The evolving value assessment of cancer therapies: Results from a modified Delphi study.

The move toward early detection and treatment of cancer presents challenges for value assessment using traditional endpoints. Current cancer management rarely considers the full economic and societal benefits of therapies. Our study used a modified Delphi process to develop principles for defining and assessing value of cancer therapies that aligns with the current trajectory of oncology research and reflects broader notions of value. 24 experts participated in consensus-building activities across 5 months (16 took part in structured interactions, including a survey, plenary sessions, interviews, and off-line discussions, while 8 participated in interviews). Discussion focused on: 1) which oncology-relevant endpoints should be used for assessing treatments for early-stage cancer and access decisions for early-stage treatments, and 2) the importance of additional value components and how these can be integrated in value assessments. The expert group reached consensus on 4 principles in relation to the first area (consider oncology-relevant endpoints other than overall survival; build evidence for endpoints that provide earlier indication of efficacy; develop evidence for the next generation of predictive measures; use managed entry agreements supported by ongoing evidence collection to address decision-maker evidence needs) and 3 principles in relation to the second (routinely use patient reported outcomes in value assessments; assess broad economic impact of new medicines; consider other value aspects of relevance to patients and society).

Implementation of a Novel Chart Rounds Application to Facilitate Peer Review in a Virtual Academic Environment.

Purpose: Peer review in the form of chart rounds is a critical component of quality assurance and safety in radiation therapy treatments. Radiation therapy departments have undergone significant changes that impose challenges to meaningful review, including institutional growth and increasing use of virtual environment. We discuss the implementation of a novel chart rounds (NCR) format and application adapted to modern peer review needs at a single high-volume multisite National Cancer Institute designated cancer center. Methods and Materials: A working group was created to improve upon the prior institutional chart rounds format (standard chart rounds or SCR). Using a novel in-house application and format redesign, an NCR was created and implemented to accomplish stated goals. Data regarding the SCR and NCR system were then extracted for review. Results: SCR consisted of 2- 90-minute weekly sessions held to review plans across all disease sites, review of 49 plans per hour on average. NCR uses 1-hour long sessions divided by disease site, enabling additional time to be spent per patient (11 plans per hour on average) and more robust discussion. The NCR application is able to automate a list of plans requiring peer review from the institutional treatment planning system. The novel application incorporates features that enable efficient and accurate review of plans in the virtual setting across multiple sites. A systematic scoring system is integrated into the application to record feedback. Over 5 months of use of the NCR, 1160 plans have been reviewed with 143 scored as requiring minor changes, 32 requiring major changes and 307 with comments. Major changes triggered treatment replan. Feedback from scoring is incorporated into physician workflow to ensure changes are addressed. Conclusion: The presented NCR format and application enables standardized and highly reliable peer review of radiation therapy plans that is robust across a variety of complex planning scenarios and could be implemented globally.

Recovery of Shoulder, Elbow, and Forearm Movement After Nerve Reconstruction for Neonatal Brachial Plexus Palsy.

BACKGROUND AND OBJECTIVES: There is a relative dearth of published data with respect to recovery of upper extremity movement after nerve reconstruction for neonatal brachial plexus palsy (NBPP). This study aimed to demonstrate long-term recovery of active range of motion (AROM) at the shoulder, elbow, and forearm after nerve reconstruction for NBPP and to compare that with patients managed nonoperatively. METHODS: We interrogated a prospectively collected database of all patients evaluated for NBPP at a single institution from 2005 to 2020. AROM measurements for shoulder, elbow, and forearm movements were collected at every visit up to 5 years of follow-up and normalized between 0 and 1. We used generalized estimated equations to predict AROM for each movement within local age windows over 5 years and compared the operative and nonoperative cohorts at each age interval. RESULTS: In total, >13 000 collected datapoints representing 425 conservatively and 99 operatively managed children were included for analysis. At 5 years, absolute recovery of AROM after nerve reconstruction was ∼50% for shoulder abduction and forward flexion, ∼65% for shoulder external rotation, and ∼75% for elbow flexion and forearm supination, with ∼20% loss of elbow extension AROM. Despite more limited AROM on presentation for the operative cohort, at 5 years, there was no significant difference between the groups in AROM for shoulder external rotation, elbow extension, or forearm supination, and, in Narakas grade 1-2 injury, shoulder abduction and forward flexion. CONCLUSION: We demonstrate recovery of upper extremity AROM after nerve surgery for NBPP. Despite more severe presenting injury, operative patients had similar recovery of AROM when compared with nonoperative patients for shoulder external rotation, elbow extension, forearm supination, and, for Narakas grade 1-2 injury, shoulder abduction and forward flexion.

Quantifying Patient-Initiated Upper Extremity Movement After Surgical Reconstruction for Adult Pan-Brachial Plexus Injury.

BACKGROUND AND OBJECTIVES: Determining functional recovery in adult patients with traumatic pan-brachial plexus injury (pBPI) is hampered by the fact that most outcome measures are collected in the clinical setting and may not reflect arm use in the real world. This study's objectives were to demonstrate the feasibility of using wearable motion sensor technology to quantify spontaneous arm movement in adult patients with pBPI after surgical reconstruction and report the time and intensity with which the affected arm was used. METHODS: Twenty-nine patients with pBPI who underwent surgical reconstruction at least 2 years prior were included in this study. Study participants wore an accelerometer on bilateral arms for 7 days. The vector time (VT) and magnitude with which each arm moved were collected and divided by the same values collected from the uninjured arm to generate a ratio (VT and vector magnitude [VM], respectively) to quantify differences between the arms. Correlations between VT, VM, and patient demographic and physician-elicited clinical measures were calculated. Patients were enrolled at Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan, and data analysis was performed at the University of Michigan. RESULTS: Twelve patients had pan-avulsion injuries, and 17 patients had C5 rupture with C6-T1 avulsion injuries. All underwent nerve reconstruction with contralateral C7 or ipsilateral C5 nerve roots as donors. At mean 7.3 years after surgery, the mean VT ratio was 0.54 ± 0.13 and the mean VM ratio was 0.30 ± 0.13. Both VT and VM ratios were significantly correlated with patient employment and movements at the elbow and forearm. CONCLUSION: Wearable motion detection technology can capture spontaneous, real-world movements of the arm in patients who have undergone surgical reconstruction for pBPI. Despite severe injuries, these patients are able to use their affected arm 50% of the time and with 30% of the intensity of their unaffected arm, which is positively correlated with return to work after injury. These data support the use of surgical reconstruction for pBPI.

The Neutrophil Dynamic Mass Redistribution Assay as a Medium throughput Primary Cell Screening Assay.

In a typical G protein coupled receptor drug discovery campaign, an in vitro primary functional screening assay is often established in a recombinant system overexpressing the target of interest, which offers advantages with respect to overall throughput and robustness of compound testing. Subsequently, compounds are then progressed into more physiologically relevant but lower throughput ex vivo primary cell assays and finally in vivo studies. Here we describe a dynamic mass redistribution (DMR) assay that has been developed in a format suitable to support medium throughput drug screening in primary human neutrophils. Neutrophils are known to express both CXC chemokine receptor (CXCR) 1 and CXCR2 that are thought to play significant roles in various inflammatory disorders and cancer. Using multiple relevant chemokine ligands and a range of selective and nonselective small and large molecule antagonists that block CXCR1 and CXCR2 responses, we demonstrate distinct pharmacological profiles in neutrophil DMR from those observed in recombinant assays but predictive of activity in neutrophil chemotaxis and CD11b upregulation, a validated target engagement marker previously used in clinical studies of CXCR2 antagonists. The primary human neutrophil DMR cell system is highly reproducible, robust, and less prone to donor variability observed in CD11b and chemotaxis assays and thus provides a unique, more physiologically relevant, and higher throughput assay to support drug discovery and translation to early clinical trials. SIGNIFICANCE STATEMENT: Neutrophil dynamic mass redistribution assays provide a higher throughput screening assay to profile compounds in primary cells earlier in the screening cascade enabling a higher level of confidence in progressing the development of compounds toward the clinic. This is particularly important for chemokine receptors where redundancy contributes to a lack of correlation between recombinant screening assays and primary cells, with the coexpression of related receptors confounding results.

Validation of a real-time PCR panel for detection and quantification of nine pathogens commonly associated with canine infectious respiratory disease.

Canine infectious respiratory disease (CIRD) is a complicated respiratory syndrome in dogs [1], [2], [3]. A panel PCR was developed [4] to detect nine pathogens commonly associated with CIRD: Mycoplasma cynos, Mycoplasma canis, Bordetella bronchiseptica; canine adenovirus type 2, canine herpesvirus 1, canine parainfluenza virus, canine distemper virus, canine influenza virus and canine respiratory coronavirus [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. To evaluate diagnostic performance of the assay, 740 nasal swab and lung tissue samples were collected and tested with the new assay, and compared to an older version of the assay detecting the same pathogens except that it does not differentiate the two Mycoplasma species. Results indicated that the new assay had the same level of specificity, but with higher diagnostic sensitivity and had identified additional samples with potential co-infections. To confirm the new assay is detecting the correct pathogens, samples with discrepant results between the two assays were sequence-confirmed. Spiking a high concertation target to samples carrying lower concentrations of other targets was carried out and the results demonstrated that there was no apparent interference among targets in the same PCR reaction. Another spike-in experiment was used to determine detection sensitivity between nasal swab and lung tissue samples, and similar results were obtained.•A nine-pathogen CIRD PCR panel assay had identified 139 positives from 740 clinical samples with 60 co-infections;•High-concentration target does not have apparent effect on detecting low-concentration targets;•Detection sensitivity were similar between nasal swab and lung tissue samples.

Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy.

Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.

Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy.

The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% (n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.

Patterns and cost of care according to keratinocyte cancer risk stratification in a volunteer population screening clinic: Real-world data from the TRoPICS study.

BACKGROUND: Risk prediction tools have been developed for keratinocyte cancers (KCs) to effectively categorize individuals with different levels of skin cancer burden. Few have been clinically validated nor routinely used in clinical settings. OBJECTIVES: To assess whether risk prediction tool categories associate with interventions including chemoprophylaxis for skin cancer, and health-care costs in a dermatologist-run screening clinic. METHODS: Adult participants who presented to a walk-in screening facility were invited to participate. A self-completed KC risk prediction tool was used to classify participants into one of the five risk categories. Participants subsequently underwent full skin examination by a dermatologist. Dermatological interventions and skin cancer-related medical prescriptions were documented. Total health-care costs, both to the health-care system and patients were evaluated. RESULTS: Of the 507 participants recruited, 5-fluorouracil cream and nicotinamide were more frequently prescribed in the higher risk groups as chemoprophylaxis (p < 0.005). A significant association with high predicted risk was also observed in the use of cryotherapy and curettage and cautery (p < 0.05). The average health-care costs associated with a skin check visit increased from $90 ± 37 (standard deviation) in the lowest risk group to $149 ± 97 in the highest risk group (p < 0.0001). CONCLUSIONS: We observed a positive association between higher predicted risk of skin cancer and the prescription of chemoprophylaxis and health-care costs involved with opportunistic community skin cancer screening. A clinical use of risk stratification may be to provide an opportunity for clinicians to discuss skin cancer prevention and chemoprophylaxis with individual patients.

Overcoming Barriers to Tobacco Cessation and Lung Cancer Screening among Racial and Ethnic Minority Groups and Underserved Patients in Academic Centers and Community Network Sites: The City of Hope Experience.

BACKGROUND: Tobacco control is important for cancer patient health, but delivering effective low-dose CT (LDCT) screening and tobacco cessation is more difficult in underserved and patients from racial and ethnic minority groups. At City of Hope (COH), we have developed strategies to overcome barriers to the delivery of LDCT and tobacco cessation. METHODS: We performed a needs assessment. New tobacco control program services were implemented focusing on patients from racial and ethnic minority groups. Innovations included Whole Person Care with motivational counseling, placing clinician and nurse champions at points of care, training module and leadership newsletters, and a patient-centric personalized medicine Personalized Pathways to Success (PPS) program. RESULTS: Emphasis on patients from racial and ethnic minority groups was implemented by training cessation personnel and lung cancer control champions. LDCT increased. Tobacco use assessment increased and abstinence was 27.2%. The PPS pilot program achieved 47% engagement in cessation, with self-reported abstinence at 3 months of 38%, with both results slightly higher in patients from racial and ethnic minority groups than in Caucasian patients. CONCLUSIONS: Tobacco cessation barrier-focused innovations can result in increased lung cancer screening and tobacco cessation reach and effectiveness, especially among patients from racial and ethnic minority groups. The PPS program is promising as a personalized medicine patient-centric approach to cessation and lung cancer screening.

Increasing clinician participation in tobacco cessation by an implementation science-based tobacco cessation champion program.

BACKGROUND: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. METHODS: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. RESULTS: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. CONCLUSION: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network.

Development of a three-panel multiplex real-time PCR assay for simultaneous detection of nine canine respiratory pathogens.

Infectious respiratory disease is one of the most common diseases in dogs worldwide. Several bacterial and viral pathogens can serve as causative agents of canine infectious respiratory disease (CIRD), including Mycoplasma cynos, Mycoplasma canis, Bordetella bronchiseptica, canine adenovirus type 2 (CAdV-2), canine herpesvirus 1 (CHV-1), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine influenza virus (CIA) and canine respiratory coronavirus (CRCoV). Since these organisms cause similar clinical symptoms, disease diagnosis based on symptoms alone can be difficult. Therefore, a quick and accurate test is necessary to rapidly identify the presence and relative concentrations of causative CIRD agents. In this study, a multiplex real-time PCR panel assay was developed and composed of three subpanels for detection of the aforementioned pathogens. Correlation coefficients (R2) were >0.993 for all singleplex and multiplex real-time PCR assays with the exception of one that was 0.988; PCR amplification efficiencies (E) were between 92.1% and 107.8% for plasmid DNA, and 90.6-103.9% for RNA templates. In comparing singular and multiplex PCR assays, the three multiplex reactions generated similar R2 and E values to those by corresponding singular reactions, suggesting that multiplexing did not interfere with the detection sensitivities. The limit of detection (LOD) of the multiplex real-time PCR for DNA templates was 5, 2, 3, 1, 1, 1, 4, 24 and 10 copies per microliter for M. cynos, M. canis, B. brochiseptica, CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively; and 3, 2, 6, 17, 4 and 8 copies per microliter for CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively, when RNA templates were used for the four RNA viruses. No cross-detection was observed among the nine pathogens. For the 740 clinical samples tested, the newly designed PCR assay showed higher diagnostic sensitivity compared to an older panel assay; pathogen identities from selected samples positive by the new assay but undetected by the older assay were confirmed by Sanger sequencing. Our data showed that the new assay has higher diagnostic sensitivity while maintaining the assay's specificity, as compared to the older version of the panel assay.

A Web-Based mHealth Intervention With Telephone Support to Increase Physical Activity Among Pregnant Patients With Overweight or Obesity: Feasibility Randomized Controlled Trial.

BACKGROUND: Pregnant patients with overweight or obesity are at high risk for perinatal complications. Excess gestational weight gain (GWG) further exacerbates this risk. Mobile health (mHealth) lifestyle interventions that leverage technology to facilitate self-monitoring and provide just-in-time feedback may motivate behavior change to reduce excess GWG, reduce intervention costs, and increase scalability by improving access. OBJECTIVE: This study aimed to test the acceptability and feasibility of a pilot mHealth lifestyle intervention for pregnant patients with overweight or obesity to promote moderate intensity physical activity (PA), encourage guideline-concordant GWG, and inform the design of a larger pragmatic cluster randomized controlled trial. METHODS: We conducted a mixed methods acceptability and feasibility randomized controlled trial among pregnant patients with a prepregnancy BMI of 25 to 40 kg/m2. Patients with singletons at 8 to 15 weeks of gestation who were aged ≥21 years and had Wi-Fi access were recruited via email from 2 clinics within Kaiser Permanente Northern California and randomized to receive usual prenatal care or an mHealth lifestyle intervention. Participants in the intervention arm received wireless scales, access to an intervention website, activity trackers to receive automated feedback on weight gain and activity goals, and monthly calls from a lifestyle coach. Surveys and focus groups with intervention participants assessed intervention satisfaction and ways to improve the intervention. PA outcomes were self-assessed using the Pregnancy Physical Activity Questionnaire, and GWG was assessed using electronic health record data for both arms. RESULTS: Overall, 33 patients were randomly assigned to the intervention arm, and 35 patients were randomly assigned to the usual care arm. All participants in the intervention arm weighed themselves at least once a week, compared with 20% (7/35) of the participants in the usual care arm. Participants in the intervention arm wore the activity tracker 6.4 days per week and weighed themselves 5.3 times per week, and 88% (29/33) of them rated the program "good to excellent." Focus groups found that participants desired more nutrition-related support to help them manage GWG and would have preferred an app instead of a website. Participants in the intervention arm had a 23.46 metabolic equivalent of task hours greater change in total PA per week and a 247.2-minute greater change in moderate intensity PA per week in unadjusted models, but these effects were attenuated in adjusted models (change in total PA: 15.55 metabolic equivalent of task hours per week; change in moderate intensity PA: 199.6 minutes per week). We found no difference in total GWG (mean difference 1.14 kg) compared with usual care. CONCLUSIONS: The pilot mHealth lifestyle intervention was feasible, highly acceptable, and promoted self-monitoring. Refined interventions are needed to effectively affect PA and GWG among pregnant patients with overweight or obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03936283; https://clinicaltrials.gov/ct2/show/NCT03936283.

Quantifying long-term upper-limb activity using wearable motion sensors after nerve reconstruction for neonatal brachial plexus palsy.

OBJECTIVE: Standard, physician-elicited clinical assessment tools for the evaluation of function after nerve reconstruction for neonatal brachial plexus palsy (NBPP) do not accurately reflect real-world arm function. Wearable activity monitors allow for the evaluation of patient-initiated, spontaneous arm movement during activities of daily living. In this pilot study, the authors demonstrate the feasibility of using body-worn sensor technology to quantify spontaneous arm movement in children with NBPP 10 years after nerve reconstruction and report the timing and magnitude of recovered arm movement. METHODS: Eight children with NBPP who underwent brachial plexus reconstruction approximately 10 years prior were recruited to take part in this single-institution prospective pilot study. Per the treatment protocol of the authors' institution, operated patients had severe, nonrecovering nerve function at the time of surgery. The patients were fitted with an activity monitoring device on each of the affected and unaffected arms, which were worn for 7 consecutive days. The duration (VT) and power (VM) with which each arm moved during the patient's normal daily activities were extracted from the accelerometry data and ratios comparing the affected and unaffected arms were calculated. Demographic data and standard physician-elicited clinical measures of upper-extremity function were also collected. RESULTS: Three children underwent nerve grafting and transfer and 5 children underwent graft repair only. The mean (± SD) active range of motion was 98° ± 53° for shoulder abduction, 130° ± 24° for elbow flexion, and 39° ± 34° for shoulder external rotation. The median Medical Research Council grade was at least 2.5 for all muscle groups. The median Mallet grade was at least 2 for all categories, and 13.5 total. The VT ratio was 0.82 ± 0.08 and the VM ratio was 0.53 ± 0.12. CONCLUSIONS: Wearable activity monitors such as accelerometers can be used to quantify spontaneous arm movement in children who underwent nerve reconstruction for NBPP at long-term follow-up. These data more accurately reflect complex, goal-oriented movement needed to perform activities of daily living. Notably, despite severe, nonrecovering nerve function early in life, postsurgical NBPP patients use their affected arms more than 80% of the time that they use their unaffected arms, paralleling results in patients with NBPP who recovered spontaneously. These data represent the first long-term, real-world evidence to support brachial plexus reconstruction for patients with NBPP.

Virtual Away Rotations Increase Access to Radiation Oncology.

The COVID-19 pandemic altered the workplace for medical education. As restrictions ease, the opportunities provided by virtual rotations remain. Radiation oncology rotations based on virtual participation with patients (consultations, follow-ups, and brachytherapy), contouring and reviewing external beam plans, didactics, and unstructured office hours have been well received at multiple institutions. Virtual rotations decrease barriers to access including lack of a radiation oncology department at one's home institute and the high cost of travel and housing. Furthermore, rotations can be adapted to preclinical students and those with prior radiation oncology rotation experience. However, the virtual format creates and exacerbates several challenges including technical difficulties with electronic medical record or treatment planning software, lack of the spontaneous interactions common to in-person rotations, and unexpected delays in the clinic. We recommend early scheduled time with information technology services to troubleshoot any potential issues, scheduled office hours with faculty and videoconferencing with nonphysician team members to mitigate omission of in-person introductions, and provision of complete contact information for all staff scheduled to meet with students to facilitate communication when unexpected clinic issues arise. Although we are all excited for quarantine restrictions to safely be lifted, we support the continued development of virtual away rotations as a flexible, more affordable option to increase exposure to the field.

Whole-genome classification of rotavirus C and genetic diversity of porcine strains in the USA.

Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19-G31, P[22]-P[26], R5, A9-A12, N9-N10, T7-T9 and E6-E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.

Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study.

BACKGROUND: Preterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown. OBJECTIVES: We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk. METHODS: This prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery <37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score <75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors. RESULTS: One hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs. CONCLUSIONS: A healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.