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4. Discussion and conclusions
|
obese
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OBESE
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In the present study, we investigated whether near-infrared venous imaging or ultrasound guidance facilitates novices in obtaining difficult peripheral venous access using a simulated vein. The results show that obtaining difficult vascular access with near-infrared venous imaging was faster than when using ultrasound guidance, with no difference in success rate or proficiency using the technique. The simulator used in this study (a difficult venous access simulator) was designed to mimic the conditions under which veins are invisible to the naked eye, similar to the situation in some obese patients. The authors believe that near-infrared venous imaging may be useful for securing peripheral venous access in obese patients. Near-infrared venous imaging also has the advantage of requiring less training than ultrasound guidance.Near-infrared venous imaging was expected to improve the success rate for obtaining peripheral venous access in children.Recently, Yalçinli et al compared near-infrared venous imaging, ultrasound guidance, and conventional methods in adult patients and found that ultrasound guidance had a higher initial attempt success rate than near-infrared venous imaging or conventional methods.Cannulating veins using ultrasound guidance requires appropriate training and improves with experience. However, no consensus of a clear goal for technical skills acquisition has been established. In the present study, the simulation training given to participating medical students had the same content as preclinical basic training for residents.Ultrasound guidance has a great advantage over near-infrared venous imaging in that it can identify deeper veins. Near-infrared venous imaging has a limitation in its ability to locate deep veins, which cannot be observed over 5 mm deep. For this reason, ultrasound guidance is more clinically useful than near-infrared venous imaging. However, appropriate education is critical for this purpose. Near-infrared venous imaging may be useful as a method that requires less education and a useful way for novices to gain experience.Many studies have evaluated the teaching methods used for ultrasound guided venous access, but there is still no method accepted as the optimal approach.
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PMC10036034
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Acknowledgments
|
The authors thank Ms. Okada (Laboratory assistant, Division of Biological Function Research) for her assistance.
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PMC10036034
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References
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PMC10036034
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Background
|
infections
|
INFECTIONS
|
The authors have declared that no competing interests exist.Fishing exposes fishermen to schistosomiasis-infested fresh water and concurrently through precarious livelihoods to risky sexual behaviour, rendering these two infections occupational hazards for fishermen. This study aimed to characterize the knowledge of the two conditions to obtain necessary data for a subsequent cluster randomized trial designed to investigate demand creation strategies for joint HIV-schistosomiasis service provision in fishing villages on the shores of southern Lake Malawi.
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PMC10187898
|
Methods
|
HIV and schistosomiasis
|
REGRESSION
|
Enumeration of all resident fishermen in 45 clusters (fishing communities) was carried out between November 2019 and February 2020. In a baseline survey, fishermen reported their knowledge, attitudes and practices in the uptake of HIV and schistosomiasis services. Knowledge of HIV status and previous receipt of praziquantel were modelled using random effects binomial regression, accounting for clustering. Prevalence of willingness to attend a beach clinic was computed.
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PMC10187898
|
Results
|
HIV and schistosomiasis
|
A total of 6,297 fishermen were surveyed from the 45 clusters with harmonic mean number of fishermen per cluster of 112 (95% CI: 97; 134). The mean age was 31.7y (SD: 11.9) and nearly 40% (2,474/6,297) could not read or write. Overall, 1,334/6,293 (21.2%) had never tested for HIV, with 64.4% (3,191/4,956) having tested in the last 12 months, and 5.9% (373/6290) taking antiretroviral therapy (ART). In adjusted analyses, being able to read and write (adjusted risk ratio [aRR: 1.91, 95% CI: 1.59–2.29, p<0.001); previous use of praziquantel (aRR: 2.00,95% CI: 1.73–2.30, p<0.001); knowing a relative or friend who died of HIV (aRR: 1.54,95% CI: 1.33–1.79, p<0.001); and being on ART (aRR: 12.93, 95% CI: 6.25–32.93, p<0.001) were associated with increased likelihood of ever testing for HIV. Only 40% (1,733/4,465) had received praziquantel in the last 12 months. Every additional year of age was associated with 1% decreased likelihood of having taken praziquantel in the last 12 months (aRR: 0.99, 95% CI: 0.98–0.99, p<0.001). However, recent HIV testing increased the likelihood of taking praziquantel by over 2-fold (aRR 2.24, 95% CI: 1.93–2.62, p<0.001). Willingness to attend a mobile beach clinic offering integrated HIV and schistosomiasis services was extremely high at 99.0% (6,224/6,284).
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PMC10187898
|
|
Conclusion
|
HIV and schistosomiasis
|
SCHISTOSOMIASIS
|
In a setting with an underlying high prevalence of both HIV and schistosomiasis, we found low knowledge of HIV status and low utilization of free schistosomiasis treatment. Among fishermen who accessed HIV services, there was a very high likelihood of taking praziquantel suggesting that integrated service delivery may lead to good coverage.
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PMC10187898
|
Trial registration
|
This trial is registered in the ISRCTN registry:
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PMC10187898
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Author summary
|
schistosomiasis
|
SCHISTOSOMIASIS
|
Both HIV and schistosomiasis (bilharzia) remain public health threats especially in fishing communities along the Great Rift Valley in Africa. HIV remains generalized in fishing communities with up to 20% of fishing communities living with HIV. Similarly, although schistosomiasis is
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PMC10187898
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Data Availability
|
Data is available via the
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PMC10187898
|
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Introduction
|
HIV and schistosomiasis, HIV and human schistosomiasis, alcoholism
|
DISEASES, SCHISTOSOMIASIS
|
HIV and human schistosomiasis prevalence remain unacceptably high along the Great Rift Valley in Africa especially on lakeshores, due in part to complex behavioural patterns including fish-for-sex exchanges, alcoholism, condomless sex and poor access to health services[As well as strong geographical correlation between HIV and schistosomiasis prevalence in many African countries, there are strong bidirectional assocations between the two diseases at the individual level[The “creating demand for fishermen’s schistosomiasis and HIV services (FISH)” cluster-randomized trial (CRT) aims to deliver HIV testing–including oral HIV self-testing (HIVST)–and
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PMC10187898
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Methods
|
PMC10187898
|
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Ethics statement
|
The FISH CRT is registered in the ISRCTN registry, number ISRCTN14354324 accessible at
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PMC10187898
|
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Study design
|
This was a cross-sectional baseline survey conducted between November 2019 and February 2020 prior to the implementation of a community cluster-randomized trial (CRT) [
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PMC10187898
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Setting
|
Preceding the baseline survey we undertook a formative social and physical mapping exercise on the shores of Mangochi, a district in the southeastern region of Malawi which borders Lake Malawi and Mozambique. On the southern lakeshore of Malawi, fishing is predominantly undertaken by men through small boats of up to 10 fishermen. We defined clusters to be landing sites, i.e. fishing communities on the lakeshore. Fishing communities were located using Google Earth maps together with local residents, and circumferential walks with global positioning satellite (GPS) devices were done to demarcate trial cluster boundaries. Community and peer leaders (fishermen representatives) were engaged to agree on the cluster boundaries, and to introduce the baseline survey and the subsequent CRT.
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PMC10187898
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Participants and procedures
|
The baseline survey set out to investigate knowledge, attitudes and previous testing and treatment behaviour of fishermen in southern Malawi fishing communities. Within each cluster peer leaders provided a list of fishing boats operating in the cluster as well as a list of fishermen operating in the listed boats. To be eligible for the survey, fishermen needed to: be 18 years old or over; have a fixed residence in a trial cluster; and consent to participate. We excluded fishermen who were not permanent residents of the fishing community or were underage (<18y).Fishermen completed a face-to-face interview on tablets running open data kit (ODK) questionnaires. A total of seven interviewers were involved in the data collection. The interviewers were selected on the basis of being from within the Mangochi district to ensure quality of responses due to familiarity with the local dialect spoken in this part of the district. Interviews were conducted on the lakeshore at a private space chosen by the fishermen. All outcomes were measured via self-reports by the fishermen.
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PMC10187898
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Outcomes
|
HIV and schistosomiasis, HIV and schistosomiaisis
|
Three main fisherman-level outcomes were examined in this analysis: proportion reported to have ever tested for HIV; proportion reported having tested for HIV in the last 12 months; and proportion who reported having taken praziquantel in the preceding 12 months. Explanatory variables included: age, literacy; educational attainment; male circumcision status; self-rated general health status; and knowing someone who died of HIV. Knowledge of HIV status was examined as an explanatory variable for the taking praziquantel outcome and vice versa, being indicative of health-seeking behaviour by the participant. We additionally investigated fishermens’ willingness to attend a beach clinic offering free integrated HIV and schistosomiasis services, measured by asking “Would you be wiling to attend a beach clinic offering both HIV and schistosomiaisis services?”
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PMC10187898
|
|
Statistical methods
|
The sample size for the survey was determined by the total number of fishermen in the clusters of the CRT. Assuming conservatively that 44% of fishermen had never tested for HIV[Analysis used R version 4.1.3 (R Core Data Team[
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PMC10187898
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Results
|
A total of 6,297 participants in 45 clusters completed the baseline survey. The harmonic mean cluster size was 112 fishermen (range: 34; 245). Mean age of fishermen was 31.7 (SD: 11.9) years, with married individuals accounting for 3,924 (62.4%) (
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PMC10187898
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Demographic characteristics.
|
therapyMissing, HIV or schistosomiasis separately or combined.
|
SCHISTOSOMIASIS
|
SD: standard deviation; MSCE: Malawi school certificate of education; ART: antiretroviral therapyMissing values, denominator = 6,297: age 3(0.05%); marital status 6 (0.10%); literacy 5 (0.08%); education level 4 (0.06%); tested for HIV before 4 (0.06%); tested for HIV in the last 12 months 4 (0.06%); currently on ART 7 (0.11%); circumcision status 6 (0.10%); ever taken praziquantel 9 (0.14%); taken praziquantel in the last 12 months 9 (0.14%); know friend or relative who died of HIV 270 (4.29%); self-rated general health 3 (0.05%); willingness to attend beach clinic offering HIV services 8 (0.13%); willingness to attend beach clinic offering schistosomiasis services 13 (0.21%); willingness to attend beach clinic offering both HIV and schistosomiasis services 13 (0.21%).Most partcipants (4,959, 78.8%) reported that they had previously tested for HIV; 373 (5.9%) reported taking antiretroviral therapy (ART). Overall, 71.1% (4,472) reported having taken praziquantel for schistosomiasis, with only 38.8% (n = 1,733) receiving a treatment course in the preceding 12 months. Overall, most (99%, 6224/6297) of the participants reported they would be willing to attend a beach clinic offering services for HIV or schistosomiasis separately or combined.There was considerable variation in the reported lifetime testing for HIV across the 45 clusters (
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PMC10187898
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Unadjusted and adjusted associations with HIV testing in the last 12 months.
|
aRR: adjusted risk ratio; CI: confidence interval; MSCE: Malawi school certificate of education; ART: antiretroviral therapyrho (The overall harmonic mean prevalence of reported praziquantel use in the last 12 months was 33.9% (95% CI: 30.4%; 38.4%) with notable variation (
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PMC10187898
|
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Spatial distribution of antiretroviral therapy use, circumcision, and previous praziquantel use among fishermen across study clusters.
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PMC10187898
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Unadjusted and adjusted associations with taking schistosomiasis treatment in the last 12 months.
|
aRR: adjusted risk ratio; CI: confidence interval; MSCE: Malawi school certificate of educationrho (Willingness to attend a beach clinic offering both HIV and schistosomiasis testing was extremely high with 99.0% of indicating they would visit such a clinic (6,224/6297) (The variation in lifetime and recent (within last 12 months) HIV testing history revealed that most of the 45 clusters had a higher proportion threshold of over 80% of fishermen who have ever tested for HIV. In addition, two fishermen clusters (28,29) had proportions of ever tested for HIV below 70% while cluster one and 14 had their proportion peaks above 90% (As reported in The spatial distribution of Praziquantel among the fishing communities living along the shores of Lake Malawi indicating variation in prevalence from less than 10% to more than 50% (
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PMC10187898
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Discussion
|
PMC10187898
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Key results
|
HIV and schistosomiasis
|
SCHISTOSOMIASIS
|
The main findings from this study included low utilization of free HIV services and schistosomiasis treatment (Praziquantel) among a high risk population of fishermen on the shores of Lake Malawi, (indicating that service integration is likely to increase uptake of both services), and extremely high willingness to attend beach clinics. The literature identifies mobility among fishermen, inconvenient offer of health services where there is mistiming, long distances to health facilities and stigma as key factors that contribute to low utilization[The recent data from the Malawi population-based HIV impact assessment (MPHIA) indicate that 12% of people living with HIV in Malawi are not aware of their HIV status [Malawi implements twice a year mass drug administration of praziquantel among the fishing communities[Contrary to the strongly held opinion that fishermen are unwilling to utilize health services, we found extremely high willingness to attend a mobile beach clinic when offered hypothetically among the surveyed fishermen. The key difference was that we made it clear that such a beach clinic would firstly be made available right on the lakeshore to provide convenience and secondly that fishermen would be able to access it during a wide range of hours. Such a flexible approach in service delivery has been shown in various studies and programmes to increase the uptake of services dramatically, especially for men[The main strength of this study is that we showed promising results on potential significant uptake of integrated HIV and schistosomiasis services among the fishing population in Mangochi, Malawi as this will inform demand creation efforts.The main limitation of this study was that it gives a snapshot of the baseline prevalence of the two hazards, but does not measure the impact of the services being rendered in the beach clinics. Self-reporting of HIV testing and uptake of the schistosomiasis drug praziquantel might have contributed to information bias. Given that all outcomes were self-reported there is likelihood of information bias. HIV and schistosomiasis services are free of charge and fishermen know that they are a priority population. Thus, social desirability bias would have been likely whereby fishermen may have reported that they tested for HIV or took Praziquantel when in fact they had not done so. For both HIV and schistosomiasis, distance to the nearest health facility may be an important factor which was not included in the data reported here.The study findings are generalizable to Malawi fishermen over 18 years of age and the large sample size was critical in reducing random errors. However, following this baseline study, there will be a cluster-randomized trial which will enhance both the internal and external validity of the study outcomes.
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PMC10187898
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Conclusions
|
HIV and Schistosomiasis, HIV and schistosomiasis
|
SCHISTOSOMIASIS
|
In summary, we found that fishermen who accessed HIV services had a high likelihood of having previously taken the schistosomiasis drug praziquantel providing evidence that integrated service delivery may lead to increase coverage. We observed that populations in settings with a high prevalence of both HIV and schistosomiasis had low knowledge of their HIV status and low utilization of free schistosomiasis treatment. Nearly 99% of fishermen studied expressed willingness to receive both HIV and Schistosomiasis services if a mobile beach clinic is made available.
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PMC10187898
|
References
|
PMC10187898
|
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PURPOSE
|
cancer
|
CANCER
|
Few cancer centers systematically engage patients with evidence-based tobacco treatment despite its positive effect on quality of life and survival. Implementation strategies directed at patients, clinicians, or both may increase tobacco use treatment (TUT) within oncology.
|
PMC10552951
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METHODS
|
cancer
|
CANCER
|
We conducted a four-arm cluster-randomized pragmatic trial across 11 clinical sites comparing the effect of strategies informed by behavioral economics on TUT engagement during oncology encounters with cancer patients. We delivered electronic health record (EHR)–based nudges promoting TUT across four nudge conditions: patient only, clinician only, patient and clinician, or usual care. Nudges were designed to counteract cognitive biases that reduce TUT engagement. The primary outcome was TUT penetration, defined as the proportion of patients with documented TUT referral or a medication prescription in the EHR. Generalized estimating equations were used to estimate the parameters of a linear model.
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PMC10552951
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RESULTS
|
From June 2021 to July 2022, we randomly assigned 246 clinicians in 95 clusters, and collected TUT penetration data from their encounters with 2,146 eligible patients who smoke receiving oncologic care. Intent-to-treat (ITT) analysis showed that the clinician nudge led to a significant increase in TUT penetration versus usual care (35.6%
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PMC10552951
|
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CONCLUSION
|
EHR nudges, informed by behavioral economics and aimed at oncology clinicians, appear to substantially increase TUT penetration. Adding patient nudges to the implementation strategy did not affect TUT penetration rates.
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PMC10552951
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INTRODUCTION
|
cancer
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CANCER
|
Continued tobacco smoking by patients with cancer worsens quality of life (QoL) and reduces survival.
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PMC10552951
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CONTEXT
|
cancer, non-White
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CANCER
|
Are nudges informed by behavioral economics during oncology encounters with patients with cancer effective for increasing engagement in tobacco use treatment (TUT)?
Clinician nudges aimed at counteracting omission bias and delivered via the electronic health record resulted in a significant (>3-fold) increase in TUT engagement. The addition of a patient nudge did not affect TUTS engagement rates. Among clinicians, advanced practice providers were more likely than physicians to engage in TUT. White and non-White patients were equally engaged in TUT by the clinician nudge.
Clinician-focused nudges can provide important and timely cues to action that result in more patients engaging in TUT. Such nudges may be a low-cost, low-risk way to optimize use of tobacco cessation services during clinical encounters.**Relevance section written by Despite the importance of TUT, only half of the cancer centers consistently identify patient tobacco use,Implementation efforts to promote TUT engagement within oncology may be enhanced using behavioral economics, which has helped improve patient outcomes and transform health care delivery across a wide range of activities.We designed this pragmatic trial to test the effectiveness of patient- and clinician-directed implementation strategies, or nudges, informed by behavioral economics and delivered through the EHR, to counteract heuristics that reduce the likelihood of engaging in TUT. We compared the effects of nudges directed at patients, clinicians, or both to usual care on rates of TUT. We also performed a preliminary examination of patient and clinician characteristics that may moderate the impact of nudges on rates of TUT, including characteristics that may have important implications for health and social inequities, such as patient age, sex, race/ethnicity, and neighborhood-level SES.
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PMC10552951
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METHODS
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PMC10552951
|
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Design and Setting
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Cancer
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CANCER
|
We conducted a cluster-randomized pragmatic trial across five hospitals and six clinics within Penn Medicine's Abramson Cancer Center.
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PMC10552951
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Participant Eligibility
|
Diseases-10 cancer
|
RECRUITMENT
|
The clinician sample included physicians and advanced practice providers (APPs) within medical, radiation, and gynecologic oncology clinics. Eligibility criteria for clinicians included (1) currently practicing at an included site; (2) prescribing authority in Pennsylvania or New Jersey; (3) cared for ≥1 patient who used tobacco within the 30-day period preceding recruitment; and (4) English-speaking. Eligibility criteria for patients included any International Classification of Diseases-10 cancer diagnosis, self-reported current tobacco use assessed by staff initiating the visit, a scheduled appointment with a participating clinician, and English-speaking. Patients were accrued as they were seen by an eligible clinician.
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PMC10552951
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Study Procedures
|
Clinician enrollment proceeded in two steps: (1) announcement of study initiation at staff meetings, with opportunity to ask questions about design and impact on workflow, and (2) a personalized email delivered to all eligible clinicians reiterating study methods and providing instructions for opting out. All eligible clinicians (N = 246) were enrolled, with none opting out when offered. Patient enrollment began with a positive tobacco use assessment at the first patient visit within the study period, termed the
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PMC10552951
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Intervention Content
|
PMC10552951
|
|||
Clinician Nudge
|
The findings from our preliminary work examining physician preferences toward TUT revealed a strong preference for interventions perceived as effective.
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PMC10552951
|
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Patient Nudge
|
Status quo bias, or sticking with a current choice even if better alternatives exist, can reduce patient willingness to engage in TUT.
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PMC10552951
|
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Usual Care
|
Clinicians can refer to TUTS or offer TUT on their own without prompting. Our previous evidence suggests this rarely, if ever, happens.
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PMC10552951
|
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Measures
|
During preparation for this trial, we identified alternate workflows that clinicians used to provide tobacco use medications without referring patients to the TUT program.
|
PMC10552951
|
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Random Assignment
|
We randomized by clinician clusters identified on the basis of paired connections between physicians and APPs within networks of practice colleagues. Clusters were formed between clinicians with overlapping patient pools to reduce cross-cluster contamination. The clusters were not site-specific as many clinicians worked at multiple sites. We formed 95 clusters from 246 clinicians. Patients were nested under clinician clusters and assigned to an arm based upon the clinician they saw at their index visit, preventing crossover.
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PMC10552951
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Statistical Analysis
|
REGRESSION, SECONDARY
|
A sample of 900 patients provided ≥80% power to detect an 11% improvement in our primary outcome (eg, from 34% referral rate for current estimates to a clinically relevant 45%), using a two-sided type 1 error rate of 5% and an interclass correlation of 0.07, for planned comparisons between usual care and each nudge arm. We analyzed our binary outcome using logistic regression with generalized estimating equations (GEE). The study design is factorial, and models contained binary predictor terms for clinician and/or patient nudges. We included covariates from patients (eg, race) and clinicians (eg, clinician type) and controlled for time between visits in days. We controlled for type 1 error inflation by hierarchical testing, starting with the overall model significance, followed by effects of each nudge. Once we fitted the main effects model, we tested for interaction between nudges and retained the interaction term if significant. We followed the primary modeling with post hoc assessments of predictors, including our a priori interest in race, to assess interactions with study arm. Our primary analysis was intent-to-treat (ITT) so that all patients who completed the subsequent visit were included regardless of whether all interventions were received (N = 2,146). In a secondary analysis, we examined a GEE model that included only encounters wherein all nudges were received as intended (ie, a completer-only analysis; N = 1,795).
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PMC10552951
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RESULTS
|
PMC10552951
|
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Sample Characteristics and Covariates
|
Figure CONSORT diagram. For the assigned to usual care arm, treatment visit = 0 because of the nature of the intervention design. There are no nudges to be delivered. In other words, treatment is completed with the engaged visit, and there are no additional treatment visits. ITT, intent-to-treat.Baseline Demographics of Patients in Each Arm (ITT)Baseline Demographics of Clinicians in Each ArmFor patients who received the patient nudge, 55% opened the message, and, of those, 85% opened it on the day it was sent (average time to open = 1.39 days). Patients who did not receive the nudge were older (62.9
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PMC10552951
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Models of TUT
|
All models controlled for variables in Tables Generalized Estimating Equations Predicting TUT EngagementRates of tobacco treatment engagement across treatment arms (ITT model). ITT, intent-to-treat.Tobacco Treatment Engagement Rates by Study Arm, Model, and CovariatesIn both models, clinician type was associated with TUT penetration rates (Table Race was not associated with penetration of TUT in the models (Table
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PMC10552951
|
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DISCUSSION
|
cancer
|
CANCER
|
Nudges delivered through the EHR are a well-established way to affect clinical behaviors and can have a substantial effect on patient and implementation outcomes.The impact of patient-directed nudges is less well established, and depends on the style of the nudge and the nature of the target problem.When nudges are introduced to clinician workflows, they are particularly effective for increasing TUT penetration when APPs are handling clinical encounters. This may be due to training or perspective, with APPs engaging in this element of clinical care more readily than their physician counterparts. It is also likely that the details of cancer care workflow confound this association; physicians may be more likely to perform initial evaluations while APPs are more likely to perform follow-up care. If so, the over-representation of TUT among APPs may be a function of pragmatic care planning concerns.There are key strengths and limitations of this work. We used a pragmatic design and engaged both patients and clinicians—a key strength.Overall, this well-powered, rigorous pragmatic study demonstrates that implementation strategies, informed by behavioral economics within the EHR to counter biases that reduce health behavior engagement, can significantly increase the penetration of TUT in oncology care and do so without exacerbating health inequities in care delivery. Future work is needed to test the ability to generalize these findings to other health systems and to optimize the patient-directed nudge. Such work can continue to demonstrate the impact of implementation science and behavioral economics for enhancing the quality of cancer care to promote the best possible clinical outcomes for patients.
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PMC10552951
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PRIOR PRESENTATION
|
Presented in part at the AcademyHealth and NIH's 15th Annual Conference on the Science of Dissemination and Implementation in Health, Washington, DC, December 11-14, 2022.
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PMC10552951
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SUPPORT
|
Cancer
|
CANCER
|
Supported by a grant from the National Cancer Institute (P50 CA244690).
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PMC10552951
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CLINICAL TRIAL INFORMATION
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PMC10552951
|
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DATA SHARING STATEMENT
|
Participant data reported in the article, after deidentification, will be available at the time of publication, along with a data dictionary. A methodologically rigorous proposal to use the data should be provided to the corresponding author, Brian Jenssen (
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PMC10552951
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AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
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PMC10552951
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REFERENCES
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PMC10552951
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Background:
|
cirrhosis, HCC
|
CIRRHOSIS
|
Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive.
|
PMC10727671
|
Methods:
|
cirrhosis, fibrosis
|
CIRRHOSIS, FIBROSIS
|
This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months.
|
PMC10727671
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Results:
|
Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5–35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9–61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5–60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5–37.3;
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PMC10727671
|
||
Conclusions:
|
HCC
|
There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.
|
PMC10727671
|
|
INTRODUCTION
|
death, HCC
|
HEPATOCELLULAR CARCINOMA, LIVER CIRRHOSIS
|
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the United States, and the vast majority of cases occur in the setting of liver cirrhosis.Behavioral economics is a relatively new discipline that explores how humans have systematic biases that limit participation in prevention, such as inertia (status-quo bias) or overweighing current costs compared to future benefits (present-time bias).In this pragmatic trial, we evaluated the effect of opt-out framing with preordering with or without an unconditional $20 incentive on the response to HCC surveillance outreach among patients who are due for screening across a specialty practice.
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PMC10727671
|
METHODS
|
PMC10727671
|
|||
Study design
|
fibrosis, liver cirrhosis
|
FIBROSIS, LIVER CIRRHOSIS
|
This was a 3-arm randomized controlled trial applying behavioral economic approaches to encourage patients with liver cirrhosis or advanced fibrosis to complete routine surveillance ultrasounds. Eligible patients were randomized in a 1:2:2 ratio into 3 arms: (1) Usual care, (2) Letter + Order, or (3) Letter + Order + Incentive. They were identified in a series of 3 batches each 3 months apart, and randomization was stratified by batch. Patients in the Usual care arm received standard of care and were not mailed any outreach as part of this study. Patients in the Letter + Order arm were sent a letter invoking opt-out framing with an order slip for the ultrasound. Patients in the Letter + Order + Incentive arm were also sent a letter and order slip in addition to a $20 unconditional incentive.All research was conducted in accordance with both the Declarations of Helsinki and Istanbul. The study was approved by the Institutional Review Board at the University of Pennsylvania. A waiver of informed consent was obtained because the study was minimal risk to patients and could not have been practicably carried out without the waiver.
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PMC10727671
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Study population
|
liver cancer, cirrhosis, fibrosis, HCC
|
LIVER CANCER, CIRRHOSIS, FIBROSIS, METASTATIC CANCER, DISEASE
|
From our electronic health record (EHR), we identified all patients who were 18 years or older with a current diagnosis of cirrhosis or advanced fibrosis (as defined by the clinician in the EHR), were followed by gastroenterology or hepatology (with one or more visit to any gastroenterology or hepatology practice in the preceding 2 years) and who lived in the Philadelphia Metropolitan Statistical Area. For initial automated extraction, we used International Classification of Disease (ICD-10) codes (K74.60, K74.69, K70.31, K70.30) or cirrhosis in the active problem list of the EHR or in encounter diagnoses in the previous 3 years. Patients were excluded if they had completed liver cancer surveillance within the past 7 months, had a surveillance imaging test scheduled, or a different imaging modality (MRI or CT) recommended by their physician. Patients were also excluded if they had a history of HCC or other liver cancer diagnosis, history of liver transplant, metastatic cancer, or were receiving hospice care. Similarly, ICD-10 codes and the problem list were used for automated data extraction, complemented by manual chart review.Once patients were confirmed as eligible through a manual medical record review, the gastroenterology/hepatology providers were sent a message with a list of their eligible patients through the EHR and given the opportunity to opt their patients out of participation. If a provider chose to opt-out a patient, the patient was excluded from randomization.
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PMC10727671
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Interventions
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cirrhosis, HCC, fibrosis
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CIRRHOSIS, FIBROSIS
|
Eligible patients were identified and randomized through a series of 3 batches each approximately 3 months apart in September 2020, January 2021, and April 2021. Patients who were eligible and were not opted out of the intervention by their provider were randomized in a 1:2:2 allocation ratio using a computer-generated randomization algorithm stratified by batch. Patients in the Usual care arm received standard of care and were not mailed any study-related outreach. Patients randomized to the Letter + Order arm received a mailed letter describing the importance of HCC surveillance for patients with cirrhosis or advanced fibrosis and with messaging that encouraged them to get a surveillance ultrasound using the included order slip that had already been placed for them (opt-out framing). Patients in the Letter + Order + Incentive arm received the same letter and order slip in addition to a $20 unconditional incentive in the form of a gift card (ClinCard). Abdominal ultrasound orders were placed by a physician member of the research team (Shivani Kastuar), and the patient’s gastroenterology/hepatology provider was listed as the authorizing provider who would receive the results. The orders were then printed by the study team and matched to the personalized letters for mailing. All completed ultrasound results were routed to the patient’s gastroenterologist/hepatologist for follow-up, as per routine practice. At the time of this trial, there were no concurrent and systematic efforts to remind patients who were overdue for HCC surveillance.Patients who did not complete an abdominal ultrasound or other type of imaging within 2 months from the date of the initial outreach received a reminder letter with similar messaging to the original letter and including the ultrasound order slip. A reminder was not sent if the patient had a future ultrasound scheduled or if a different imaging modality (MRI or CT) was newly recommended by their provider. The investigators were blinded to patient data and randomization, but the research staff were not blinded as they were administering the interventions.
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PMC10727671
|
Study outcomes
|
cirrhosis, HCC, gastrointestinal clinic
|
SECONDARY, CIRRHOSIS
|
The primary outcome was the proportion of patients who completed an abdominal ultrasound within 6 months of initial outreach. The secondary outcome was the proportion of patients who had any HCC imaging within 6 months of initial outreach, including MRI or CT with contrast. Additional outcomes included evaluating differences in the completion rate by age, sex, race/ethnicity, income at the level of zip code, etiology of cirrhosis, provider and specialty, number of gastrointestinal clinic visits, patient portal status (active vs. inactive), and scheduling modality (self-schedule by means of patient portal vs. phone call). Additionally, we evaluated the percentage of imaging exams that were abnormal, resulted in follow-up imaging, resulted in a diagnosis of HCC and follow-up care, and incidental findings during imaging. Data were obtained from the EHR through automated data extraction and chart review for verification.
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PMC10727671
|
Statistical analysis
|
cirrhosis
|
REGRESSION, CIRRHOSIS
|
We estimated a 10% base response rate for the usual care arm based on prior studies and outreach programs. Based on a preliminary data review, we estimated that we would be able to identify approximately 600 eligible patients across the 3 batches. This sample size would provide 80% power to detect a 13 percentage point increase in response rate for the Letter + Order arm compared to the Usual Care arm (estimated 23%) and a 13 percentage point increase for the Letter + Order + Incentive arm compared to the Letter + Order arm (estimated 36%) using a two-tailed chi-squared test of proportions and a type 1 error rate of 0.025, accounting for 2 pairwise comparisons with Bonferroni correction (0.05/2).The chi-squared test of proportions was used to calculate the differences, 95% CIs, and We performed prespecified exploratory subgroup analyses for the primary outcome by age, sex, race/ethnicity, income, etiology of cirrhosis, provider and specialty, prior gastrointestinal clinic visits, and patient portal status. ORs for the treatment effects within subgroups were calculated using a multivariable logistic regression model with interaction terms. The treatment-by-subgroup interaction terms were analyzed one at a time in separate multivariable models. For the purposes of these analyses, age and income were represented as categorical variables. All analyses were performed using Stata version 15.0 (Stata Corp LP, College Station, Texas).
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PMC10727671
|
Qualitative analysis
|
HCC
|
A random subsample of 135 patients from the 2 intervention arms were called to complete a postintervention phone interview at least 6 months after initial outreach was mailed. A group of patients were randomly selected from each of the three batches proportionate to the batch size. The patients were asked about their experience with and perception of the impact of HCC surveillance outreach. We conducted a thematic analysis of the postintervention patient interviews to explore patient experience with the intervention and screening process.
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PMC10727671
|
|
RESULTS
|
PMC10727671
|
|||
Participants
|
comorbidity, cirrhosis, fibrosis
|
HEMOCHROMATOSIS, CIRRHOSIS, FIBROSIS, PRIMARY BILIARY CIRRHOSIS, PRIMARY SCLEROSING CHOLANGITIS, BUDD-CHIARI SYNDROME
|
A total of 615 patients were randomized; 53 patients were excluded from analysis postrandomization due to ineligibility (32 were up-to-date on screening, 12 had a future ultrasound scheduled, 5 were on hospice or had a severe comorbidity, 1 did not have a definitive diagnosis of cirrhosis or advanced fibrosis, and 3 had not had at least one visit in the prior 2 years). The proportion of patients excluded postrandomization was evenly distributed across the study arms (Supplemental Table S1, CONSORT flow diagram.Demographic characteristicsValues do not add up to total because some patients had more than one etiology of cirrhosis.Other includes other, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, and Budd-Chiari syndrome.American Community Survey (2014–2018) Median Household Income in 2018 inflated dollars.Number of gastroenterology clinic visits during the study window.Abbreviations: IQR, interquartile range; GI, gastrointestinal.
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PMC10727671
|
Ultrasound completion
|
Six months after the initial outreach, 27.6% (95% CI: 19.5–35.7) completed an abdominal ultrasound in the Usual care arm, 54.5% (95% CI: 47.9–61.0) completed an abdominal ultrasound in the Letter + Order arm, and 54.1% (95% CI: 47.5–60.6) completed an abdominal ultrasound in the Letter + Order + Incentive arm. There was a significant increase in the ultrasound response rate in the Letter + Order arm compared to the Usual care arm (absolute difference of 26.9%; 95% CI: 16.5–37.3; Proportion of patients completing abdominal ultrasound in the 6-month period
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PMC10727671
|
||
Any imaging completion
|
At 6 months after the initial outreach, 59.4% (95% CI: 52.9–65.8) completed any imaging (US, MRI, or CT) in the Letter + Order arm, 57.2% (95% CI: 50.7–63.7) completed any imaging in the Letter + Order + Incentive arm, and 32.8% (95% CI: 24.2–41.3) completed any imaging in the Usual Care arm. There was a significant increase in the imaging response rate in the Letter + Order arm compared to the Usual care arm (absolute difference of 26.6%; 95% CI: 15.9–37.3; Proportion of patients completing any imaging (US, MRI, or CT) in the 6-month period
|
PMC10727671
|
||
Screening outcomes
|
HCC, BCLC
|
A total of 298 patients across arms completed any imaging (US, MRI, or CT) in the 6-month period following the initial outreach. Of those, 14 (4.7%) had abnormal results or required additional follow-up evaluation. Based on medical record review to date, 11 (78.6%) were ordered follow-up imaging, 9 (81.8%) completed follow-up imaging, and 4 (44.4%) were diagnosed with HCC (Table Patients with any abnormal liver imaging (US, MRI, or CT) and subsequent careBarcelona Clinic Liver Cancer (BCLC) stage at diagnosis: 1 stage A, 2 stage B, and 1 stage C.Among the 298 patients who completed imaging, 34 (11.4%) had incidental findings that were not liver related (Table
|
PMC10727671
|
|
Subgroup analyses
|
The subgroup analysis demonstrated a similar response to the interventions across demographic and clinical factors, with no significant interaction terms when accounting for multiple comparisons (Supplemental Figure S1,
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PMC10727671
|
||
Qualitative interviews
|
A total of 135 patients in the intervention arms (opt-out and incentive arms only) were randomly selected to be contacted for a postintervention interview (stratified by batch). Of these, 18 interviews (13.3%) were completed, 37 declined (27.4%), 69 were unreachable (51.1%), and 11 had other issues (8.1%). Of the 5 that specifically remembered the letter, 4 found it to be useful. Almost half of the patients (n=7) preferred to schedule the ultrasound by phone, while one third (n=6) preferred to schedule during the office visit. Five patients found the patient portal useful for engagement, and 4 patients had issues with receiving mail from the postal service due to reliability. Five patients had to put off liver surveillance due to the COVID-19 pandemic, 3 patients appreciated the gift card, and 3 had issues with transportation to receive the ultrasound.
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PMC10727671
|
||
DISCUSSION
|
cancers, colorectal cancer, HCC
|
CANCERS, HEPATITIS C, COLORECTAL CANCER, LIVER DISEASE
|
In this study, we found that mailed outreach with opt-out framing and a signed preorder doubles the participation in HCC surveillance. However, there was no additional effect due to the $20 unconditional financial incentive when added to the mailed outreach intervention. Importantly, we did not find differential effectiveness by sociodemographic characteristics in the subgroup analyses. In the exploratory analysis, we also found that more cancers were identified in the intervention group than in the control group.The effectiveness of the opt-out intervention may be explained by a few factors. First, it provided direct mail to remind patients about surveillance in a population health approach that does not rely on a visit to a specialist physician. Many patients may not be scheduled or may not attend a visit, which is the conventional opportunity for clinicians to remind patients about surveillance. The subgroup analysis showed that there may have been a greater effect among those without a visit during the trial period. This intervention provided an opportunity to participate during the COVID-19 pandemic, when patients may have missed routine visits. Additionally, the letter served as a nudge to remind patients if the ultrasound was ordered many months before but was forgotten. The letter also used preordering with opt-out framing, implying that participation in HCC surveillance is the default and the patient would have to actively choose not to participate. This has been shown to increase screening for colorectal cancer and hepatitis C in other trials.This study supports and adds to the literature on direct outreach for HCC surveillance. A trial at a safety net health system across all practices (not just specialty) evaluating mailed outreach with telephone follow-up showed a similar increase in one-time surveillance from 24.3% to 44.5%, with continued effectiveness over 18 months and a modest benefit from navigation.There are a few reasons why the financial incentive may not have increased response rate. First, the $20 incentive may not have been large enough to overcome any barriers for the patients to attend the ultrasound. Larger incentives of $100 have been shown to increase participation in screening colonoscopy among health system employees. The unconditional incentive may not have had as much effectiveness as other behaviorally informed incentives in this context, such as conditional or lottery-based incentives,The main strength of this study was the prospective randomization that controlled for unobserved variables and allowed for the evaluation of the effect of each specific intervention. It was conducted in a pragmatic design in partnership with routine clinical operations; therefore, the results can be generalized to other practices. We also evaluated a scalable approach to surveillance that can leverage EHR processes such as preordering and letter generation. A future state may be able to leverage a bulk ordering process that has been used in other preventive health exams. The study population had a high percentage of Black and Medicaid patients, groups who typically have known disparities and worse outcomes for liver disease.This study has some important limitations. While we showed the benefit of one-time surveillance, repeat surveillance over time is required to effectively reduce the burden of HCC, although prior studies have shown that this process can be repeated and sustained. This was conducted at an academic tertiary care center, so it may not translate to other care settings. Surveillance performed outside of the health system may have been missed. Although we conducted a chart review and allowed clinicians to opt-out of ineligible patients, we may have missed exams in the outcome ascertainment, and this could have biased toward higher effectiveness in the intervention arms. Additionally, this trial was conducted during the COVID-19 pandemic, although clinical visits and imaging appointments were available at that time.In summary, we found that sending mailed outreach with orders increased the response to HCC surveillance in a diverse population of patients followed by gastroenterology/hepatology specialists. This approach can be used by health systems to increase adherence to guidelines for population health management in patients with advanced liver disease. Additional research is needed to evaluate its long-term effectiveness in different populations.
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PMC10727671
|
Supplementary Material
|
PMC10727671
|
|||
SUPPLEMENTARY MATERIAL
|
PMC10727671
|
|||
FUNDING INFORMATION
|
Cancer
|
CANCER
|
This trial was funded as a UPenn P30 Roybal Center Pilot Project from the National Institute of Aging (5P30AG03456-10). Dr Shivan J. Mehta’s time was supported by grant number K08CA234326 from the National Cancer Institute. The funders had no role in the design, conduct, or analysis of the study.
|
PMC10727671
|
CONFLICTS OF INTEREST
|
Dr Shivan J. Mehta has received compensation from Guardant Health and the American Gastroenterological Association. Dr Tessa S. Cook is on the speakers’ bureau for Spectra. The remaining authors have no conflicts to report.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website,
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PMC10727671
|
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REFERENCES
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PMC10727671
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Abstract
|
Psoriasis, psoriasis
|
GENERALIZED PUSTULAR PSORIASIS, ERYTHRODERMIC PSORIASIS, PSORIASIS, PSORIASIS
|
Risankizumab, a humanized immunoglobin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, is approved in Japan to treat numerous indications, including generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). Both GPP and EP are severe forms of psoriasis that have limited treatment options. In IMMspire (A Study to Assess Efficacy and Safety of Two Different Dose Regimens of Risankizumab Administered Subcutaneously in Japanese Subjects With Generalized Pustular Psoriasis or Erythrodermic Psoriasis) (NCT03022045), a phase 3, randomized, multicenter study in Japan, we evaluated the efficacy and safety of risankizumab for Japanese adults with GPP or EP. Patients were randomized (1:1) to receive open‐label risankizumab 75 mg or 150 mg at weeks 0 and 4 and every 12 weeks thereafter through week 160. The primary efficacy end point was GPP or EP clinical response at week 16. Other efficacy end points included GPP or EP clinical response, ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index of 0 or 1 (DLQI 0/1) through 180 weeks (last follow‐up visit). Safety was assessed throughout. A total of 17 patients (eight with GPP and nine with EP) were enrolled. All patients achieved the primary end point of GPP or EP clinical response at week 16. Among patients continuing risankizumab treatment, achievement of GPP or EP clinical response, PASI 90 and DLQI 0/1 were generally sustained throughout the treatment. The safety profile remained consistent with the safety profiles noted in previous risankizumab studies. Risankizumab demonstrated clinically meaningful efficacy at week 16, with durable efficacy and a favorable long‐term safety profile in Japanese patients with GPP or EP.
|
PMC10107196
|
INTRODUCTION
|
multisystem disorder, psoriasis
|
ERYTHRODERMIC PSORIASIS, GENERALIZED PUSTULAR PSORIASIS, PSORIASIS, STERILE, PSORIATIC ARTHRITIS, PLAQUE PSORIASIS
|
Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are severe and rare forms of psoriasis. In patients with GPP, numerous tiny, sterile pustules cover the entire body and may cause a fatal multisystem disorder.Risankizumab, a humanized immunoglobin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, is approved in Japan to treat plaque psoriasis, GPP, EP, and psoriatic arthritis in adults.
|
PMC10107196
|
METHODS
|
PMC10107196
|
|||
Patients
|
erythema
|
ACTIVE TUBERCULOSIS, ACUTE INFECTIONS, ERYTHEMA, VIRAL HEPATITIS, INFLAMMATORY DISEASE
|
Eligible patients were aged 20 years or older and diagnosed with GPP or EP. Patients with GPP were diagnosed at least 60 days before informed consent was obtained, based on the Japanese Dermatological Association (JDA) criteria, and had an erythema area with pustules accounting for ≥10% of their body surface area and a JDA total severity score < 14. Patients with EP had inflammatory erythema accounting for ≥80% of their body surface area at screening. All patients with GPP or EP were candidates for systemic or phototherapy per the investigator's clinical judgment. Patients who had previous risankizumab exposure, medication‐induced or medication‐exacerbated EP, chronic or relevant acute infections (e.g., HIV, viral hepatitis, active tuberculosis), or other active ongoing inflammatory diseases that could potentially confound trial evaluations were excluded from the study.
|
PMC10107196
|
Study design and treatment
|
Psoriasis
|
PSORIASIS
|
IMMspire (A Study to Assess Efficacy and Safety of Two Different Dose Regimens of Risankizumab Administered Subcutaneously in Japanese Subjects With Generalized Pustular Psoriasis or Erythrodermic Psoriasis) (NCT03022045) was a phase 3, randomized, open‐label, parallel‐design study that compared two different doses of risankizumab in patients with GPP or EP. After screening, patients were randomized 1:1 to receive subcutaneous administration of open‐label risankizumab 150 mg or 75 mg at week 0 and week 4 and every 12 weeks thereafter through week 160. After marketing approval of risankizumab in Japan, the approved dosage and administration (risankizumab 150 mg at week 0 and week 4 and every 12 weeks thereafter [75 mg may be acceptable for some patients according to their condition]) was followed; no dose adjustments were made after approval. At week 16, patients who failed to achieve clinical response with risankizumab 75 mg were allowed to increase the dose to 150 mg. One follow‐up visit was conducted 20 weeks after the last administration of the study drug. This clinical study was conducted in accordance with the protocol, International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines, and applicable guidelines and regulations governing ethical principles originating in the Declaration of Helsinki. An independent ethics committee/institutional review board ensured the ethical, scientific, and medical appropriateness of the study before it was conducted and approved all relevant documentation.
|
PMC10107196
|
Assessments
|
PMC10107196
|
|||
Efficacy
|
Psoriasis
|
PSORIASIS
|
The primary end point was the proportion of patients achieving clinical response at week 16. Clinical response was defined as “slightly improved” in the overall improvement rating from baseline according to the JDA total score for patients with GPP and as at least “minimally improved” in the Clinical Global Impression‐Global Improvement Scale for patients with EP. Secondary end points included the proportion of patients achieving clinical response at week 52 and ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52. Other efficacy end points assessed through week 180 (the last follow‐up visit) included achievement of clinical responses, PASI 90, Dermatology Life Quality Index of 0 or 1 (no effect) (DLQI 0/1), and change from baseline in total JDA scores (0 [best] to 17 [worst]) for patients with GPP.
|
PMC10107196
|
Safety
|
Laboratory abnormalities, Cancer
|
ADVERSE EVENTS, ADVERSE EVENT, CANCER
|
Evaluation of safety included monitoring of adverse events (AEs), serious AEs (SAEs), changes in vital signs and clinical laboratory tests, and local tolerability. Laboratory abnormalities were classified by the National Cancer Institute Common Terminology Criteria for Adverse Events.
|
PMC10107196
|
Statistical analysis
|
The sample size was not powered for any hypothesis testing because of the limited number of enrolled patients; thus, the sample size was determined based on feasibility. All efficacy and safety analyses were conducted for the intent‐to‐treat population (all randomized patients who received one or more dose of the study drug). No patients were excluded from the analyses. In addition to the as‐observed analysis, nonresponder imputation and last‐observation‐carried‐forward analyses were used to handle missing data for binary and continuous end points, respectively.
|
PMC10107196
|
||
RESULTS
|
PMC10107196
|
|||
Patients
|
Pustular Psoriasis, PGA‐GPP, Psoriasis, tumor necrosis
|
ERYTHRODERMIC PSORIASIS, TUMOR NECROSIS, PSORIASIS, DISEASE, GENERALIZED PUSTULAR PSORIASIS
|
A total of 17 patients, including eight patients with GPP and nine patients with EP, were enrolled and 10 (58.8%) patients completed the study Patient disposition. Baseline demographics and disease characteristicsAbbreviations: BMI, body mass index; BSA, body surface area; DLQI 0/1, Dermatology Life Quality Index of 0 or 1 (no effect); EP, erythrodermic psoriasis; JDA, Japanese Dermatological Association; NA, not applicable; PASI, Psoriasis Area and Severity Index; PGA‐GPP, Physician's Global Assessment of Generalized Pustular Psoriasis; SD, standard deviation; TNFi, tumor necrosis factor α inhibitor.Only applicable to patients with generalized pustular psoriasis (GPP).
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PMC10107196
|
Efficacy
|
PMC10107196
|
|||
Patients with
|
Psoriasis
|
GENERALIZED PUSTULAR PSORIASIS, ERYTHRODERMIC PSORIASIS, PSORIASIS
|
All patients with GPP achieved the primary end point of clinical response at week 16 with risankizumab treatment, regardless of dose (Table Efficacy of risankizumab in Japanese patients with GPP or EPAbbreviations: CI, confidence interval; DLQI 0/1, Dermatology Life Quality Index of 0 or 1 (no effect); PASI 90; ≥90% reduction from baseline in Psoriasis Area and Severity Index.Three patients with generalized pustular psoriasis (GPP) discontinued after week 16, one discontinued after week 52, and one discontinued after week 124.Two patients with erythrodermic psoriasis (EP) discontinued after week 52.Clinical response is defined as the proportion of patients achieving GPP clinical response (“slightly improved” in the overall improvement rating from baseline according to the Japanese Dermatological Association [JDA] total score) for patients with GPP or the proportion of patients achieving EP clinical response (“minimally improved” in the Clinical Global Impression‐Global Improvement scale) for patients with EP.Japanese Dermatological Association (JDA) total score over time in patients with generalized pustular psoriasis (GPP). (a) Mean change from baseline by visit. (b) JDA total score for individual patients; each colored line represents one patient.
|
PMC10107196
|
Patients with
|
Similarly, all patients with EP achieved the primary end point of clinical response with risankizumab treatment, regardless of dose (Table
|
PMC10107196
|
||
Safety
|
hypoadrenalism, death, deterioration of hepatic function, ischemic heart failure, kidney calculus, pain, rash, Alcoholic liver disorder, scirrhous gastric cancer
|
DISORDER, HYPOADRENALISM, ERYTHRODERMIC PSORIASIS, ADVERSE EVENTS, INFLAMMATION, URINARY CALCULUS, ADVERSE EVENT, GENERALIZED PUSTULAR PSORIASIS, ALCOHOLIC LIVER DISORDER, URINARY TRACT INFECTION
|
Treatment‐emergent AEs were reported for most (88.2%) patients (Table Safety overview of risankizumab in Japanese patients with GPP or EPAbbreviations: AE, adverse event; EP, erythrodermic psoriasis; GPP, generalized pustular psoriasis; TEAE, treatment‐emergent adverse event.As assessed by the study investigator.Patient with scirrhous gastric cancer on day 113 that led to study drug discontinuation; considered not related to study drug.Alcoholic liver disorder on day 183; considered not related to study drug (related to heavy use of alcohol) and did not interrupt study drug.Patient had two serious adverse events (AEs; urinary tract infection [day 296] and hypoadrenalism [day 307]); both were considered not related to study drug, did not interrupt study drug, and resolved within 11 and 5 days, respectively.Urinary calculus on day 384; considered not related to study drug (related to preexisting kidney calculus) and resolved by day 433.Nonserious AE of inflammation, pain in extremity, and rash on day 1; considered not related to study drug.Serious AE of ischemic heart failure leading to death on day 675; considered not related to study drug.Nonserious elevation in liver enzymes; resolved 64 days later and did not lead to study drug disruption.Nonserious aggravation of hepatic function disorder on day 85; considered not related to study drug and did not lead to study drug interruption; concomitant medications were discontinued.Nonserious deterioration of hepatic function on day 86; considered not related to study drug and did not lead to study drug interruption.Nonserious elevation in total bilirubin; resolved 176 days later and did not lead to study drug interruption.
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PMC10107196
|
DISCUSSION
|
psoriasis
|
PSORIASIS
|
Results from IMMspire demonstrated clinically meaningful efficacy with risankizumab, regardless of dose (75 or 150 mg); all patients achieved the primary end points of clinical response at week 16. Most patients achieved skin clearance assessed by PASI 90 at week 16. In addition, most of the patients who received risankizumab achieved DLQI 0/1 (no effect on patient's life) at week 16, which may suggest that risankizumab may help improve patient's quality of life. Overall, long‐term treatment with risankizumab demonstrated durable high rates of skin clearance in patients with GPP or EP. All patients who continued with risankizumab therapy maintained a clinical response at week 160.Risankizumab was generally well tolerated by patients with GPP or EP, and no new safety signals were identified. The safety profile of risankizumab observed through 160 weeks of therapy and follow‐up through 180 weeks was consistent with the safety profile of risankizumab observed through 172 weeks of treatment in patients with psoriasis.IMMspire has some limitations. First, the interpretation of efficacy and safety outcomes is limited by the lack of a placebo group. Second, the open‐label nature of the study may introduce bias as patients and investigators were aware of the study treatment. Last, the small sample size of the study may overestimate the magnitude of efficacy and AEs. Despite these limitations, findings from the present study suggest that there are positive treatment benefits for Japanese patients with GPP and EP.In conclusion, the results from IMMspire showed clinically meaningful and durable efficacy of risankizumab over time in patients with GPP or EP. Efficacy was achieved at week 16 and maintained throughout treatment, and up to the last follow‐up visit. The safety profile was consistent with the safety profiles outlined in other psoriasis studies with risankizumab treatment. These results suggest that risankizumab may be an effective long‐term treatment option for GPP or EP.
|
PMC10107196
|
CONFLICT OF INTEREST
|
SKIN
|
AbbVie participated in the study design; study research; collection, analysis, and interpretation of data; and writing, reviewing, and approving this manuscript for publication. All authors had access to the data, participated in the development and review of the document, and agreed in the decision to submit this manuscript for publication. No honoraria or payments were made for authorship. K.Y. has served as a clinical trials investigator for AbbVie, Boehringer Ingelheim, Eli Lilly Japan, LEO Pharma, Janssen, Maruho, MSD, Parexel, and UCB Japan. He has received research funding from AbbVie, Eisai, Eli Lilly Japan, Kyowa Kirin, Maruho, Sasaki Chemical, Sun Pharma, Taiho Yakuhin, and Torii Yakuhin. In addition, he has received speaker's fees and chair's fees from AbbVie, Astellas Seiyaku, Celgene, Daiichi‐Sankyo, Eisai, Eli Lilly Japan, Janssen, Kyowa‐Hakko Kirin, LEO Pharma, Maruho, Nippon Kayaku, Nippon Zouki, Novartis, Sun Pharma, Sato Seiyaku, Sanofi, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin. Y.O. has received grants from Eisai, Maruho, Shiseido, and Torii; consulting/advisory board fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Janssen, and Sun Pharma; speakers' bureau fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Jimro, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho, Torii, and UCB; and fees for participating in clinical trials sponsored by AbbVie, Amgen, Boehringer Ingelheim, Bristol‐Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Maruho, Pfizer, Sun Pharma, and UCB. I.Y., N.S., and I.M. are employees of AbbVie Inc. or AbbVie GK, and may hold AbbVie stock and/or stock options. A.M. has received honoraria from AbbVie, Ayumi Pharmaceutical, Boehringer Ingelheim, Celgene, Eisai, Eli Lilly, Inforward, Janssen, Kyowa Kirin, Maruho, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Taiho, Torii, and Ushio. He has received research support from AbbVie, Eisai, Eli Lilly, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Novartis, Taiho Pharma, and Torii. He has also served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Kyowa Kirin, Maruho, Mitsubishi Tanabe, Nichi‐Iko Pharmaceutical, Nippon Kayaku, Novartis, NPO Health Institute Research of Skin, Pfizer, Sun Pharma, Torii, and UCB.
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PMC10107196
|
|
ACKNOWLEDGMENTS
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AbbVie and the authors thank all of the study investigators for their contributions and the patients who participated in this study. All authors had access to the data and participated in the development, review, critique, and approval of the manuscript throughout the editorial process, and approved the final manuscript draft submitted for publication. All authors agree to be accountable for all aspects of the work, ensuring the accuracy and integrity of the publication. All named authors meet the International Committee of Medical Journal Editors criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published. A.M. contributed to the study concept and design. K.M., Y.O., and A.M. contributed to data acquisition. I.Y. contributed to statistical analysis. I.Y., N.S., I.M., and A.M. contributed to data interpretation. AbbVie funded the research for this study and provided writing support for this manuscript. Medical writing support, funded by AbbVie, was provided by Melissa Julyanti, PharmD, of JB Ashtin. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized individual and trial‐level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement. Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link:
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PMC10107196
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REFERENCES
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PMC10107196
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Background
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Creatine is an organic compound that facilitates the recycling of energy-providing adenosine triphosphate (ATP) in muscle and brain tissue. It is a safe, well-studied supplement for strength training. Previous studies have shown that supplementation increases brain creatine levels, which might increase cognitive performance. The results of studies that have tested cognitive performance differ greatly, possibly due to different populations, supplementation regimens, and cognitive tasks. This is the largest study on the effect of creatine supplementation on cognitive performance to date.
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PMC10647179
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Methods
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Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each. We tested participants on Raven’s Advanced Progressive Matrices (RAPM) and on the Backward Digit Span (BDS). In addition, we included eight exploratory cognitive tests. About half of our 123 participants were vegetarians and half were omnivores.
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PMC10647179
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