 20 breaths per minute. 70.9% of patients would have had a change of treatment during their admission based on the UK's National Early Warning System if EMRR was used in place of VMRR. An elevated EMRR was predictive of hypoxic (hazard ratio: 1.8 (1.05-3.07)) and pyrexic (hazard ratio: 9.7 (3.8-25)) episodes over the following 12 h.Significance.Continuous EMRR values are systematically different to VMRR values, and results suggest it is a better indicator of true RR as it has lower kurtosis, higher variance, a lack of peaks at expected values (18 and 20) and it measures a physiological component of breathing directly (abdominal movement). Results suggest EMRR is a strong marker of oncoming hypoxia and is highly predictive of oncoming pyrexic events in the following 12 h. In many diseases, this could provide an early window to escalate care prior to deterioration, potentially preventing morbidity and mortality.

Patient-Selected Treatment Goals in Severe Asthma.

BACKGROUND: Goal-orientated health care accounts for patient preferences and values, not just physician treatment aims. The Global Initiative for Asthma (GINA) management strategy states that clinicians should elicit patients' own treatment goals as a central part of care. Despite this recommendation, data on patients' treatment goals are sparse among patients with severe asthma. OBJECTIVE: The objective of this study is to investigate the relationship between rates of treatment adherence and goal achievement, and patient-selected goals. METHODS: Thematic analysis was used to characterize patient-selected goals. Previously undescribed goal categories in asthma were identified, quantified, and related to clinical characteristics. Goal achievement was aligned with objectively measured treatment adherence. RESULTS: Three categories of patients-selected goals were identified from 2 randomized control trials: disease-specific (n = 98 [51%] and n = 92 [54%], respectively), function-related (n = 90 [48%] and n = 61 [36%]), and knowledge (n = 1 [1%] and n = 17 [10%]). Only 53% of goals aligned with clinician treatment goals. Patients who chose disease-specific goals were more likely to achieve both control and their specified goal (n = 98 [45%], odds ratio: 1.789, confidence interval: 1.066-3.001). Male participants are more likely to focus on disease-specific goals. Patients who achieved their goals were more likely to be T2-high, have an elevated fractional exhaled nitric oxide (FeNO) at their first visit, and have a lower FeNO value at their final visit. Interestingly, adherence rates decline significantly for those who achieve their goals. CONCLUSION: Almost half of patient-selected goals do not align with GINA clinical asthma management goals. Participants who chose goals that do align with clinicians were more likely to achieve them.

Effects of non-invasive respiratory support on gas exchange and outcomes in COVID-19 outside the ICU.

Non-invasive respiratory support (NRS) outside of the ICU has played an important role in the management of COVID-19 pneumonia. There is little data to guide selection of NRS modality. We present outcomes of NRS outside the ICU and discuss the effects of NRS on gas exchange with implications for management.

Current applications of machine learning in the screening and diagnosis of glaucoma: a systematic review and Meta-analysis.

AIM: To compare the effectiveness of two well described machine learning modalities, ocular coherence tomography (OCT) and fundal photography, in terms of diagnostic accuracy in the screening and diagnosis of glaucoma. METHODS: A systematic search of Embase and PubMed databases was undertaken up to 1st of February 2019. Articles were identified alongside their reference lists and relevant studies were aggregated. A Meta-analysis of diagnostic accuracy in terms of area under the receiver operating curve (AUROC) was performed. For the studies which did not report an AUROC, reported sensitivity and specificity values were combined to create a summary ROC curve which was included in the Meta-analysis. RESULTS: A total of 23 studies were deemed suitable for inclusion in the Meta-analysis. This included 10 papers from the OCT cohort and 13 from the fundal photos cohort. Random effects Meta-analysis gave a pooled AUROC of 0.957 (95%CI=0.917 to 0.997) for fundal photos and 0.923 (95%CI=0.889 to 0.957) for the OCT cohort. The slightly higher accuracy of fundal photos methods is likely attributable to the much larger database of images used to train the models (59 788 vs 1743). CONCLUSION: No demonstrable difference is shown between the diagnostic accuracy of the two modalities. The ease of access and lower cost associated with fundal photo acquisition make that the more appealing option in terms of screening on a global scale, however further studies need to be undertaken, owing largely to the poor study quality associated with the fundal photography cohort.

Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial.

BACKGROUND: Guidelines recommend that patients treated with inhalers receive adherence counseling and device training. Digital technologies that assess both inhaler adherence and technique have been developed. Using these technologies community pharmacists, who have regular contact with patients, are well placed to deliver personalized inhaler education. OBJECTIVE: To determine the impact of a pharmacist intervention, informed by digital technology, on inhaler technique and adherence of patients with asthma in the community. METHODS: A cluster randomized, parallel-group, multisite pharmacy study was conducted over 6 months. All study groups had an electronic device (inhaler compliance assessment device) attached to their maintenance inhaler. A biofeedback group received personalized inhaler training informed by data recorded by the device. The demonstration group received inhaler training, by physical demonstration with a placebo inhaler. The control group received usual care. The primary outcome was inhaler adherence, which was classified as "actual adherence" and expressed as the proportion of expected drug accumulation if adherence and technique had been perfect. Secondary outcomes were quality-of-life scores as measured by the St George's Respiratory Questionnaire, symptoms, and exacerbations. RESULTS: A total of 152 participants (n = 74 biofeedback, n = 56 demonstration, and n = 22 control) were recruited. Asthma was the predominant condition among participants (n = 83), with chronic obstructive pulmonary disease (n = 55) and asthma/chronic obstructive pulmonary disease overlap also reported (n = 8). In intention-to-treat analysis, adherence in the biofeedback group during month 2 was 62%, 18% higher (95% CI, 6 to 30) than that in the demonstration group (P = .004) and 24% higher (95% CI, 9 to 40) than that in the control group (P = .003). During month 6, adherence was 14% higher (95% CI, -1 to 30; P = .07) in the biofeedback group than in the demonstration group and 31% higher (95% CI, 13 to 48; P = .001) than in the control group. At the end of the study, the biofeedback group had a sustained fall in St George's Respiratory Questionnaire from baseline, -6.1 (95% CI, -9 to -0.4; P = .04) and had significantly improved daily respiratory symptoms. CONCLUSIONS: Community pharmacist-delivered inhaler training informed by a digital technology improved adherence and health status.

Sparse coding of birdsong and receptive field structure in songbirds.

Auditory neurons can be characterized by a spectro-temporal receptive field, the kernel of a linear filter model describing the neuronal response to a stimulus. With a view to better understanding the tuning properties of these cells, the receptive fields of neurons in the zebra finch auditory fore-brain are compared to a set of artificial kernels generated under the assumption of sparseness; that is, the assumption that in the sensory pathway only a small number of neurons need be highly active at any time. The sparse kernels are calculated by finding a sparse basis for a corpus of zebra-finch songs. This calculation is complicated by the highly-structured nature of the songs and requires regularization. The sparse kernels and the receptive fields, though differing in some respects, display several significant similarities, which are described by computing quantative properties such as the seperability index and Q-factor. By comparison, an identical calculation performed on human speech recordings yields a set of kernels which exhibit widely different tuning. These findings imply that Field L neurons are specifically adapted to sparsely encode birdsong and supports the idea that sparsification may be an important element of early sensory processing.

A systematic review and meta-analysis of comparative studies comparing nonthermal versus thermal endovenous ablation in superficial venous incompetence.

OBJECTIVE: Endovenous thermal ablation (TA) offers an effective initial treatment option for superficial venous incompetence of the lower limb. These techniques offer lower complication rates with similar efficacy to traditional open surgery. In recent years, nonthermal ablation (NTA) in the form of mechanochemical ablation and cyanoacrylate vein ablation has been suggested to further reduce perioperative morbidity. This study aimed to compare the use of both thermal and nonthermal endovenous ablative techniques in the management of superficial venous incompetence. METHODS: A search of online databases including MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane database was last performed in January 2019. Comparative studies comparing NTA with TA were included. The primary outcome was technical success. Secondary outcomes included operative pain, complications, modification of disease severity, and quality of life. RESULTS: Six studies describing the outcomes of 1236 participants and 1256 truncal ablations were included for analysis. Follow-up ranged from 6 weeks to 36 months. With regard to overall technical success, 458 of 483 (94.8%) receiving NTA and 521 of 553 (94.2%) undergoing TA had successful truncal ablation on follow-up ultrasound imaging at the study end point (pooled risk ratio, 1.01; 95% confidence interval [CI], 0.99-1.04). Subgroup analysis identified no difference in success between groups during immediate, 6-month, 12-month, or >12-month follow-up periods. Postprocedural pain was generally lower in those undergoing NTA with a mean difference of -18.11 (95% CI, -36.7 to 0.48). Techniques experienced significatly lower rates of ecchymosis (risk ratio, 0.43; 95% CI, 0.23-0.78), with no difference identified with regard to rates of paresthesia, phlebitis, and skin pigmentation. Further assessment of quality of life (mean difference, -0.27; 95% CI, -0.57 to 0.04) and Venous Clinical Severity Score (-0.52; 95% CI, -1.05 to 0.01) revealed no difference between groups. Included data were deemed of moderate methodologic quality. CONCLUSIONS: Nonthermal techniques are as effective as standard TA in the first year and, in some studies, may be associated with less procedural pain. These data suggest that NTA offers an alternative and safe means to treat superficial venous disease. There is, however, a need for further powered trials with larger numbers of patients and longer follow-up to definitively examine this hypothesis.

A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages.

OBJECTIVE: We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health. METHODS: The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016. RESULTS: The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34-0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48-0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence. CONCLUSIONS: The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients' own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.

Personalising adherence-enhancing interventions using a smart inhaler in patients with COPD: an exploratory cost-effectiveness analysis.

Four inhaler adherence clusters have been identified using the INCA audio device in COPD patients: (1) regular use/good technique, (2) regular use/frequent technique errors, (3) irregular use/good technique, and (4) irregular use/frequent technique errors. Their relationship with healthcare utilization and mortality was established, but the cost-effectiveness of adherence-enhancing interventions is unknown. In this exploratory study, we aimed to estimate the potential cost-effectiveness of reaching optimal adherence in the three suboptimal adherence clusters, i.e., a theoretical shift of clusters 2, 3, and 4 to cluster 1. Cost-effectiveness was estimated over a 5-year time horizon using the Irish healthcare payer perspective. We used a previously developed COPD health-economic model that was updated with INCA trial data and Irish national economic and epidemiological data. For each cluster, interventions would result in additional quality-adjusted life years gained at reasonable investment. Cost-effectiveness was most favorable in cluster 3, with possible cost savings of €845/annum/person.

The INCATM (Inhaler Compliance AssessmentTM): A comparison with established measures of adherence.

OBJECTIVE: To compare the Inhaler Compliance AssessmentTM (INCATM), a novel audio-recording device objectively measuring timing and proficiency of inhaler use, against established adherence measures, and explore its discriminant and predictive validity. DESIGN: Prospective observational study; 184 chronic obstructive pulmonary disease (COPD) patients used an INCATM-enabled salmeterol/fluticasone inhaler for one-month post-hospital discharge. MAIN OUTCOME MEASURES: INCATM (Attempted, Attempted Interval, Actual) adherence correlated with Doses Used Rate, self-reported adherence and prescription refill for concurrent validity. Discriminant validity for reason for admission, cognition and lung function; predictive validity for health status and quality-of-life. RESULTS: Rates of Attempted, Attempted Interval and Actual adherence were 59, 47 and 23%, respectively. Only 7% of participants had Actual adherence >80%. INCATM variables significantly correlated with Doses Used Rate but not with self-report; Attempted and Attempted Interval were weakly associated with prescription refill. Higher cognitive and lung functioning groups had better INCATM adherence. Attempted and Attempted Interval predicted health status, while Doses Used Rate predicted quality-of-life. CONCLUSION: INCATM did not strongly correlate with self-report or prescription refill data. Discriminant and predictive validity demonstrated by INCATM suggests the potential utility of the INCATM as a method to identify intentional and unintentional adherence to inhaled medication and facilitate targeted intervention.