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Objective: Well-designed patient education materials (PEMs) increase health literacy, which has been linked to better surgical patient outcomes. The quality of lung cancer surgery PEMs is unknown, however. Here we assessed printed lung cancer surgery PEMs for readability, understandability, actionability, and accessibility. Methods: Various lung cancer programs throughout the United States were contacted for their lung cancer surgery PEMs. The readability of the received materials was calculated using 6 readability tests. Four thoracic surgeon–advanced practice practitioner dyads scored the PEMs for understandability, actionability, and accessibility using the Patient Education Material Assessment Tool and the Accessibility Assessment Tool, with the recommended minimum threshold of 70%. One-sample t tests were performed to compare each parameter against its recommended threshold. Results: Out of 34 institutions contacted, 18 (52.9%) provided PEMs. The average reading level of the PEMs ranged from 7th grade to 11th grade, significantly exceeding the recommended 6th grade health literacy threshold (P

Background: : Biobehavioral interventions including relaxation, distraction, and mindfulness meditation exercises have been shown to decrease perioperative stress, anxiety, and pain. Our aims were to 1) quantify pediatric surgical patient-reported pre-operative exposure to and post-operative use of biobehavioral interventions; 2) understand barriers and facilitators to incorporation of biobehavioral interventions into clinical practice; and 3) evaluate associated patient-reported outcomes. Methods: : We conducted an embedded mixed-methods study with a quantitative focus. Data were collected as part of the 18-hospital ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) clinical trial for children, ages 10–18 years, undergoing elective gastrointestinal surgery. Patients/caregivers were surveyed about preoperative exposure to and postoperative use of biobehavioral interventions. Four semi-structured group interviews with 20 pediatric surgery providers were conducted. Outcomes included pain-related functional disability, health-related quality of life (HRQoL), and perioperative nervousness. Results: : 41 % (n = 67) of 164 enrolled patients/caregivers reported preoperative exposure to and 71 % (n = 117) reported postoperative use of a biobehavioral intervention(s). Barriers to incorporation of biobehavioral interventions included lack of standardized workflows, clinician knowledge, and resources. Potential facilitators included media and peer-counseling. After adjusting for individual and hospital characteristics, those who reported using a biobehavioral intervention(s) were 70 % less likely to report worsened postoperative nervousness (95 % CI 0.10–0.91; p = 0.03). Reported use of a biobehavioral intervention(s) was not found to be associated with pain-related functional disability or HRQoL. Conclusions: : Use of a biobehavioral intervention(s) may stabilize postoperative nervousness of children undergoing surgery. There is a need for redesign of clinical workflows and clinician training to facilitate integration of biobehavioral interventions.

Abstract Background For older, frail adults, exercise before surgery through prehabilitation (prehab) may hasten return recovery and reduce postoperative complications. We developed a smartwatch-based prehab program (BeFitMe) for older adults that encourages and tracks at-home exercise. The objective of this study was to assess patient perceptions about facilitators and barriers to prehab generally and to using a smartwatch prehab program among older adult thoracic surgery patients to optimize future program implementation. Methods We recruited patients, aged ≥50 years who had or were having surgery and were screened for frailty (Fried’s Frailty Phenotype) at a thoracic surgery clinic at a single academic institution. Semi-structured interviews were conducted by telephone after obtaining informed consent. Participants were given a description of the BeFitMe program. The interview questions were informed by The Five “Rights” of Clinical Decision-Making framework (Information, Person, Time, Channel, and Format) and sought to identify the factors perceived to influence smartwatch prehab program participation. Interview transcripts were transcribed and independently coded to identify themes in for each of the Five “Rights” domains. Results A total of 29 interviews were conducted. Participants were 52% men (n = 15), 48% Black (n = 14), and 59% pre-frail (n = 11) or frail (n = 6) with a mean age of 68 ± 9 years. Eleven total themes emerged. Facilitator themes included the importance of providers (right person) clearly explaining the significance of prehab (right information) during the preoperative visit (right time); providing written instructions and exercise prescriptions; and providing a preprogrammed and set-up (right format) Apple Watch (right channel). Barrier themes included pre-existing conditions and disinterest in exercise and/or technology. Participants provided suggestions to overcome the technology barrier, which included individualized training and support on usage and responsibilities. Conclusions This study reports the perceived facilitators and barriers to a smartwatch-based prehab program for pre-frail and frail thoracic surgery patients. The future BeFitMe implementation protocol must ensure surgical providers emphasize the beneficial impact of participating in prehab before surgery and provide a written prehab prescription; must include a thorough guide on smartwatch use along with the preprogrammed device to be successful. The findings are relevant to other smartwatch-based interventions for older adults.

Background: Patients newly diagnosed with type 2 diabetes mellitus (DM) and newly prescribed insulin need to learn essential self-care and management skills quickly. To optimize teaching, clinicians need to assess a patient’s basic understanding of DM and their skills. While DM patient assessments exist, this study reports the development of an assessment of patient DM management skills and knowledge, using feedback from DM clinicians, patients, and caregivers. Research Design and Methods: A systematic search of Pubmed/Medline and Scopus (1980–2017) of DM knowledge assessments was performed. Twenty-four studies were identified. Content from the existing assessments was adapted to create a 12 item DM-Skills Knowledge Assessment (SKA) to assess a patient’s DM management skills and knowledge. To assess cultural humility, modified cognitive interviews were conducted in individual user sessions and semi-structured focus groups. Audio-transcripts of the interviews/focus groups were independently coded, and codes were grouped into key themes. Participant demographic characteristics were assessed. Results: Five focus groups and eleven key informant interviews were conducted, including 10 DM clinicians, 12 patients/caregivers, and 15 laypersons. All 10 clinicians reported that the DM-SKA addresses the key domains of DM education deemed to be of highest importance during the transition from hospital to home and that their patients would be willing to complete the assessment. More than half of the patient/caregiver/layperson participants self-reported race/ethnicity other than non-Hispanic white and performed similarly to non-Hispanic white participants in understanding each item, willingness to complete the DM-SKA, and perception that family or community members would be willing to complete the DM-SKA. The DM-SKA has a baseline Flesch reading score of 81.3, indicating low complexity language. Conclusion: DM clinicians agreed that the DM-SKA assesses all essential DM management skills. For patients/caregivers, it has acceptable literacy, cognitive validity, and culturally acceptable for racial/ethnic minority populations in the study, including elderly persons.

Abstract When children are discharged from the hospital after surgery, their caregivers often rely on subjective assessments (e.g., appetite, fatigue) to monitor postoperative recovery as objective assessment tools are scarce at home. Such imprecise and one-dimensional evaluations can result in unwarranted emergency department visits or delayed care. To address this gap in postoperative monitoring, we evaluated the ability of a consumer-grade wearable device, Fitbit, which records multimodal data about daily physical activity, heart rate, and sleep, in detecting abnormal recovery early in children recovering after appendectomy. One hundred and sixty-two children, ages 3–17 years old, who underwent an appendectomy (86 complicated and 76 simple cases of appendicitis) wore a Fitbit device on their wrist for 21 days postoperatively. Abnormal recovery events (i.e., abnormal symptoms or confirmed postoperative complications) that arose during this period were gathered from medical records and patient reports. Fitbit-derived measures, as well as demographic and clinical characteristics, were used to train machine learning models to retrospectively detect abnormal recovery in the two days leading up to the event for patients with complicated and simple appendicitis. A balanced random forest classifier accurately detected 83% of these abnormal recovery days in complicated appendicitis and 70% of abnormal recovery days in simple appendicitis prior to the true report of a symptom/complication. These results support the development of machine learning algorithms to predict onset of abnormal symptoms and complications in children undergoing surgery, and the use of consumer wearables as monitoring tools for early detection of postoperative events.

Abstract Background Rapid-cycle feedback loops provide timely information and actionable feedback to healthcare organizations to accelerate implementation of interventions. We aimed to (1) describe a mixed-method approach for generating and delivering rapid-cycle feedback and (2) explore key lessons learned while implementing an enhanced recovery protocol (ERP) across 18 pediatric surgery centers. Methods All centers are members of the Pediatric Surgery Research Collaborative (PedSRC, www.pedsrc.org ), participating in the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) trial. To assess implementation efforts, we conducted a mixed-method sequential explanatory study, administering surveys and follow-up interviews with each center’s implementation team 6 and 12 months following implementation. Along with detailed notetaking and iterative discussion within our team, we used these data to generate and deliver a center-specific implementation report card to each center. Report cards used a traffic light approach to quickly visualize implementation status (green = excellent; yellow = needs improvement; red = needs significant improvement) and summarized strengths and opportunities at each timepoint. Results We identified several benefits, challenges, and practical considerations for assessing implementation and using rapid-cycle feedback among pediatric surgery centers. Regarding potential benefits, this approach enabled us to quickly understand variation in implementation and corresponding needs across centers. It allowed us to efficiently provide actionable feedback to centers about implementation. Engaging consistently with center-specific implementation teams also helped facilitate partnerships between centers and the research team. Regarding potential challenges, research teams must still allocate substantial resources to provide feedback rapidly. Additionally, discussions and consensus are needed across team members about the content of center-specific feedback. Practical considerations include carefully balancing timeliness and comprehensiveness when delivering rapid-cycle feedback. In pediatric surgery, moreover, it is essential to actively engage all key stakeholders (including physicians, nurses, patients, caregivers, etc.) and adopt an iterative, reflexive approach in providing feedback. Conclusion From a methodological perspective, we identified three key lessons: (1) using a rapid, mixed method evaluation approach is feasible in pediatric surgery and (2) can be beneficial, particularly in quickly understanding variation in implementation across centers; however, (3) there is a need to address several methodological challenges and considerations, particularly in balancing the timeliness and comprehensiveness of feedback. Trial registration NIH National Library of Medicine Clinical Trials. ClinicalTrials.gov Identifier: NCT04060303. Registered August 7, 2019, https://clinicaltrials.gov/ct2/show/NCT04060303

Background: Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood. Objective: To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis. Methods: We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined. Results: A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59). Conclusion: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.

IMPORTANCE:. Characterizing medical interventions delivered to ICU patients over time and their relationship to outcomes can help set expectations and inform decisions made by patients, clinicians, and health systems. OBJECTIVES:. To determine whether distinct and clinically relevant pathways of medical intervention can be identified among adult ICU patients with acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS:. Retrospective observational study using all-payer administrative claims data from 2012 to 2014. Patients were identified from the Healthcare Cost and Utilization Project State Inpatient Databases from Maryland, Massachusetts, Nevada, and Washington. MAIN OUTCOMES AND MEASURES:. Patterns of cumulative medical intervention delivery, over time, using temporal k-means clustering of interventions delivered up to hospital days 0, 5, 10, 20, and up to discharge. RESULTS:. A total of 12,175 admissions were identified and divided into training (75%; n = 9,130) and validation sets (25%; n = 3,045). Without applying a priori classification and using only medical interventions to cluster, we identified three distinct pathways of intervention accounting for 93.5% of training set admissions. We found 45.9% of admissions followed a “cardiac” intervention pathway (e.g., cardiac catheterization, cardioversion); 36.7% followed a “general” pathway (e.g., diagnostic interventions); and 17.4% followed a “prolonged” pathway (e.g., tracheostomy, gastrostomy). Prolonged pathway admissions had longer median hospital length of stay (13 d; interquartile range [IQR], 7.5–18.5 d) compared with cardiac (5; IQR, 2.5–7.5) and general (5; IQR, 3–7). In-hospital death occurred in 24.6% of prolonged pathway admissions compared with 17.9% of cardiac and 6.9% of general. Findings were confirmed in the validation set. CONCLUSIONS AND RELEVANCE:. Most ICU admissions for acute respiratory failure follow one of three clinically relevant pathways of medical intervention which are associated with hospitalization outcomes. This study helps define the longitudinal nature of critical care delivery, which can inform efforts to predict patient outcomes, communicate with patients and their families, and organize critical care resources.

ObjectiveCell-free DNA (cfDNA) prenatal screening is a commercially available noninvasive test that detects fetal genetic material in maternal blood. While expectant parents often use it for “gender” determination, there is little information about unintended consequences of testing, such as revelation of a difference of sex development (DSD). The study aimed to characterize currently available website information about cfDNA and compare the cfDNA-related content.MethodsA systematic search for websites with information about cfDNA was conducted using search terms generated by a natural language processing analysis of the results of an Amazon Mechanical Turk (MTurk) survey of 1,000 parents and then performing a “Google” search, using the terms. Commercial cfDNA testing companies (CC) websites were also identified by consulting a genetic counselor (AGW). Data were collected on about each website’s characteristics and information about cfDNA. Information about cfDNA was compared between websites. Data were analyzed using descriptive statistics, Fisher’s exact test or Kruskal-Wallis test were applied, as appropriate.ResultsSixty websites were identified. After eliminating duplicates, 11 commercial company (CC) websites were identified. Nineteen other websites were reviewed of which six overlapped with five CC websites. Most of the websites had non-professional authors (73.7%), such as laypersons and CC representatives. CC websites were significantly more likely than search term-identified websites to state that cfDNA can screen for trisomy 21 (p=0.002), trisomy 18 (p

Abstract Background Enhanced recovery protocols (ERPs) are an evidence-based intervention to optimize post-surgical recovery. Several studies have demonstrated that the use of an ERP for gastrointestinal surgery results in decreased length of stay, shortened time to a regular diet, and fewer administered opioids, while also trending toward lower complication and 30-day readmission rates. Yet, implementation of ERPs in pediatric surgery is lagging compared to adult surgery. The study’s purpose was to conduct a theory-guided evaluation of barriers and facilitators to ERP implementation at US hospitals with a pediatric surgery service. Methods We conducted semi-structured interviews at 18 hospitals with 48 participants, including pediatric surgeons, anesthesiologists, gastroenterologists, nurses, and physician assistants. Interviews were conducted online, audio-recorded, and transcribed verbatim. To identify barriers and facilitators to ERP implementation, we conducted an analysis using deductive logics based on the five Active Implementation Frameworks (AIFs). Results Effective practices (usable innovations) were challenged by a lack of compliance to ERP elements, and facilitators were having standardized protocols in place and organization support for implementation. Effective implementation (stages of implementation and implementation drivers) had widespread barriers to implementation across the stages from exploration to full implementation. Barriers included needing dedicated teams for ERP implementation and buy-in from hospital leadership. These items, when present, were strong facilitators of effective implementation, in addition to on-site, checklists, protected time to oversee ERP implementation, and order sets for ERP elements built into the electronic medical record. The enabling context (teams) focused on teams’ engagement in ERP implementation and how they collaborated to implement ERPs. Barriers included having surgical team members resistant to change or who were not bought into ERPs in pediatric practice. Facilitators included engaging a multi-disciplinary team and engaging patients and families early in the implementation process. Conclusions Barriers to ERP implementation in pediatric surgery highlighted can be addressed through providing guidelines to ERP implementation, team-based support for change management, and protocols for developing an ERP implementation team. Future steps are to apply and evaluate these strategies in a stepped-wedge, cluster randomized trial to increase the implementation of ERPs at these 18 hospitals.

Background and Aims: Tuberculosis (TB) remains an important global health issue worldwide. Despite this scourge threatening many human lives, especially in developing countries, thus far, no advanced molecular epidemiology study using recent and more accurate tools has been conducted in Mali. Therefore, this study aimed to use variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) technology coupled with the spoligotyping method to accurately determine the hot spots and establish the epidemiological transmission links of TB in Bamako, Mali. Methods: In a cross-sectional study, 245 isolates of Mycobacterium tuberculosis complex (MTBC) were characterized using spoligotyping and MIRU-VNTR, and an epidemiological investigation was conducted. Results: Of the 245 isolates, 184 (75.1%) were formally identified. The most widespread strain was the Cameroon strain (83; 45.1%). Eight major clusters were identified: Ghana (27; 14.7%), West African 2 (22; 12%), Haarlem (13; 7.1%), H37Rv (t) (8; 4.3%), Latin American Mediterranean (8; 4.3%), and Uganda I and II (6; 3.3%). Statistical analysis showed a significant difference between lineages from the respective referral health centers of Bamako, Mali (P = 0.01). Conclusion: This study establishes, for the first time, an accurate spatial distribution of circulating MTB strains in Bamako, Mali. The data was used to identify strains and “hot spots” causing TB infection and can also be used for more targeted public health responses, particularly for hot spots of drug-resistant strains.

Abstract Background The Common Rule Revision (CRR) mandates a single institutional review board (IRB) for all US federally funded nonexempt multisite human participant research. While the CRR aims to improve research efficiency, its success in pediatric research remains uncertain Main body There are multiple challenges that threaten the purported efficiency of the single IRB mandate. While the CRR is clear that ethical review is the purview of the single IRB, responsibility for issues of local study governance are less well defined. Therefore, reliance agreements (RA) must be negotiated between single IRBs and participating institutions. These negotiations can vary significantly based upon the institution’s local context and are often arduous, lengthy, and burdensome. Furthermore, in pediatric research, issues such as assent, surrogate consent, and IRB risk determination add additional layers of complexity that must be considered. No clear system exists for resolving disagreements surrounding these critical human participant protection issues. Finally, the variation in institutional resources directed towards pediatric research may mean that only a select few pediatric institutions will be able to function in the single IRB system. These challenges will need to be overcome to successfully implement the CRR and achieve its objective of improving multisite research efficiency. We suggest that an empiric and collaborative approach utilizing implementation strategies is necessary for the CRR and single IRBs to be effective. Conclusion The CRR seeks to improve the efficiency of multisite human participant research in the US. There are multiple challenges that will need to be overcome. An empiric collaborative approach is necessary. If successful, single IRBs have the potential to usher in a new era of impactful and efficient multisite pediatric research.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT p>0.05. The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Abstract Background Perioperative enhanced recovery protocols (ERPs) have been found to decrease hospital length of stay, in-hospital costs, and complications among adult surgical populations but evidence for pediatric populations is lacking. The study is designed to evaluate the adoption, effectiveness, and generalizability of a 21-element ERP, adapted for pediatric surgery. Methods The multicenter study is a stepped-wedge, cluster-randomized, pragmatic clinical trial that will evaluate the effectiveness of the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) intervention while also assessing site-specific adaptations, implementation fidelity, and sustainability. The target patient population is pediatric patients, between 10 and 18 years old, who undergo elective gastrointestinal surgery. Eighteen (N = 18) participating sites will be randomly assigned to one of three clusters with each cluster, in turn, being randomly assigned to an intervention start period (stepped-wedge). Each cluster will participate in a Learning Collaborative, using the National Implementation Research Network’s five Active Implementation Frameworks (AIFs) (competency, organization, and leadership), as drivers of facilitation of rapid-cycle adaptations and implementation. The primary study outcome is hospital length of stay, with implementation metrics being used to evaluate adoption, fidelity, and sustainability. Additional clinical outcomes include opioid use, post-surgical complications, and post-discharge healthcare utilization (clinic/emergency room visits, telephone calls to clinic, and re-hospitalizations), as well as, assess patient- and parent-reported health-related quality of life outcomes. The protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Discussion The study provides a unique opportunity to accelerate the adoption of ERPs across 18 US pediatric surgical centers and to evaluate, for the first time, the effect of a pediatric-specific ENRICH-US intervention on clinical and implementation outcomes. The study design and methods can serve as a model for future pediatric surgical quality improvement implementation efforts. Trial registration ClinicalTrials.gov NCT04060303 . Registered on 07 August 2019.

Abstract Background Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. Methods We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. Results In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08–4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05–3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15–1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02–1.19; P = 0.01) models. Conclusion The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.

Background. Tobacco use is a modifiable risk factor for cardiovascular events (CVEs) in liver transplant recipients (LTRs), but there is a paucity of data about practitioner adherence to tobacco cessation guidelines for LTRs. We sought to assess adherence to these guidelines as a predictor of CVEs after liver transplant. Methods. We conducted a retrospective, observational, cohort study of adult LTRs from 2010 to 2016 at a large urban, tertiary care transplant network. Results. Of 572 LTRs (mean age‚ 56.9; 64.1% male), 325 (56.8%) were never, 191 (33.4%) were former, and 56 (9.8%) were current tobacco users before liver transplant. Most LTRs (59%) had their tobacco use assessed annually by transplant providers. Among current users, documented tobacco cessation interventions decreased over time‚ and

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.

A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14–1.49), dominant model (OR = 1.36, 95% CI = 1.09–1.70), and additive model (OR = 1.25, 95% CI = 1.09–1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P

Background. Chronic kidney disease (CKD) is associated with cardiovascular (CV) events, a leading complication in liver transplant recipients (LTRs). Timely subspecialty care is associated with improved clinical outcomes in patients with CKD. This study sought to assess associations between nephrology comanagement and CV events among LTRs at risk for or with CKD. Methods. LTRs with CKD plus those at risk were identified in an inception cohort at a single tertiary care network between 2010 and 2016, using electronic health record data and manual chart review. CKD was defined as estimated glomerular filtration rate

Background Patients with acute stroke at non‐ or primary stroke centers (PSCs) are transferred to comprehensive stroke centers for advanced treatments that reduce disability but experience significant delays in treatment and increased adjusted mortality. This study reports the results of a proactive, systematic, risk assessment of the door‐in‐door‐out process and its application to solution design. Methods and Results A learning collaborative (clinicians, patients, and caregivers) at 2 PSCs and 3 comprehensive stroke centers in Chicago, Illinois participated in a failure modes, effects, and criticality analysis to identify steps in the process; failures of each step, underlying causes; and to characterize each failure’s frequency, impact, and safeguards using standardized scores to calculate risk priority and criticality numbers for ranking. Targets for solution design were selected among the highest‐ranked failures. The failure modes, effects, and criticality analysis process map and risk table were completed during in‐person and virtual sessions. Failure to detect severe stroke/large‐vessel occlusion on arrival at the PSC is the highest‐ranked failure and can lead to a 45‐minute door‐in‐door‐out delay caused by failure to obtain a head computed tomography and computed tomography angiogram together. Lower risk failures include communication problems and delays within the PSC team and across the PSC comprehensive stroke center and paramedic teams. Seven solution prototypes were iteratively designed and address 4 of the 10 highest‐ranked failures. Conclusions The failure modes, effects, and criticality analysis identified and characterized previously unrecognized failures of the door‐in‐door‐out process. Use of a risk‐informed approach for solution design is novel for stroke and should mitigate or eliminate the failures.

Background and Purpose: This study aims to determine whether machine learning (ML) and natural language processing (NLP) from electronic health records (EHR) improve the prediction of 30-day readmission after stroke.Methods: Among index stroke admissions between 2011 and 2016 at an academic medical center, we abstracted discrete data from the EHR on demographics, risk factors, medications, hospital complications, and discharge destination and unstructured textual data from clinician notes. Readmission was defined as any unplanned hospital admission within 30 days of discharge. We developed models to predict two separate outcomes, as follows: (1) 30-day all-cause readmission and (2) 30-day stroke readmission. We compared the performance of logistic regression with advanced ML algorithms. We used several NLP methods to generate additional features from unstructured textual reports. We evaluated the performance of prediction models using a five-fold validation and tested the best model in a held-out test dataset. Areas under the curve (AUCs) were used to compare discrimination of each model.Results: In a held-out test dataset, advanced ML methods along with NLP features out performed logistic regression for all-cause readmission (AUC, 0.64 vs. 0.58; p < 0.001) and stroke readmission prediction (AUC, 0.62 vs. 0.52; p < 0.001).Conclusion: NLP-enhanced machine learning models potentially advance our ability to predict readmission after stroke. However, further improvement is necessary before being implemented in clinical practice given the weak discrimination.

The Social Emotional Behavioral (SEB) Team of the National Children's Study (NCS) was tasked with making recommendations for assessment of important aspects of social-emotional health and function in children. This paper describes the constructs recommended for assessment along with the rationale for their assessment. These constructs, representing aspects of Social Relationships, Social Capital, Temperament, Negative Affect, Externalizing Behavior, Social Competence, Self-efficacy, Self-image, Psychological well-being, Ethnic/racial Socialization, Perceived Discrimination, Sexual Orientation, Religiosity, and Perceived Stress and Resilience were identified as being critical to the understanding of children's health and development from birth to age 21.

Abstract Background The shortage of organs for kidney transplantation for patients with end-stage renal disease (ESRD) is magnified in Hispanics/Latin Americans in the United States. Living donor kidney transplantation (LDKT) is the treatment of choice for ESRD. However, compared to their representation on the transplant waitlist, fewer Hispanics receive a LDKT than non-Hispanic whites. Barriers to LDKT for Hispanics include: lack of knowledge, cultural concerns, and language barriers. Few interventions have been designed to reduce LDKT disparities. This study aims to reduce Hispanic disparities in LDKT through a culturally targeted intervention. Methods/Design Using a prospective effectiveness-implementation hybrid design involving pre-post intervention evaluation with matched controls, we will implement a complex culturally targeted intervention at two transplant centers in Dallas, TX and Phoenix, AZ. The goal of the study is to evaluate the effect of Northwestern Medicine’s® Hispanic Kidney Transplant Program’s (HKTP) key culturally targeted components (outreach, communication, education) on Hispanic LDKT rates over five years. The main hypothesis is that exposure to the HKTP will reduce disparities by increasing the ratio of Hispanic to non-Hispanic white LDKTs and the number of Hispanic LDKTs. We will also examine other process and outcome measures including: dialysis patient outreach, education session attendance, marketing efforts, Hispanic patients added to the waitlist, Hispanic potential donors per potential recipient, and satisfaction with culturally competent care. We will use mixed methods based on the Promoting Action on Research Implementation in Health Services (revised PARIHS) and the Consolidated Framework for Implementation Research (CFIR) frameworks to formatively evaluate the fidelity and innovative adaptations to HKTP’s components at both study sites, to identify moderating factors that most affect implementation fidelity, and to identify adaptations that positively and negatively affect outcomes for patients. Discussion Our study will provide new knowledge about implementing culturally targeted interventions and their impact on reducing health disparities. Moreover, the study of a complex organizational-level intervention’s implementation over five years is rare in implementation science; as such, this study is poised to contribute new knowledge to the factors influencing how organizational-level interventions are sustained over time. Trial registration (ClinicalTrials.gov registration # NCT03276390, date of registration: 9–7-17, retrospectively registered)

In Mali, a country in West Africa, cumulative confirmed COVID-19 cases and deaths among healthcare workers (HCWs) remain enigmatically low, despite a series of waves, circulation of SARS-CoV-2 variants, the country’s weak healthcare system, and a general lack of adherence to public health mitigation measures. The goal of the study was to determine whether exposure is important by assessing the seroprevalence of anti-SARS-CoV-2 IgG antibodies in HCWs. The study was conducted between November 2020 and June 2021. HCWs in the major hospitals where COVID-19 cases were being cared for in the capital city, Bamako, Mali, were recruited. During the study period, vaccinations were not yet available. The ELISA of the IgG against the spike protein was optimized and quantitatively measured. A total of 240 HCWs were enrolled in the study, of which seropositivity was observed in 147 cases (61.8%). A continuous increase in the seropositivity was observed, over time, during the study period, from 50% at the beginning to 70% at the end of the study. HCWs who provided direct care to COVID-19 patients and were potentially highly exposed did not have the highest seropositivity rate. Vulnerable HCWs with comorbidities such as obesity, diabetes, and asthma had even higher seropositivity rates at 77.8%, 75.0%, and 66.7%, respectively. Overall, HCWs had high SARS-CoV-2 seroprevalence, likely reflecting a “herd” immunity level, which could be protective at some degrees. These data suggest that the low number of cases and deaths among HCWs in Mali is not due to a lack of occupational exposure to the virus but rather related to other factors that need to be investigated.

Abstract. Introduction:. Recent literature has shown a wide variation in the prescribing patterns of opioids after elective surgery. We conducted an evaluation of discharge opioid prescribing after elective surgical procedures to determine whether opioid-prescribing patterns varied at our institution. Method:. A single academic medical center retrospective review of patients undergoing laparoscopic cholecystectomy, laparoscopic appendectomy, open umbilical hernia repair, simple mastectomy, or thyroidectomy between July 2015 and July 2016. Results:. Among a total of 615 unique surgical cases, we found a wide variation in the number of pills and morphine milligram equivalents prescribed for each procedure evaluated. In addition, 94.8% of all patients discharged received a prescription for opioids, whereas only 15.6% of patients received a prescription for a nonopioid analgesic. Conclusion:. The number and strength of opioids prescribed after surgery can vary widely at a single institution. Further research is needed to elucidate variations in prescribing.

Introduction: Patients with sickle cell disease (SCD) often seek care in emergency departments (EDs) for severe pain. However, there is evidence that they experience inaccurate assessment, suboptimal care, and inadequate follow-up referrals. The aim of this project was to 1) explore the feasibility of applying a failure modes, effects and criticality analysis (FMECA) in two EDs examining four processes of care (triage, analgesic management, high risk/high users, and referrals made) for patients with SCD, and 2) report the failures of these care processes in each ED. Methods: A FMECA was conducted of ED SCD patient care at two hospitals. A multidisciplinary group examined each step of four processes. Providers identified failures in each step, and then characterized the frequency, impact, and safeguards, resulting in risk categorization. Results: Many “high risk” failures existed in both institutions, including a lack of recognition of high-risk or high-user patients and a lack of emphasis on psychosocial referrals. Specific to SCD analgesic management, one setting inconsistently used existing analgesic policies, while the other setting did not have such policies. Conclusion: FMECA facilitated the identification of failures of ED SCD care and has guided quality improvement activities. Interventions can focus on improvements in these specific areas targeting improvements in the delivery and organization of ED SCD care. Improvements should correspond with the forthcoming National Heart, Lung and Blood-sponsored guidelines for treatment of patients with sickle cell disease. [West J Emerg Med. 2014;15(4):446–458.]

The pathogenesis of ricin toxicity following inhalation has been investigated in many animal models, including the non-human primate (predominantly the rhesus macaque), pig, rabbit and rodent. The toxicity and associated pathology described in animal models are broadly similar, but variation appears to exist. This paper reviews the published literature and some of our own unpublished data and describes some of the possible reasons for this variation. Methodological variation is evident, including method of exposure, breathing parameters during exposure, aerosol characteristics, sampling protocols, ricin cultivar, purity and challenge dose and study duration. The model species and strain used represent other significant sources of variation, including differences in macro- and microscopic anatomy, cell biology and function, and immunology. Chronic pathology of ricin toxicity by inhalation, associated with sublethal challenge or lethal challenge and treatment with medical countermeasures, has received less attention in the literature. Fibrosis may follow acute lung injury in survivors. There are advantages and disadvantages to the different models of pulmonary fibrosis. To understand their potential clinical significance, these factors need to be considered when choosing a model for chronic ricin toxicity by inhalation, including species and strain susceptibility to fibrosis, time it takes for fibrosis to develop, the nature of the fibrosis (e.g., self-limiting, progressive, persistent or resolving) and ensuring that the analysis truly represents fibrosis. Understanding the variables and comparative aspects of acute and chronic ricin toxicity by inhalation is important to enable meaningful comparison of results from different studies, and for the investigation of medical countermeasures.

Ricin, produced from the castor beans of Ricinus communis, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab′)2 antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD99 of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab′)2, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication.

BackgroundAt present, parents lack objective methods to evaluate their child’s postoperative recovery following discharge from the hospital. As a result, clinicians are dependent upon a parent’s subjective assessment of the child’s health status and the child’s ability to communicate their symptoms. This subjective nature of home monitoring contributes to unnecessary emergency department (ED) use as well as delays in treatment. However, the integration of data remotely collected using a consumer wearable device has the potential to provide clinicians with objective metrics for postoperative patients to facilitate informed longitudinal, remote assessment. ObjectiveThis multi-institutional study aimed to evaluate the impact of adding actual and simulated objective recovery data that were collected remotely using a consumer wearable device to simulated postoperative telephone encounters on clinicians’ management. MethodsIn total, 3 simulated telephone scenarios of patients after an appendectomy were presented to clinicians at 5 children’s hospitals. Each scenario was then supplemented with wearable data concerning or reassuring against a postoperative complication. Clinicians rated their likelihood of ED referral before and after the addition of wearable data to evaluate if it changed their recommendation. Clinicians reported confidence in their decision-making. ResultsIn total, 34 clinicians participated. Compared with the scenario alone, the addition of reassuring wearable data resulted in a decreased likelihood of ED referral for all 3 scenarios (P

Ricin is a type II ribosome-inactivating toxin that catalytically inactivates ribosomes ultimately leading to cell death. The toxicity of ricin along with the prevalence of castor beans (its natural source) has led to its increased notoriety and incidences of nefarious use. Despite these concerns, there are no licensed therapies available for treating ricin intoxication. Here, we describe the development of a F(ab’)2 polyclonal ovine antitoxin against ricin and demonstrate the efficacy of a single, post-exposure, administration in an in vivo murine model of intoxication against aerosolised ricin. We found that a single dose of antitoxin afforded a wide window of opportunity for effective treatment with 100% protection observed in mice challenged with aerosolised ricin when given 24 h after exposure to the toxin and 75% protection when given at 30 h. Treated mice had reduced weight loss and clinical signs of intoxication compared to the untreated control group. Finally, using imaging flow cytometry, it was found that both cellular uptake and intracellular trafficking of ricin toxin to the Golgi apparatus was reduced in the presence of the antitoxin suggesting both actions can contribute to the therapeutic mechanism of a polyclonal antitoxin. Collectively, the research highlights the significant potential of the ovine F(ab’)2 antitoxin as a treatment for ricin intoxication.

Objective Communication failures between clinicians lead to poor patient outcomes. Critically injured patients have multiple injured organ systems and require complex multidisciplinary care from a wide range of healthcare professionals and communication failures are abundantly common. This study sought to determine barriers and facilitators to interdisciplinary communication between the consulting trauma, intensive care unit (ICU) team and specialty consultants for critically injured patients at an urban, safety-net, level 1 trauma centre.Design An observational qualitative study of barriers and facilitators to interdisciplinary communication.Setting We conducted observations of daily rounds in two trauma surgical ICUs and recorded the most frequently consulted teams.Participants Key informant interviews after presenting clinical vignettes as discussion prompts were conducted with a broad range of clinicians from the ICUs and physicians and nurse practitioners from the consultant teams who were identified during the observations. Interviews were recorded and transcribed verbatim. Data of these 10 interviews were combined with primary transcript data from prior study (25 interviews) and analysed together because of the same setting with same themes. Independent coding of the transcripts, with iterative reconciliation, was performed by two coders.Outcomes measures Facilitators and barriers of interdisciplinary communication were identified.Results A total of 35 interview transcripts were analysed. Cardiology and interventional radiology were the most frequently consulted teams. Consulting and consultant clinicians reported that perceived accessibility from the team seeking a consultation and the consultant team impacted interdisciplinary communication. Accessibility had a physical dimension as well as a psychological dimension. Accessibility was demonstrated by responsiveness between clinicians of different disciplines and in turn facilitated interdisciplinary communication. Social norms, cognitive biases, hierarchy and relationships were reported as both facilitators and barriers to accessibility, and therefore, interdisciplinary communication.Conclusion Accessibility impacted interdisciplinary communication between the consulting and the consultant team.Article summary Elucidates barriers and facilitators to interdisciplinary communication between consulting and consultant teams.

Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC). Methods: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Respiratory Disease Department of The University Teaching Hospital of Point G, in Mali. Findings: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity, specificity, PPV and NPV of 83·3% [66·4-92·6], 96·6% [88·6-99·0], 92·5% [82·3-96·5] and 92·2% [82·7-96·5] and the Xpert had values of 96·7% [83·3-99·4], 80·0% [68·2-88·1], 70·7 [55·5-82·3] and 97·9% [89·3-99·6], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases. Interpretation: Our new Multiplex assay demonstrates better specificity than Xpert for all group studied, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections. Funding: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471) and Northwestern University's Institute for Global Health Catalyzer Fund.

IntroductionOpioids prescribed after surgery accounted for 5% of the 191 million opioid prescriptions filled in 2017. Approximately 80% of the opioid pills prescribed by surgical care providers remain unused, leaving a substantial number of opioids available for non-medical use. We developed a multi-component intervention to address surgical providers’ role in the overprescribing of opioids. Our study will determine effective strategies for reducing post-surgical prescribing while ensuring adequate post-surgery patient-reported pain-related outcomes, and will assess implementation of the strategies.Methods and analysisThe Minimising Opioid Prescribing in Surgery study will implement a multi-component intervention, in an Illinois network of six hospitals (one academical, two large community and three small community hospitals), to decrease opioid analgesics prescribed after surgery. The multi-component intervention involves four domains: (1) patient expectation setting, (2) baseline assessment of opioid use, (3) perioperative pain control optimisation and (4) post-surgical opioid minimisation. Four surgical specialities (general, orthopaedics, urology and gynaecology) at the six hospitals will implement the intervention. A mixed-methods approach will be used to assess the implementation and effectiveness of the intervention. Data from the network’s enterprise data warehouse will be used to evaluate the intervention’s effect on post-surgical prescriptions and a survey will collect pain-related patient-reported outcomes. Intervention effectiveness will be determined using a triangulation design, mixed-methods approach with staggered speciality-specific implementation for contemporaneous control of opioid prescribing changes over time. The Consolidated Framework for Implementation Research will be used to evaluate the site-specific contextual factors and adaptations to achieve implementation at each site.Ethics and disseminationThe study aims to identify the most effective hospital-type and speciality-specific intervention bundles for rapid dissemination into our 56-hospital learning collaborative and in hospitals throughout the USA. All study activities have been approved by the Northwestern University Institutional Review Board (ID STU00205053).