ChemInform Research Articles

Smoking cessation assistance among pneumologists and thoracic surgeons in Switzerland: a national survey

ObjectiveSmoking, with a prevalence of about 25%–30% in Switzerland, is proven to cause major systemic, avoidable diseases including lung cancer, increasing societies morbidity and mortality. Diverse strong quitting smoking recommendations have been made available providing advice facilitating smoking cessation globally. In other European countries like Germany, clinical practice guidelines for smoking cessation services have been implemented. However, in Switzerland, there is still no national consensus on a comprehensive smoking cessation program for lung cancer patients nor on the adequate provider. Our primary aim was to assess the current status of smoking cessation practice among specialists, mainly involved in lung cancer care, in Switzerland in order to uncover potential shortcomings.Material and methodsA self-designed 14-items questionnaire, which was reviewed and approved by our working group consisting of pneumologists and thoracic surgeons, on demographics of the participants, the status of smoking cessation in Switzerland and specialists' opinion on smoking cessation was sent to thoracic surgeons and pneumologists between January 2024 and March 2024 via the commercially available platform www.surveymonkey.com. Data was collected and analysed with descriptive statistics.ResultsSurvey response rate was 22.25%. Smoking cessation was felt to positively affect long term survival and perioperative outcome in lung cancer surgery. While 33 (37.08%) physicians were offering smoking cessation themselves usually and always (35.96%), only 12 (13.48%) were always referring their patients for smoking cessation. Patient willingness was clearly identified as main factor for failure of cessation programs by 63 respondents (70.79%). Pneumologists were deemed to be the most adequate specialist to offer smoking cessation (49.44%) in a combination of specialist counselling combined with pharmaceutic support (80.90%).ConclusionThe development of Swiss national guidelines for smoking cessation and the implementation of cessation counselling in standardized lung cancer care pathways is warranted in Switzerland to improve long-term survival and perioperative outcome of lung cancer patients.

Can we apply the concept of sentinel lymph node in rectal cancer surgery?

Introduction Colorectal cancer remains one of the most common causes of cancer-related mortality worldwide, and lymph node staging is crucial in the diagnostic and therapeutic process. Sentinel lymph nodes are the first involved in this process, but their validity in colorectal surgery has not yet been established. Following the emergence of new imaging instrumentation, some authors have attempted to propose different techniques for lymph node identification. However, a clear pattern of mesorectal lymph node distribution relative to the primary lesion site has yet to be defined. Material and methods Our analysis retrospectively reviewed suspicious mesorectal pathological lymph nodes on pre-operative magnetic resonance imaging (MRI) of rectal cancer patients, in order to assess the distribution patterns of possible tumour-related rectal lymph nodes. Mesorectal space was subdivided into quadrants and levels, and morphological features and distances from the lymph node to the primary rectal tumour were recorded. Results Two hundred and fifty-five mesorectal lymph nodes distributed among 60 patients were collected. Results show that in 92.1% of cases, nodes were distributed in the same mesorectal quadrant as the rectal primary tumour, and in 88.5% of cases, they were found at the same level as the rectal primary tumour. Conclusions Although a clear node distribution pattern was not established, these results may suggest at least a lymphatic drainage preference lane, worthy of further investigation.

Engineering of a hydroxysteroid dehydrogenase with simultaneous enhancement in activity and thermostability for efficient biosynthesis of ursodeoxycholic acid.

Hydroxysteroid dehydrogenases have emerged as indispensable tools in the synthesis of steroids, bile acids, and other steroid derivatives for the pharmaceutical and chemical industries. In this study, a novel approach was developed to simultaneously improve the stability and activity of a hydroxysteroid dehydrogenase by combining B-factor analysis and computer-aided prediction. This semi-rational method was demonstrated to be highly effective for enzyme engineering. In addition, NAD kinase was introduced to convert NAD+ to NADP+ for effective coenzyme regeneration in the whole-cell multienzyme-catalyzed system. This strategy reduces the significant economic costs associated with externally supplemented cofactors in NADP-dependent biosynthetic pathways.

Supercharged Phosphotriesterase for improved Paraoxon activity.

Phosphotriesterases (PTEs) represent a class of enzymes capable of efficient neutralization of organophosphates (OPs), a dangerous class of neurotoxic chemicals. PTEs suffer from low catalytic activity, particularly at higher temperatures, due to low thermostability and low solubility. Supercharging, a protein engineering approach via selective mutation of surface residues to charged residues, has been successfully employed to generate proteins with increased solubility and thermostability by promoting charge-charge repulsion between proteins. We set out to overcome the challenges in improving PTE activity against OPs by employing a computational protein supercharging algorithm in Rosetta. Here, we discover two supercharged PTE variants, one negatively supercharged (with -14 net charge) and one positively supercharged (with +12 net charge) and characterize them for their thermostability and catalytic activity. We find that positively supercharged PTE possesses slight but significant losses in thermostability, which correlates to losses in catalytic efficiency at all temperatures, whereas negatively supercharged PTE possesses increased catalytic activity across 25°C - 55°C while offering similar thermostability characteristic to the parent PTE. The impact of supercharging on catalytic efficiency will inform the design of shelf-stable PTE and criteria for enzyme engineering.

Telelactation Within the Landscape of Breastfeeding Support: Experiences of Latina Parents.

Despite increasing breastfeeding initiation rates in the United States, disparities in breastfeeding continuation and exclusivity by race and ethnicity persist. We aimed to understand the perceptions and experiences of Latina parents who received access to telelactation, and assessed the implications of integrating telelactation into pediatric settings. This cross-sectional qualitative study drew from participants enrolled in a randomized controlled trial about breastfeeding support. We recruited 20 participants from among those participating in a randomized controlled trial assessing the effect of telelactation on breastfeeding outcomes. The study design was informed by an Equity-Centered Model and authentic entry. We conducted a thematic content analysis through an iterative approach, where we systematically generated themes to describe code application patterns. We identified three themes: (1) telelactation within the broader landscape of breastfeeding support; (2) perceptions of telelactation support; and (3) recommendations on the use of telelactation in the context of pediatric care. We found that participants had an escalation approach for seeking breastfeeding support and propose a new model: Breastfeeding Support Escalation Protocol, which can be applied to lactation support in pediatric care. Parents' perceptions and recommendations highlighted their desire for care coordination, expanded options for telelactation engagement, and care continuity, which are important reflections for pediatric offices considering integrating telelactation services into their practice. Latina parents found telehealth to be helpful and an acceptable alternative to in-person services. Pediatric offices can take steps toward becoming Breastfeeding-Friendly by partnering with telelactation services. More research is needed on the logistical implications and cost-effectiveness of telelactation services as part of the pediatric practice.

Electronic Health Record Nudges and Health Care Quality and Outcomes in Primary Care

Nudges have been increasingly studied as a tool for facilitating behavior change and may represent a novel way to modify the electronic health record (EHR) to encourage evidence-based care. To evaluate the association between EHR nudges and health care outcomes in primary care settings and describe implementation facilitators and barriers. On June 9, 2023, an electronic search was performed in PubMed, Embase, PsycINFO, CINAHL, and Web of Science for all articles about clinician-facing EHR nudges. After reviewing titles, abstracts, and full texts, the present review was restricted to articles that used a randomized clinical trial (RCT) design, focused on primary care settings, and evaluated the association between EHR nudges and health care quality and patient outcome measures. Two reviewers abstracted the following elements: country, targeted clinician types, medical conditions studied, length of evaluation period, study design, sample size, intervention conditions, nudge mechanisms, implementation facilitators and barriers encountered, and major findings. The findings were qualitatively reported by type of health care quality and patient outcome and type of primary care condition targeted. The Risk of Bias 2.0 tool was adapted to evaluate the studies based on RCT design (cluster, parallel, crossover). Studies were scored from 0 to 5 points, with higher scores indicating lower risk of bias. Fifty-four studies met the inclusion criteria. Overall, most studies (79.6%) were assessed to have a moderate risk of bias. Most or all descriptive (eg, documentation patterns) (30 of 38) or patient-centeredness measures (4 of 4) had positive associations with EHR nudges. As for other measures of health care quality and patient outcomes, few had positive associations between EHR nudges and patient safety (4 of 12), effectiveness (19 of 48), efficiency (0 of 4), patient-reported outcomes (0 of 3), patient adherence (1 of 2), or clinical outcome measures (1 of 7). This systematic review found low- and moderate-quality evidence that suggested that EHR nudges were associated with improved descriptive measures (eg, documentation patterns). Meanwhile, it was unclear whether EHR nudges were associated with improvements in other areas of health care quality, such as effectiveness and patient safety outcomes. Future research is needed using longer evaluation periods, a broader range of primary care conditions, and in deimplementation contexts.

Current status of lung cancer care in Germany in the context of treatment centralization and lack of personnel

Lung cancer is the malignancy with the highest mortality rate worldwide. In January 2025, the German public healthcare system will introduce a new regulation according to which a centre can offer surgery for lung cancer only if it carries out a minimum number of lung resections. The purpose of this directive is to reduce the number of centres offering surgical treatment for primary lung cancer, thus centralising and improving lung cancer care. It is expected that the introduction of this regulation will lead to a significant shift in the staffing of thoracic units. The purpose of this survey was to examine the current occupational structures behind the units of thoracic surgery and respiratory medicine. We performed an online survey through the German Society for Thoracic Surgery and the Association of Respiratory Physicians. The responding centres were divided in two groups, centres that were certified by the German Cancer Society or the Society for Thoracic Surgery and centres which were not certified. The response rate was 29.3% (respiratory physicians) and 31.9% (thoracic surgeons); 67% of the participating colleagues answered that their unit was an independent department. The majority of the participants reported having to share the on-call duty of the trainees with other departments in order to be able to cover the required shifts. 35% of the respiratory physicians and 57% of the thoracic surgeons reported having vacant job posts in their units. The introduction of the minimum quantity regulation will have significant consequences for the treatment of lung cancer in Germany. The current staff shortage in healthcare will lead to both medical and nursing staff needing to be redistributed in order to meet the needs that will arise in 2025. Operating lists, theatre days, and operative equipment will need to be redistributed as well, not only within hospitals but probably on a nationwide level. A negative impact of the new regulation is to be expected on research and academic activities since most university hospitals are not expected to reach the minimum number of lung resections that is required in order keep performing lung cancer surgery.

Importance of Initial Ambulation as a Factor Influencing Length of Hospital Stay after Surgery for Colorectal Cancer

Importance of Initial Ambulation as a Factor Influencing Length of Hospital Stay after Surgery for Colorectal Cancer

Twenty-Five Years of Pediatric Critical Care Medicine: An Evolving Journey With the World Federation of Pediatric Intensive and Critical Care Societies.

Twenty-Five Years of Pediatric Critical Care Medicine: An Evolving Journey With the World Federation of Pediatric Intensive and Critical Care Societies.

Burnout Among Nurses Working in Critical Care Units in Africa: An Integrative Review

Background: Burnout is a syndrome resulting from chronic workplace stress that has not been effectively managed. The level of burnout that is experienced by nurses varies according to geographical region and specialties, such as paediatric and critical care nursing. However, little is known about burnout among nurses in African critical care units. Aim: To explore the available evidence on burnout among nurses in African critical care units. Methods: The review was guided by the Whittemore and Knafl framework for integrative review. Literature was searched in Web of Science, Embase, PubMed, and SCOPUS databases. The search strategy applied Boolean operators AND, OR using the following key terms: critical care nurses, burnout, and Africa. The alternative keywords were: nurs*, OR intensive care nurses OR Critical Care Nursing OR Intensive Care Nursing OR critical care nurs* AND “burnout syndrom*depersonalis/zation” OR “emotional exhaustion, workplace stress, Occupational Stresses, Professional Stress, Job-related Stress” AND specific names of the African countries. Findings: The review included eighteen articles. Two hundred and forty-nine nurses (n = 2,249) who work in critical care settings participated in the studies. The findings showed that nurses in critical care settings experience moderate to high levels of burnout, with emotional exhaustion being a common characteristic. Burnout is associated with factors related to the individual, work, and organization. The consequences of burnout include secondary traumatic stress, intention to leave the job, and increased risk of infection to the patient. Conclusions: The review has significant implications for nursing at various levels. The findings provided could inform future research and interventions to reduce burnout among critical care nurses in Africa.

An Opportunity for Synergizing Desalination by Membrane Distillation Assisted Reverse-Electrodialysis for Water/Energy Recovery.

Industry, agriculture, and a growing population all have a major impact on the scarcity of clean-water. Desalinating or purifying contaminated water for human use is crucial. The combination of thermal membrane systems can outperform conventional desalination with the help of synergistic management of the water-energy nexus. High energy requirement for desalination is a key challenge for desalination cost and its commercial feasibility. The solution to these problems requires the intermarriage of multidisciplinary approaches such as electrochemistry, chemical, environmental, polymer, and materials science and engineering. The most feasible method for producing high-quality freshwater with a reduced carbon footprint is demanding incorporation of industrial low-grade heat with membrane distillation (MD). More precisely, by using a reverse electrodialysis (RED) setup that is integrated with MD, salinity gradient energy (SGE) may be extracted from highly salinized MD retentate. Integrating MD-RED can significantly increase energy productivity without raising costs. This review provides a comprehensive summary of the prospects, unresolved issues, and developments in this cutting-edge field. In addition, we summarize the distinct physicochemical characteristics of the membranes employed in MD and RED, together with the approaches for integrating them to facilitate effective water recovery and energy conversion from salt gradients and freshwater.

Successful treatment of anastomotic leakage with an intestinal obstruction catheter and stent by colonoscopy: a case report and brief literature review

BackgroundAnastomotic leakage (AL) is one of the most common, severe, and difficult-to-treat complications after colorectal cancer surgery. However, to date, the best treatment options for AL remain elusive.Case descriptionHere, we report the case of a 70-year-old man who had previously undergone Hartmann’s surgery and developed a large AL after a colostomy reversal surgery in an external hospital. The condition mainly manifested as passage of the fecal material through the abdominal drainage tube accompanied by fever after intestinal surgery. We used a new method involving a transanal obstruction catheter combined with an anastomotic stent, along with fasting, administration of parenteral nutrition, and anti-infection treatment. By following this approach, AL was successfully cured without any complications.ConclusionTo the best of our knowledge, this is the first case of the use of a transanal intestinal obstruction catheter combined with an anastomotic stent for treating colorectal AL; the findings may guide clinicians to better treat and manage AL.

Dysphagia is a strong predictor of revision supraglottoplasty in pediatric laryngomalacia

BackgroundThere is growing research on the association between swallowing dysfunction and laryngomalacia. Supraglottoplasty is the surgical intervention used to treat laryngomalacia, however a portion of patients who undergo this procedure will require a revision surgery. Predictive risk factors for revision supraglottoplasty in patients with laryngomalacia are not well understood, and previous studies failed to evaluate swallowing systematically. HypothesisWe predict a significant association between swallowing dysfunction and revision supraglottoplasty for patients with laryngomalacia. MethodsThis was a retrospective cohort study of consecutive patients between 2013 and 2023 at a tertiary pediatric care centre (Stollery Children's Hospital). All patients had an endoscopic diagnosis of laryngomalacia by a staff otolaryngologist and at minimum a systematic clinical swallowing assessment by a speech language pathologist, with an instrumental assessment as needed. Patients with genetic or neurological comorbidities, lack of follow up information, or age of >3 years were excluded. Clinical and instrumental swallow data, demographic information, surgical outcomes and revision surgeries were documented and collected. Univariate analysis was done to determine associations between variables and revision supraglottoplasty. Binary logistic regression was done to determine independent predictors of revision supraglottoplasty. Results214 patients met the inclusion criteria and were analyzed in the study. 24 patients (11 %) required revision supraglottoplasty. 118 out of the 214 patients (55 %) had an instrumental assessment completed (FEES or VFSS). Of those, 92 (78 %) had abnormal findings on instrumental assessments. Univariate analysis showed Type 2 laryngomalacia (P = 0.017), presence of aspiration (P=<0.001), presence of cyanosis (P = 0.002) and abnormal findings on an instrumental assessment (P = 0.013) to be significantly associated with the need for revision supraglottoplasty. Binary regression analysis showed aspiration (OR = 5.6 {2.087–14.889}, P=<0.001) and cyanosis (OR = 5.3 {1.852–15.181}, P = 0.002) to be the only independent predictors of revision supraglottoplasty. ConclusionPresence of aspiration is a strong predictive factor for revision supraglottoplasty in patients with laryngomalacia, when swallowing is evaluated systematically. More prospective research is needed to understand the relationship between swallowing dysfunction, laryngomalacia and surgery.

EHealth in pediatric respiratory allergy.

This review explores the relevance of eHealth technologies to address unmet needs in pediatric respiratory allergies, particularly allergic rhinitis (AR) and asthma. Given the increasing burden of these conditions, there is a pressing need for effective solutions to enhance disease surveillance, diagnosis, and management. Recent literature highlights the potential of eHealth tools to transform pediatric respiratory allergy care. The use of digital data for infodemiology, application of machine learning models to improve diagnostic sensitivity, smartphone apps with digital patient reported outcome measure (PROMs) and embedded sensors to monitor disease, healthcare professional dashboards with real-time data monitoring and clinical decision support systems (CDSS) are advances emerging to optimize pediatric respiratory allergy care. Integrating eHealth technologies into the pediatric respiratory allergy care pathway is a potential solution for current healthcare challenges to better meet the needs of children with AR and asthma. However, while the potential of eHealth is evident, its widespread implementation in real-world practice requires continued research, collaboration, and efforts to overcome existing barriers.

Heart rate to identify non-febrile children with dehydration and acute kidney injury in emergency department: a prospective validation study.

This study prospectively validates the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. An EHRV > 24.5% could serve as a marker for suspecting dehydration or AKI. Further validation across diverse patient populations and settings is needed. • An increased heart rate (HR) is a readily detectable sign of dehydration in children. • In a retrospective validation cohort, an estimated HR variation (EHRV) greater than 24.5% compared to the 50th percentile of HR was predictive of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile patients. • We prospectively validated the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. • We confirmed that an EHRV greater than 24.5% is associated with increased odds of ≥ 5% dehydration and AKI.

ASO Author Reflections: Impact of Sarcopenia on Patient-Reported Outcomes After Video-Assisted Thoracoscopic Surgery for Lung Cancer.

ASO Author Reflections: Impact of Sarcopenia on Patient-Reported Outcomes After Video-Assisted Thoracoscopic Surgery for Lung Cancer.

Minimally Invasive Surgery: Is It a Risk Factor for Postoperative Peritoneal Metastasis in pT4 Colon Cancer?

Performing laparoscopic surgery for T4 colon cancer remains controversial because of concerns about whether its oncologic outcomes are comparable to those of open surgery, and postoperative peritoneal metastasis (PM) has been reported to occur more frequently in laparoscopic colectomy for T4 colon cancer. We investigated whether minimally invasive surgery (MIS) demonstrated a higher PM rate than open surgery and analyzed the risk factors for PM in pT4 colon cancer. This study included 392 patients with pT4 colon cancer who underwent curative surgery at a referral hospital between January 2000 and December 2018. Patients with previous neoadjuvant therapy, synchronous malignancy, metastasis, or those who underwent hyperthermic intraperitoneal chemotherapy were excluded. The MIS group had fewer high-risk clinical features, such as tumors too large for endoscope admission or complications like perforation and fistula. The group also exhibited shorter operative time, intraoperative blood loss, multivisceral resection, hospital stay, fewer postoperative complications, smaller tumor size, lower pT4b ratio, and higher pN+ rates. Multivariate analysis revealed that high-risk clinical features, MIS, pT4b, pN+, tumor size < 5 cm, high histological grade, lymphovascular invasion, and postoperative complications were significant risk factors for PM. During the median 59-month follow-up, the 5-year cumulative incidence of PM was elevated in the MIS group (17.5% vs. 8.2%; P = 0.057). No significant differences were observed in the 5-year overall and disease-free survival rates. Minimally invasive surgery increases the risk of postoperative PM in patients with pT4 colon cancer. Surgeons may require thorough tumor staging and radical resection to prevent PM.

Voices of Parent-Carers Navigating the Care for Children With Osteogenesis Imperfecta.

Parent-carers of children with rare diseases, including osteogenesis imperfecta (OI), represent a vulnerable and largely invisible population. Despite existing research on familial OI caregiving, the unique experiences, perspectives, and feelings of parent-carers remain poorly understood, prompting this study to delve into these aspects through the subjective lens of voices. The aim of this study was to explore the voices of parent-carers in navigating the complexities of pediatric OI care. Employing a narrative design informed by social constructionism, 15 parent-carers of pediatric OI patients were purposively sampled from a tertiary hospital in Shandong Province, China, between May and August 2021. Individual face-to-face interviews were conducted, and data were analyzed using the voice-centered relational approach followed by thematic analysis. Parent-carers' narratives revealed two overarching themes. The first theme, "the all-encompassing caregiver role," highlighted the profound internal transformation parent-carers underwent, with three key aspects of experiences: "the centrality of care," "life on hold," and "guarded silence." The second theme, "navigating ambivalence," captured the complex psycho-emotional journey of parent-carers as they balanced denial and acceptance, experienced the burden and responsibility of caregiving, navigated uncertainty with hope, and sought to normalize the care recipients' experiences while acknowledging their unique needs. Our findings suggest the need for developing tailored support strategies that address not only practical challenges but also the psychosocial dimensions of caregiving, to effectively assist and empower this marginalized carer population.

Genetic optimization of the human gut bacterium Phocaeicola vulgatus for enhanced succinate production

The demand for sustainably produced bulk chemicals is constantly rising. Succinate serves as a fundamental component in various food, chemical, and pharmaceutical products. Succinate can be produced from sustainable raw materials using microbial fermentation and enzyme-based technologies. Bacteroides and Phocaeicola species, widely distributed and prevalent gut commensals, possess enzyme sets for the metabolization of complex plant polysaccharides and synthesize succinate as a fermentative end product. This study employed novel molecular techniques to enhance succinate yields in the natural succinate producer Phocaeicola vulgatus by directing the metabolic carbon flow toward succinate formation. The deletion of the gene encoding the methylmalonyl-CoA mutase (Δmcm, bvu_0309-0310) resulted in a 95% increase in succinate production, as metabolization to propionate was effectively blocked. Furthermore, deletion of genes encoding the lactate dehydrogenase (Δldh, bvu_2499) and the pyruvate:formate lyase (Δpfl, bvu_2880) eliminated the formation of fermentative end products lactate and formate. By overproducing the transketolase (TKT, BVU_2318) in the triple deletion mutant, succinate production increased from 3.9 mmol/g dry weight in the wild type to 10.9 mmol/g dry weight. Overall, succinate yield increased by 180% in the new mutant strain P. vulgatus Δmcm Δldh Δpfl pG106_tkt relative to the parent strain. This approach is a proof of concept, verifying the genetic accessibility of P. vulgatus, and forms the basis for targeted genetic optimization. The increase of efficiency highlights the huge potential of P. vulgatus as a succinate producer with applications in sustainable bioproduction processes.Key points• Deleting methylmalonyl-CoA mutase gene in P. vulgatus doubled succinate production• Triple deletion mutant with transketolase overexpression increased succinate yield by 180%• P. vulgatus shows high potential for sustainable bulk chemical production via genetic optimization

A research agenda to advance the study of implementation mechanisms

BackgroundImplementation science scholars have made significant progress identifying factors that enable or obstruct the implementation of evidence-based interventions, and testing strategies that may modify those factors. However, little research sheds light on how or why strategies work, in what contexts, and for whom. Studying implementation mechanisms—the processes responsible for change—is crucial for advancing the field of implementation science and enhancing its value in facilitating equitable policy and practice change. The Agency for Healthcare Research and Quality funded a conference series to achieve two aims: (1) develop a research agenda on implementation mechanisms, and (2) actively disseminate the research agenda to research, policy, and practice audiences. This article presents the resulting research agenda, including priorities and actions to encourage its execution.MethodBuilding on prior concept mapping work, in a semi-structured, 3-day, in-person working meeting, 23 US-based researchers used a modified nominal group process to generate priorities and actions for addressing challenges to studying implementation mechanisms. During each of the three 120-min sessions, small groups responded to the prompt: “What actions need to be taken to move this research forward?” The groups brainstormed actions, which were then shared with the full group and discussed with the support of facilitators trained in structured group processes. Facilitators grouped critical and novel ideas into themes. Attendees voted on six themes they prioritized to discuss in a fourth, 120-min session, during which small groups operationalized prioritized actions. Subsequently, all ideas were collated, combined, and revised for clarity by a subset of the authorship team.ResultsFrom this multistep process, 150 actions emerged across 10 priority areas, which together constitute the research agenda. Actions included discrete activities, projects, or products, and ways to shift how research is conducted to strengthen the study of implementation mechanisms.ConclusionsThis research agenda elevates actions to guide the selection, design, and evaluation of implementation mechanisms. By delineating recommended actions to address the challenges of studying implementation mechanisms, this research agenda facilitates expanding the field of implementation science, beyond studying what works to how and why strategies work, in what contexts, for whom, and with which interventions.