Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Burden of Disease in Patients with Mild or Mild-to-Moderate Chronic Obstructive Pulmonary Disease (Global Initiative for Chronic Obstructive Lung Disease Group A or B): A Systematic Literature Review.

Background: Patients with mild or mild-to-moderate chronic obstructive pulmonary disease (COPD), defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A/B, are regarded as having a lower risk of experiencing multiple or severe exacerbations compared with patients classified as GOLD group C/D. Current guidelines suggest that patients in GOLD A/B should commence treatment with a bronchodilator; however, some patients within this population who have a higher disease burden may benefit from earlier introduction of dual bronchodilator or inhaled corticosteroid-containing therapies. This study aimed to provide research-based insights into the burden of disease experienced by patients classified as GOLD A/B, and to identify characteristics associated with poorer outcomes. Methods: A systematic literature review (SLR) was conducted to identify evidence (burden of disease and prevalence data) relating to the population of interest (patients with COPD classified as GOLD A/B). Results: A total of 79 full-text publications and four conference abstracts were included. In general, the rates of moderate and severe exacerbations were higher among patients in GOLD group B than among those in group A. Among patients classified as GOLD A/B, the risk of exacerbation was higher in those with more symptoms (modified Medical Research Council or COPD Assessment Test scales) and more severe airflow limitation (forced expiratory volume in 1 second % predicted). Conclusion: Data from this SLR provide clear evidence of a heavier burden of disease for patients in GOLD B, compared with those in GOLD A, and highlight factors associated with worse outcomes for patients in GOLD A/B.

Disease Burden and Healthcare Utilization Among Patients with Chronic Obstructive Pulmonary Disease (COPD) in England.

Purpose: Clinical guidelines for COPD management suggest pharmacologic treatment algorithms based on symptoms and exacerbation history. As previous research has suggested that prescribing patterns are not always aligned with these recommendations, this study investigated the burden of disease in patients with COPD receiving, and persisting on, new inhaled maintenance therapy. Patients and Methods: This was a retrospective observational study using two linked electronic databases containing health records of patients in England. Patients aged ≥35 years with a confirmed diagnosis of COPD, and who initiated a new inhaled respiratory pharmacologic maintenance regimen between January 1, 2014 and December 31, 2016 (index date) were eligible for inclusion. New treatments could be long-acting muscarinic antagonist (LAMA) or long-acting ß2-agonist (LABA) monotherapy, inhaled corticosteroid (ICS)/LABA or LAMA/LABA dual therapy, or a multiple-inhaler triple therapy (MITT; LAMA/LABA/ICS). Patients were required to have 12 months of available medical history prior to, and after, the index date. Results: In total, 25,350 eligible patients were identified, of these 8282 (mean age: 70.9 years; 51.5% male) persisted with their newly prescribed inhaled therapy for ≥12 months and were included in the analysis. In the 12 months prior to index, 54% of patients had moderate or severe dyspnea (Medical Research Council score ≥3). The most common therapy initiated at index was MITT (42%), followed by ICS/LABA dual therapy (31.2%). The proportion of patients with moderate or severe dyspnea in the post-index period ranged from 29.0% of patients receiving ICS to 64.2% of patients receiving MITT. In the post-index period, 48.1% of patients experienced ≥1 exacerbation and 54.9% had ≥5 general practitioner visits. Conclusion: Many of the patients with COPD in our study continued to experience symptoms and exacerbations, despite persisting on the same treatment for ≥12 months. This suggests that some patients may benefit from treatment modification in accordance with guideline recommendations.

Validity and interpretation of spirometric recordings to diagnose COPD in UK primary care.

BACKGROUND: The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry. Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis. We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted. METHODS: Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD). We then used logistic regression to investigate predictors of correct interpretation. RESULTS: Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care. Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality. Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction. Historical records for asthma diagnosis significantly decreased odds of correct interpretation. CONCLUSION: The quality of the spirometry procedure undertaken in primary care is high. However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care. The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes.

Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUND: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002461. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Benefits of Incentives for Breastfeeding and Smoking cessation in pregnancy (BIBS): a mixed-methods study to inform trial design.

BACKGROUND: Smoking in pregnancy and/or not breastfeeding have considerable negative health outcomes for mother and baby. AIM: To understand incentive mechanisms of action for smoking cessation in pregnancy and breastfeeding, develop a taxonomy and identify promising, acceptable and feasible interventions to inform trial design. DESIGN: Evidence syntheses, primary qualitative survey, and discrete choice experiment (DCE) research using multidisciplinary, mixed methods. Two mother-and-baby groups in disadvantaged areas collaborated throughout. SETTING: UK. PARTICIPANTS: The qualitative study included 88 pregnant women/recent mothers/partners, 53 service providers, 24 experts/decision-makers and 63 conference attendees. The surveys included 1144 members of the general public and 497 health professionals. The DCE study included 320 women with a history of smoking. METHODS: (1) Evidence syntheses: incentive effectiveness (including meta-analysis and effect size estimates), delivery processes, barriers to and facilitators of smoking cessation in pregnancy and/or breastfeeding, scoping review of incentives for lifestyle behaviours; (2) qualitative research: grounded theory to understand incentive mechanisms of action and a framework approach for trial design; (3) survey: multivariable ordered logit models; (4) DCE: conditional logit regression and the log-likelihood ratio test. RESULTS: Out of 1469 smoking cessation and 5408 breastfeeding multicomponent studies identified, 23 smoking cessation and 19 breastfeeding studies were included in the review. Vouchers contingent on biochemically proven smoking cessation in pregnancy were effective, with a relative risk of 2.58 (95% confidence interval 1.63 to 4.07) compared with non-contingent incentives for participation (four studies, 344 participants). Effects continued until 3 months post partum. Inconclusive effects were found for breastfeeding incentives compared with no/smaller incentives (13 studies) but provider commitment contracts for breastfeeding show promise. Intervention intensity is a possible confounder. The acceptability of seven promising incentives was mixed. Women (for vouchers) and those with a lower level of education (except for breastfeeding incentives) were more likely to disagree. Those aged ≤ 44 years and ethnic minority groups were more likely to agree. Agreement was greatest for a free breast pump and least for vouchers for breastfeeding. Universal incentives were preferred to those targeting low-income women. Initial daily text/telephone support, a quitting pal, vouchers for > £20.00 per month and values up to £80.00 increase the likelihood of smoking cessation. Doctors disagreed with provider incentives. A 'ladder' logic model emerged through data synthesis and had face validity with service users. It combined an incentive typology and behaviour change taxonomy. Autonomy and well-being matter. Personal difficulties, emotions, socialising and attitudes of others are challenges to climbing a metaphorical 'ladder' towards smoking cessation and breastfeeding. Incentive interventions provide opportunity 'rungs' to help, including regular skilled flexible support, a pal, setting goals, monitoring and outcome verification. Individually tailored and non-judgemental continuity of care can bolster women's capabilities to succeed. Rigid, prescriptive interventions placing the onus on women to behave 'healthily' risk them feeling pressurised and failing. To avoid 'losing face', women may disengage. LIMITATIONS: Included studies were heterogeneous and of variable quality, limiting the assessment of incentive effectiveness. No cost-effectiveness data were reported. In surveys, selection bias and confounding are possible. The validity and utility of the ladder logic model requires evaluation with more diverse samples of the target population. CONCLUSIONS: Incentives provided with other tailored components show promise but reach is a concern. Formal evaluation is recommended. Collaborative service-user involvement is important. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001980. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Unintended consequences of incentive provision for behaviour change and maintenance around childbirth.

Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation.

Measuring the psychosocial burden in women with low-grade abnormal cervical cytology in the TOMBOLA trial: psychometric properties of the Process and Outcome Specific Measure (POSM).

Background: There is a need for an instrument to measure the psychosocial burden of receiving an abnormal cervical cytology result which can be used regardless of the clinical management women receive.Methods: 3331 women completed the POSM as part of baseline psychosocial assessment in a trial of management of low grade cervical cytological abnormalities. Factor analysis and reliability assessment of the POSM were conducted.Results: Two factors were extracted from the POSM: Factor 1, containing items related to worry; and Factor 2 containing items relating to satisfaction with information and support received and change in the way women felt about themselves. Factor 1 had good reliability (Cronbach's alpha 0.769), however reliability of the Factor 2 was poorer(0.482). Data collected at four subsequent time points demonstrated that the factor structure was stable over time.Conclusion: This study demonstrates the presence and reliability of a scale measuring worries within the POSM. This analysis will inform its future use in this population and in other related contexts.