Effect of 3 months and 12 months of financial incentives on 12-month postpartum smoking cessation maintenance: A randomized controlled trial.

BACKGROUND AND AIMS: Offering financial incentives is effective for smoking cessation during pregnancy. We tested the effectiveness of financial incentives for maintaining postpartum cessation, comparing 12-month and 3-month incentives with each other and with usual care (UC). DESIGN, SETTING AND PARTICIPANTS: This study was a pragmatic, multi-centre, three-arm randomized controlled trial involving four English, National Health Service, stop smoking services. A total of 462 postpartum women (aged ≥ 16 years) took part, who stopped smoking during pregnancy with financial incentives, validated as abstinent from smoking at end of pregnancy or early postpartum. INTERVENTIONS: Interventions comprised (i) UC; (ii) UC plus up to £60 of financial voucher incentives offered to participants and £60 offered to an optional significant-other supporter, over 3 months postpartum, contingent upon validated abstinence ('3-month incentives'); or (iii) UC plus '3-month incentives' plus £180 of vouchers offered to participants over 9 months postpartum, contingent upon abstinence ('12-month incentives'). MEASUREMENTS: Primary outcome: biochemically validated abstinence at 1 year postpartum. To adjust for testing all comparisons between groups with equal precision, P < 0.017 was necessary for significance. SECONDARY OUTCOMES: self-reported and validated abstinence at 3 months postpartum; self-reported abstinence at 1 year postpartum. FINDINGS: Primary outcome ascertainment: abstinence was 39.6% (63/159) 12 months incentives, 21.4% (33/154) 3 months incentives and 28.2% (42/149) UC. Adjusted odds ratios [95% confidence interval (CI)] = 12-month versus 3-month incentives OR = 2.41 (95% CI = 1.46-3.96), P = 0.001; 12 months versus UC 1.67 (1.04-2.70), P = 0.035; 3 months versus UC 0.69 (0.41-1.17), P = 0.174. Bayes factors indicated that for 12-month versus 3-month incentives and 12 months versus UC there was good evidence for the alternative hypothesis, and for 3 months versus UC there was good evidence for the null hypothesis. CONCLUSIONS: This randomized controlled trial provides weak evidence that up to £300 of voucher incentives over 12 months is effective for maintaining smoking abstinence postpartum compared with usual care. There was good evidence that 12-month incentives are superior to those over only 3 months, for which there was no evidence of effectiveness relative to usual care.

Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy.

Background: Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives: To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design: A pragmatic multi-centre randomised controlled trial. Setting: Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants: One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions: Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures: The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results: Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Limitations: Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. Conclusions: E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Future work: Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. Trial registration: This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.

Like many other smokers in the UK, some pregnant smokers try to limit or stop smoking with the help of e-cigarettes. It is not known whether this helps with stopping smoking and whether using e-cigarettes has any bad effects on the baby. We recruited 1140 pregnant smokers who wanted to quit. A random half were given nicotine patches, which are commonly used to help smokers quit. The other half were given an e-cigarette. They also received six weekly phone calls to support them in stopping smoking. We then looked at how many in each group stopped smoking by the end of pregnancy. More women stopped smoking in the group that was given an e-cigarette, but the difference was small and could be due to chance. However, some of the women in the nicotine patch group who had successfully stopped smoking were using e-cigarettes rather than patches. When these (and women in the e-cigarette group who used patches) were not counted, e-cigarettes helped almost twice as many women stop smoking than patches. E-cigarettes were better than patches in preventing low birthweight (having babies who weigh less than 2.5 kg). Otherwise, women given patches and those given e-cigarettes (and their babies) had similar numbers of medical complications. For pregnant women who smoke and need help to quit, e-cigarettes are probably more helpful than nicotine patches, and do not pose any additional risks to women or their babies.

Pediatric Psychotropic Polypharmacy: An Evaluation of the Correlates and Prevalence Across Assessment Cycles in the National Health and Nutrition Examination Survey.

Background: Pediatric psychotropic polypharmacy (PPP) is the prescription of more than one medication targeting psychiatric disorders among people younger than 18 years. Recent data suggested that PPP rates may be plateauing. Few studies have evaluated this question in large, nationally recruited samples. Objective: The National Health and Nutrition Examination Survey was used to examine the correlates and prevalence of PPP across assessment cycles. Independent assessments were obtained biannually between 2013 and 2018. Methods: Eleven thousand four hundred thirty-nine participants (4-17 years; Mage = 8.69 years; standard deviation = 5.16) were included in analyses. The Anatomic Therapeutic Chemical coding scheme was employed to classify medications, and participants were characterized as taking psychotropic medication if the medication was associated with a psychiatric diagnosis code. Participants self-reported past month medication use. Logistic regressions were used to examine correlates of pediatric psychotropic monotherapy compared with psychotropic polypharmacy. Results: Across assessments, 1.2% of respondents reported using two or more psychotropic medications. This estimate is lower than has been observed in specialized samples, but higher than other work using national samples. There was a small, significant difference in PPP across assessment cycles, such that rates of PPP were higher at the latter assessments. Correlates of PPP accorded with prior work, including male gender, increasing age, and markers of low socioeconomic status. The most robust predictor was having seen a mental health professional in the past year. Conclusions: This study documents that ∼1% of U.S. participants from a nationally recruited sample endorsed PPP. Findings are situated in the broader literature and the need for additional, prospective data to better characterize those trends in the United States and around the world. Key Takeaway Points It is known that many children and adolescents in the United States take more than one psychotropic medication, although few studies have examined trends in large, nationally recruited datasets. This study adds to this literature by documenting the prevalence of pediatric psychotropic polypharmacy in a large, unselected sample (i.e., 1.2%) and shows that rates were slightly higher at subsequent assessment intervals. Plain Language Summary Many kids take more than one medication for psychological problems. We analyzed data from ∼11,000 children and adolescents from across the United States, evaluated between 2013 and 2018. The number of kids taking multiple medications for psychological problems was different (higher) when measured later in time. Being a boy, being older, living in poverty, and having seen a mental health professional in the past year were associated with taking multiple medications for psychological problems. Implications for Managed Care Pharmacy These findings suggest rates of pediatric psychotropic polypharmacy (PPP) remain high in the United States, and correlate with male gender, poverty, and having recently seen a mental health professional. Relative to White children and adolescents, Black participants were less likely and Hispanic participants more likely to endorse PPP. Policy considerations include fully educating families and practitioners about the benefits as well as potential downsides of PPP and additional intervention options for mental health problems.

Teaching evidence-based practice: Case study of an integrated assessment task for diagnostic radiography students.

INTRODUCTION: A core competency for all health care professionals is evidence-based practice (EBP). An understanding of research skills are key to diagnostic radiographers adopting EBP, and should be taught and assessed in curricula leading to eligibility to register and practice. This paper focuses on the design, implementation and initial evaluation of an assessment task in the Diagnostic Radiography (DR) curriculum at an Australian university, which aimed to facilitate students' skills to identify and interpret research methods and output as a foundation for EBP by combining with EBP and DR theoretical content. METHODS: An integrated assessment task was introduced across two units of study, requiring student groups to produce a single literature review incorporating learning objectives from each distinct unit of study. This approach recognised and incorporated themes of student choice, negotiation of group membership, and scholarly writing as inherent components. RESULTS: Student feedback showed that students valued the integration of content knowledge and research principles across two units of study to better reflect their depth and breadth of learning. Students also commented on the value of team or group work in developing their communication and cooperation skills, which are essential skills in the DR workplace. DISCUSSION: A literature review assessment task integrated across two previously separate units of study provided an innovative approach to assessment of EBP in the DR curricula. CONCLUSION: It is anticipated that DR graduates, who are prepared with knowledge and skills in EBP prior to graduation, will become leaders and drive future innovation in EBP.

Investigating the cost-effectiveness of three cessation interventions on a national scale using the Economics of Smoking in Pregnancy (ESIP) decision analytical model.

AIM: To measure the cost-effectiveness of adding text message (TMB), exercise (EB) and abstinent-contingent financial incentive-based (CFIB) stop smoking interventions to standard smoking cessation support for pregnant women in England. DESIGN: Modelling cost-effectiveness outcomes by separately adding three cessation interventions to standard cessation care offered to pregnant women in England. English National Health Service Stop Smoking Services (NHS SSS) statistics from 2019 to 2020 were used for estimating the base quit rate. Intervention effectiveness and cost data for interventions were taken from trial reports. Cost-effectiveness was derived using the economics of smoking in pregnancy (ESIP) model from a health service and personal social services perspective. Interventions were compared with each other as well as against standard cessation care. SETTING: English NHS SSS. PARTICIPANTS/CASES: A total of 13 799 pregnant women who accessed NHS SSS. Interventions and comparator; comparator: standard stop smoking support comprising behavioural intervention and an offer of nicotine replacement therapy (NRT). Three additive interventions were TMB, EB and CFIB. MEASUREMENTS: Incremental cost-effectiveness ratios per quality-adjusted life-years gained for both mothers and offspring over their life-times; return on investment (ROI); and cost-effectiveness acceptability curves (CEACs). FINDINGS: The addition of any of the interventions compared with standard care alone was preferred, but only significant for the addition of CFIB, with the CEAC suggesting an at least 90% chance of being favoured to standard care alone. When compared against each other CFIB appeared to yield the largest returns, but this was not significant. The estimated ROI for CFIB was £2 [95% confidence interval (CI) = £1-3] in health-care savings for every £1 spent by the NHS on the cessation intervention. CONCLUSIONS: For a health system which currently provides behavioural support and an offer of nicotine replacement therapy as standard stop smoking support for pregnant women, the greatest economic gains would be provided by operating an abstinent-contingent financial incentives scheme alongside this.

Do Financial Incentives Affect Utilization for Chronically Ill Medicare Beneficiaries?

OBJECTIVE: The objective of this study was to examine the price sensitivity for provider visits among Medicare Advantage beneficiaries. DATA SOURCES: We used Medicare Advantage encounter data from 2014 to 2017 accessed as part of an evaluation for the Center for Medicare & Medicaid Innovation. STUDY DESIGN: We analyzed the effect of cost-sharing on the utilization of 2 outcome categories: number of visits (specialist and primary care) and the probability of any visit (specialist and primary care). Our main independent variable was the size of the copayment for the visit, which we regressed on the outcomes with several beneficiary-level and plan-level control variables. DATA COLLECTION/EXTRACTION METHODS: We included beneficiaries with at least 1 of 4 specific chronic conditions and matched comparison beneficiaries. We did not require beneficiaries to be continuously enrolled from 2014 to 2017, but we required a full year of data for each year they were observed. This resulted in 371,140 beneficiary-year observations. PRINCIPAL FINDINGS: Copay reductions were associated with increases in utilization, although the changes were small, with elasticities <-0.2. We also found evidence of substitution effects between primary care provider (PCP) and specialist visits, particularly cardiology and endocrinology. When PCP copays declined, visits to these specialists also declined. CONCLUSIONS: We find that individuals with chronic conditions respond to changes in copays, although these responses are small. Reductions in PCP copays lead to reduced use of some specialists, suggesting that lowering PCP copays could be an effective way to reduce the use of specialist care, a desirable outcome if specialists are overused.

Evaluating stroke early supported discharge using cost-consequence analysis.

PURPOSE: To evaluate different stroke early supported discharge (ESD) services in different geographical settings using cost-consequence analysis (CCA), which presents information about costs and outcomes in the form of a balance sheet. ESD is a multidisciplinary service intervention that facilitates discharge from hospital and includes delivery of stroke specialist rehabilitation at home. MATERIALS AND METHODS: Data were collected from six purposively sampled services across the Midlands, East and North of England. All services, rural and urban, provided stroke rehabilitation to patients in their own homes. Cost data included direct and overhead costs of service provision and staff travel. Consequence data included service level adherence to an expert consensus regarding the specification of ESD service provision. RESULTS: We observed that the most rural services had the highest service cost per patient. The main costs associated with running each ESD service were staff costs. In terms of the consequences, there was a positive association between service costs per patient and greater adherence to meeting the evidence-based ESD service specification agreed by an expert panel. CONCLUSIONS: This study found that rural services were associated with higher costs per patient, which in turn were associated with greater adherence to the expert consensus regarding ESD service specification. We suggest additional resources and costs are required in order for rural services to meet evidence-based criteria.Implications for rehabilitationThe main costs of an early supported discharge (ESD) service for stroke survivors were staff costs and these were positively associated with greater levels of rurality.Greater costs were associated with greater adherence to ESD core components, which has been previously found to enhance the effectiveness of ESD service provision.The cost-consequence analysis provides a descriptive summary for decision-makers about the costs of delivering ESD, suggesting additional resources and costs are required in order for rural services to meet evidence-based criteria.

Invasive Mycobacterium abscessus Complex Infection After Cardiac Surgery: Epidemiology, Management, and Clinical Outcomes.

BACKGROUND: We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. METHODS: We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. RESULTS: Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38-139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5-33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. CONCLUSIONS: Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.

Understanding policy change for obesity prevention: learning from sugar-sweetened beverages taxes in Mexico and Chile.

This article examines the policy change process that resulted in the current sugar-sweetened beverages taxes in Mexico and Chile, using the Kaleidoscope Model for Policy Change, a framework developed for nutrition and food policy change analysis. We used a qualitative study design, including 24 key informant (KI) interviews (16 researchers, 5 civil society representatives and 3 food/beverage industry representatives), encompassing global and in-country perspectives. The analysis shows concurrence with the Kaleidoscope Model, highlighting commonalities in the policy change process. These included the importance of focusing events and coalitions for agenda-setting. Both top-down executive leadership and bottom-up pressure from civil society coalitions were important for the policy adoption as were flexible framing of the tax, and taking advantage of windows of opportunity. In both countries, the tax resulted from national, revenue-seeking fiscal reforms and in sub-optimal tax rates, as a result of the industry influence. KIs also discussed emerging evaluation results, highlighting differences in interpretation concerning the magnitude of change from the tax, and shared potential modifications to the current policies. This analysis contributes to a greater understanding of the policy change process focused on obesity prevention, using an innovative theoretical framework developed specifically for food and nutrition policy.

Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT.

BACKGROUND: Relapse remains an unresolved issue in smoking cessation. Extended stop smoking medication use can help, but uptake is low and several behavioural relapse prevention interventions have been found to be ineffective. However, opportunistic 'emergency' use of fast-acting nicotine replacement treatment or electronic cigarettes may be more attractive and effective, and an online behavioural Structured Planning and Prompting Protocol has shown promise. The present trial aimed to evaluate the clinical effectiveness and cost-effectiveness of these two interventions. DESIGN: A randomised controlled trial. SETTING: English stop smoking services and Australian quitlines, Australian social media and St Vincent's Hospital Melbourne, Fitzroy, VIC. PARTICIPANTS: Ex-smokers abstinent for at least 4 weeks, with some participants in Australia also recruited from 1 week post quit date. The planned sample size was 1400, but the trial was curtailed when 235 participants were recruited. INTERVENTIONS: Participants were randomised in permuted blocks of random sizes to (1) oral nicotine replacement treatment/electronic cigarettes to use if at risk of relapse, plus static text messages (n = 60), (2) the Structured Planning and Prompting Protocol and interactive text messages (n = 57), (3) oral nicotine replacement treatment/electronic cigarettes plus the Structured Planning and Prompting Protocol with interactive text messages (n = 58) or (4) usual care plus static text messages (n = 59). OUTCOME MEASURES: Owing to delays in study set-up and recruitment issues, the study was curtailed and the primary outcome was revised. The original objective was to determine whether or not the two interventions, together or separately, reduced relapse rates at 12 months compared with usual care. The revised primary objective was to determine whether or not number of interventions received (i.e. none, one or two) affects relapse rate at 6 months (not biochemically validated because of study curtailment). Relapse was defined as smoking on at least 7 consecutive days, or any smoking in the last month at final follow-up for both the original and curtailed outcomes. Participants with missing outcome data were included as smokers. Secondary outcomes included sustained abstinence (i.e. no more than five cigarettes smoked over the 6 months), nicotine product preferences (e.g. electronic cigarettes or nicotine replacement treatment) and Structured Planning and Prompting Protocol coping strategies used. Two substudies assessed reactions to interventions quantitatively and qualitatively. The trial statistician remained blinded until analysis was complete. RESULTS: The 6-month relapse rates were 60.0%, 43.5% and 49.2% in the usual-care arm, one-intervention arm and the two-intervention arm, respectively (p = 0.11). Sustained abstinence rates were 41.7%, 54.8% and 50.9%, respectively (p = 0.17). Electronic cigarettes were chosen more frequently than nicotine replacement treatment in Australia (71.1% vs. 29.0%; p = 0.001), but not in England (54.0% vs. 46.0%; p = 0.57). Of participants allocated to nicotine products, 23.1% were using them daily at 6 months. The online intervention received positive ratings from 63% of participants at 6 months, but the majority of participants (72%) completed one assessment only. Coping strategies taught in the Structured Planning and Prompting Protocol were used with similar frequency in all study arms, suggesting that these are strategies people had already acquired. Only one participant used the interactive texting, and interactive and static messages received virtually identical ratings. LIMITATIONS: The inability to recruit sufficient participants resulted in a lack of power to detect clinically relevant differences. Self-reported abstinence was not biochemically validated in the curtailed trial, and the ecological momentary assessment substudy was perceived by some as an intervention. CONCLUSIONS: Recruiting recent ex-smokers into an interventional study proved problematic. Both interventions were well received and safe. Combining the interventions did not surpass the effects of each intervention alone. There was a trend in favour of single interventions reducing relapse, but it did not reach significance and there are reasons to interpret the trend with caution. FUTURE WORK: Further studies of both interventions are warranted, using simpler study designs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11111428. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 68. See the NIHR Journals Library website for further project information. Funding was also provided by the National Health and Medical Research Council, Canberra, ACT, Australia (NHMRC APP1095880). Public Health England provided the funds to purchase the nicotine products in England.

Stop smoking services help people to stop smoking over a short period of time. However, nearly three-quarters of quitters return to smoking (i.e. relapse) within 1 year. Effective relapse prevention strategies are needed. Traditional behavioural relapse prevention strategies (e.g. teaching techniques to resist having a cigarette) have not proved effective. However, an earlier study showed that an online programme guiding smokers in stopping smoking and remaining abstinent reduced relapse between 1 week and 6 months. Long-term use of stop smoking medications (e.g. nicotine replacement treatment) can also help, but most successful quitters do not continue to use them. Nicotine mouth spray, lozenges or electronic cigarettes that can quickly help relieve urges to smoke and that ex-smokers can use 'in emergencies' could be a more attractive option. We planned to test these two interventions, on their own and together, in 1400 participants who had quit ≥ 4 weeks previously and who were recruited from English stop smoking services and Australian quitlines. We would then compare these participants with the participants following usual care (i.e. access to stop smoking medications used during the quit attempt for up to 3 months). Owing to delays in study set-up and difficulties in recruiting, the study recruited only 234 participants (n = 131 in Australia and n = 103 in England). We studied participants' reactions to the two interventions and to their combination, and how clinically effective the interventions were. Both interventions were rated positively by most participants. Among the participants in Australia, electronic cigarettes were more popular than medical nicotine products. In England, both products were equally popular. Participants in the online intervention group appreciated the advice on coping strategies, but they rarely completed repeat assessments. In addition, participants who were not in this group used the strategies just as much. There were hints that the interventions may be helpful in preventing relapse. There is an indication that the two interventions combined did not do any better than each on its own, but this requires replication in a larger study. Although the interventions show promise, the small number of participants recruited means that we are unable to make strong conclusions. The study identified areas for future work.

Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial.

Importance: Micro-dystrophin gene transfer shows promise for treating patients with Duchenne muscular dystrophy (DMD) using recombinant adeno-associated virus serotype rh74 (rAAVrh74) and codon-optimized human micro-dystrophin driven by a skeletal and cardiac muscle-specific promoter with enhanced cardiac expression (MHCK7). Objective: To identify the 1-year safety and tolerability of intravenous rAAVrh74.MHCK7.micro-dystrophin in patients with DMD. Design, Setting, and Participants: This open-label, phase 1/2a nonrandomized controlled trial was conducted at the Nationwide Children's Hospital in Columbus, Ohio. It began on November 2, 2017, with a planned duration of follow-up of 3 years, ending in March 2021. The first 4 patients who met eligibility criteria were enrolled, consisting of ambulatory male children with DMD without preexisting AAVrh74 antibodies and a stable corticosteroid dose (≥12 weeks). Interventions: A single dose of 2.0 × 1014 vg/kg rAAVrh74.MHCK7.micro-dystrophin was infused through a peripheral limb vein. Daily prednisolone, 1 mg/kg, started 1 day before gene delivery (30-day taper after infusion). Main Outcomes and Measures: Safety was the primary outcome. Secondary outcomes included micro-dystrophin expression by Western blot and immunohistochemistry. Functional outcomes measured by North Star Ambulatory Assessment (NSAA) and serum creatine kinase were exploratory outcomes. Results: Four patients were included (mean [SD] age at enrollment, 4.8 [1.0] years). All adverse events (n = 53) were considered mild (33 [62%]) or moderate (20 [38%]), and no serious adverse events occurred. Eighteen adverse events were considered treatment related, the most common of which was vomiting (9 of 18 events [50%]). Three patients had transiently elevated γ-glutamyltransferase, which resolved with corticosteroids. At 12 weeks, immunohistochemistry of gastrocnemius muscle biopsy specimens revealed robust transgene expression in all patients, with a mean of 81.2% of muscle fibers expressing micro-dystrophin with a mean intensity of 96% at the sarcolemma. Western blot showed a mean expression of 74.3% without fat or fibrosis adjustment and 95.8% with adjustment. All patients had confirmed vector transduction and showed functional improvement of NSAA scores and reduced creatine kinase levels (posttreatment vs baseline) that were maintained for 1 year. Conclusions and Relevance: This trial showed rAAVrh74.MHCK7.micro-dystrophin to be well tolerated and have minimal adverse events; the safe delivery of micro-dystrophin transgene; the robust expression and correct localization of micro-dystrophin protein; and improvements in creatine kinase levels and NSAA scores. These findings suggest that rAAVrh74.MHCK7.micro-dystrophin can provide functional improvement that is greater than that observed under standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT03375164.

Is digital health care more equitable? The framing of health inequalities within England's digital health policy 2010-2017.

Informed by a discourse analysis, this article examines the framing of equity within the UK's digital health policies between 2010 and 2017, focusing on England's development of NHS Digital and its situation within the UK Government's wider digital strategy. Analysis of significant policy documents reveals three interrelated discourses that are engaged within England's digital health policies: equity as a neoliberal imaginary of digital efficiency and empowerment; digital health as a pathway towards democratising health care through data-sharing, co-creation and collaboration; and finally, digital health as a route towards extending citizen autonomy through their access to data systems. It advances knowledge of the relationship between digital health policy and health inequalities. Revealing that while inclusion remains a priority area for policymakers, equity is being constituted in ways that reflect broader discourses of neoliberalism, empowerment and the turn to the market for technological solutionism, which may potentially exacerbate health inequalities.

Does cost feedback modify demand for common blood tests in secondary care? A prospective controlled intervention study.

BACKGROUND: Behavioural insights or 'nudge' theory suggests that non-directional interventions may be used to modify human behaviour. We have tested the hypothesis that the provision of the cost of common blood tests with their results may modify subsequent demand for blood assays. METHODS: The study design was a prospective controlled intervention study. The individual and annual institutional cost of full blood count (FBC), urea and electrolytes (U&E) and liver function test (LFT) blood assays were added to the electronic results system for inpatients at the intervention teaching hospital, but not the control hospital. RESULTS: In the 12 months after the intervention was implemented, demand for FBC dropped by 3% (95% confidence interval (CI) 1-5; p<0.001), U&E by 2% (95% CI 0-4; p=0.054) and there was no change in demand for LFT compared to the control institution. CONCLUSIONS: Providing cost feedback to clinicians for commonly used blood tests is a viable intervention that is associated with small reductions in demand for some, but not all blood assays. As this is an easily scalable approach, this has potential to enable efficient healthcare delivery, while also minimising the morbidity experienced by the patient.

Incorporating Social Determinants of Health in Electronic Health Records: Qualitative Study of Current Practices Among Top Vendors.

BACKGROUND: Social determinants of health (SDH) are increasingly seen as important to understanding patient health and identifying appropriate interventions to improve health outcomes in what is a complex interplay between health system-, community-, and individual-level factors. OBJECTIVE: The objective of the paper was to investigate the development of electronic health record (EHR) software products that allow health care providers to identify and address patients' SDH in health care settings. METHODS: We conducted interviews with six EHR vendors with large market shares in both ambulatory and inpatient settings. We conducted thematic analysis of the interviews to (1) identify their motivations to develop such software products, (2) describe their products and uses, and (3) identify facilitators and challenges to collection and use of SDH data-through their products or otherwise-either at the point of care or in population health interventions. RESULTS: Our findings indicate that vendor systems and their functionalities are influenced by client demand and initiative, federal initiatives, and the vendors' strategic vision about opportunities in the health care system. Among the small sample of vendors with large market shares, SDH is a new area for growth, and the vendors range in the number and sophistication of their SDH-related products. To enable better data analytics, population health management, and interoperability of SDH data, vendors recognized the need for more standardization of SDH performance measures across various federal and state programs, better mapping of SDH measures to multiple types of codes, and development of more codes for all SDH measures of interest. CONCLUSIONS: Vendors indicate they are actively developing products to facilitate the collection and use of SDH data for their clients and are seeking solutions to data standardization and interoperability challenges through internal product decisions and collaboration with policymakers. Due to a lack of policy standards around SDH data, product-specific decisions may end up being de facto policies given the market shares of particular vendors. However, commercial vendors appear ready to collaboratively discuss policy solutions such as standards or guidelines with each other, health care systems, and government agencies in order to further promote integration of SDH data into the standard of care for all health systems.

Toward Improving Breast Cancer Imaging: Radiological Assessment of Propagation-Based Phase-Contrast CT Technology.

RATIONALE AND OBJECTIVES: This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography. MATERIALS AND METHODS: Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments. RESULTS: The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores. CONCLUSION: The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging.

A dynamic, modifiable model for estimating cost-effectiveness of smoking cessation interventions in pregnancy: application to an RCT of self-help delivered by text message.

BACKGROUND AND AIMS: Previous evaluations of smoking cessation interventions in pregnancy have several limitations. Our solution to these limitations is the Economics of Smoking in Pregnancy (ESIP) model, which estimates the life-time cost-effectiveness of smoking cessation interventions in pregnancy from a National Health Service (NHS) and personal social services perspective. We aim to (1) describe how ESIP has been constructed and (2) illustrate its use with trial data. METHODS: ESIP links mothers' and offspring pregnancy outcomes to estimate the burdens of smoking-related disease they experience with different rates of smoking in pregnancy, both in pregnancy and throughout their life-times. Smoking rates are inputted by model users. ESIP then estimates the costs of treating disease burdens and also mothers' and offspring life-years and quality-adjusted life years (QALYs). By comparing costs incurred and healthy life following different smoking rates, ESIP estimates incremental cost-effectiveness and benefit-cost ratios for mothers or offspring or both combined. We illustrate ESIP use using data from a pragmatic randomized controlled trial that tested a smoking cessation intervention in pregnancy. RESULTS: Throughout women's and offspring life-times, the intervention proved cheaper than usual care, having a negative incremental cost of £38.37 (interquartile range = £21.46-56.96) and it improved health, demonstrating a 0.04 increase in incremental QALYs for mothers and offspring, implying that it is 'dominant' over usual care. Benefit-cost ratios suggested that every £1 spent would generate a median of £14 (interquartile range = £8-20) in health-care savings. CONCLUSIONS: Economics of Smoking in Pregnancy is the first economic model to link mothers' and infants' costs and benefits while reporting cost-effectiveness in readily-comparable units. Using ESIP with data from a trial which reported only short-term economic analysis showed that the intervention was very likely to be cost-effective in the longer term and to generate health-care savings.

Cost-effectiveness of a complex intervention to reduce children's exposure to second-hand smoke in the home.

BACKGROUND: Second-hand smoke (SHS) causes numerous health problems in children such as asthma, respiratory tract infections and sudden infant death syndrome. The home is the main source of exposure to SHS for children, particularly for young children. We estimated the cost-effectiveness of a complex intervention designed to reduce SHS exposure of children whose primary caregiver feels unable or unwilling to quit smoking. METHODS: A cost-effectiveness analysis was carried out alongside an open-label, parallel, randomised controlled trial in deprived communities in Nottingham, England. A complex intervention combining behavioural support, nicotine replacement therapy and personalised feedback on home air quality was compared with usual care. A total number of 205 households were recruited, where the main caregivers were aged 18 and over, with a child aged under five years living in their household reporting smoking inside their home. Analyses for this study were undertaken from the National Health Service/Personal Social Services perspective. All costs were estimated in UK pounds (£) at 2013/14 prices. The primary outcome was the incremental cost-effectiveness of change in air quality in the home, measured as average 16-24 h levels of particulate matter of < 2.5 µm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included incremental cost per quitter, quit attempts and cigarette consumption in the home. A non-parametric bootstrap re-sampling technique was employed to explore uncertainty around the calculated incremental cost-effectiveness ratios. RESULTS: The complex intervention achieved reduced PM2.5 by 21.6 µg/m3 (95% CI: 5.4 to 37.9), with an incremental cost of £283 (95% CI: £254-£313), relative to usual care. The incremental cost-effectiveness ratio was £131 (bootstrapped 95% CI: £72-£467) per additional 10µg/m3 reduction in PM2.5, or £71 (bootstrapped 95% CI: -£57-£309) per additional quitter. CONCLUSIONS: This trial targeted a socio-economically disadvantaged population that has been neglected within the literature. The complex intervention was more costly but more effective in reducing PM2.5 compared with the usual care. It offers huge potential to reduce children's' tobacco-related harm by reducing exposure to SHS in the home. The intervention is considered cost-effective if the decision maker is willing to pay £131 per additional 10µg/m3 of PM2.5 reduction. TRIAL REGISTRATION: The Smoke Free Homes trial was registered with isrctn.com on 29 January 2013 with the identifier ISRCTN81701383 .

Inaugural HealthAccord Conference (SportAccord Convention, Bangkok, Thailand): The Power of Sport - The Power to Change.

SportAccord organized the inaugural HealthAccord conference on April 19, 2018, in Bangkok, Thailand. The goal of HealthAccord is for the International Sport Federations (IF) and sport industry leaders to address high-priority issues facing sport through a serious commitment to innovation to protect athlete health, to enhance athlete performance, and to stimulate action to improve global health through the promotion of physical activity. The first HeathAccord conference was organized by drawing on the knowledge and experience of experts from global health programs focused on athletes and global citizens, respectively. The first session, "The Power of Sport," addressed the application of "state of the art" sport science and sport medicine for the protection of athlete health and to enhance sport performance. "The Power of Sport" session concentrated on enabling athletes to perform spectacular feats that are "higher, stronger, faster" intended to engage and thrill global audiences without resorting to prohibited substances and methods, to enable athletes to remain active in sport for a longer career, and to increase the attraction of sport for sponsors. In the second session, "The Power to Change," sport was viewed as having an important role in promoting physical activity within their respective federations, community, and internationally. The Olympic movement, IF, and other sport stakeholders are urgently needed to become the social drivers to correct the mismatch between physical activity for health development and draw toward sedentary lifestyles of the modern world. Key outcomes of this first HealthAccord conference were the agreement among participants to develop an innovative and high-impact collaboration between IF and related stakeholders; to use sport as a social movement platform to measurably improve health, both for athletes and for global citizens.

Nicotine preloading for smoking cessation: the Preloading RCT.

BACKGROUND: Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data. OBJECTIVES: To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading. DESIGN: Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis. SETTING: NHS smoking cessation clinics. PARTICIPANTS: People seeking help to stop smoking. INTERVENTIONS: Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators. MAIN OUTCOME MEASURES: The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model. RESULTS: In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) -0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI -£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving. LIMITATIONS: The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified. CONCLUSIONS: Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33031001. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.