Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test.

AIMS/HYPOTHESIS: Exercise has a profound effect on insulin sensitivity in skeletal muscle. The euglycaemic-hyperinsulinaemic clamp (EHC) is the gold standard for assessment of insulin sensitivity but it does not reflect the hyperglycaemia that occurs after eating a meal. In previous EHC investigations, it has been shown that the interstitial glucose concentration in muscle is decreased to a larger extent in previously exercised muscle than in rested muscle. This suggests that previously exercised muscle may increase its glucose uptake more than rested muscle if glucose supply is increased by hyperglycaemia. Therefore, we hypothesised that the exercise-induced increase in muscle insulin sensitivity would appear greater after eating a meal than previously observed with the EHC. METHODS: Ten recreationally active men performed dynamic one-legged knee extensor exercise for 1 h. Following this, both femoral veins and one femoral artery were cannulated. Subsequently, 4 h after exercise, a solid meal followed by two liquid meals were ingested over 1 h and glucose uptake in the two legs was measured for 3 h. Muscle biopsies from both legs were obtained before the meal test and 90 min after the meal test was initiated. Data obtained in previous studies using the EHC (n=106 participants from 13 EHC studies) were used for comparison with the meal-test data obtained in this study. RESULTS: Plasma glucose and insulin peaked 45 min after initiation of the meal test. Following the meal test, leg glucose uptake and glucose clearance increased twice as much in the exercised leg than in the rested leg; this difference is twice as big as that observed in previous investigations using EHCs. Glucose uptake in the rested leg plateaued after 15 min, alongside elevated muscle glucose 6-phosphate levels, suggestive of compromised muscle glucose metabolism. In contrast, glucose uptake in the exercised leg plateaued 45 min after initiation of the meal test and there were no signs of compromised glucose metabolism. Phosphorylation of the TBC1 domain family member 4 (TBC1D4; p-TBC1D4Ser704) and glycogen synthase activity were greater in the exercised leg compared with the rested leg. Muscle interstitial glucose concentration increased with ingestion of meals, although it was 16% lower in the exercised leg than in the rested leg. CONCLUSIONS/INTERPRETATION: Hyperglycaemia after meal ingestion results in larger differences in muscle glucose uptake between rested and exercised muscle than previously observed during EHCs. These findings indicate that the ability of exercise to increase insulin-stimulated muscle glucose uptake is even greater when evaluated with a meal test than has previously been shown with EHCs.

Sagittal and transverse ankle angle coupling can influence prosthetic socket transverse plane moments.

Introduction: The intact foot and ankle comprise a complex set of joints that allow rotation in multiple planes of motion. Some of these motions are coupled, meaning rotation in one plane induces motion in another. One such coupling is between the sagittal and transverse planes. For every step, plantar- and dorsi-flexion motion is coupled with external and internal rotation of the shank relative to the foot, respectively. There is no prosthetic foot available for prescription that mimics this natural coupling. The purpose of this study was to determine if a sagittal:transverse ankle angle coupling ratio exists that minimizes the peak transverse plane moment during prosthetic limb stance. Methods: A novel, torsionally active prosthesis (TAP) was used to couple sagittal and transverse plane motions using a 60-watt motor. An embedded controller generated transverse plane rotation trajectories proportional to sagittal plane ankle angles corresponding to sagittal:transverse coupling ratios of 1:0 (rigid coupling analogous to the standard-of-care), 6:1, 4:1, 3:1, and 2:1. Individuals with unilateral transtibial amputation were block randomized to walk in a straight line and in both directions around a 2 m circle at their self-selected speed with the TAP set at randomized coupling ratios. The primary outcome was the peak transverse plane moment, normalized to body mass, during prosthetic limb stance. Secondary outcomes included gait biomechanic metrics and a measure of satisfaction. Results: Eleven individuals with unilateral transtibial amputations participated in the study. The 6:1 coupling ratio resulted in reduced peak transverse plane moments in pairwise comparisons with 3:1 and 2:1 coupling ratios while walking in a straight line and with the prosthesis on the outside of the circle (p < .05). Coupling ratio had no effect on gait biomechanic metrics or satisfaction. Discussion: The general pattern of results suggests a quadratic relationship between the peak transverse plane moment and coupling ratio with a minimum at the 6:1 coupling ratio. The coupling ratio did not appear to adversely affect propulsion or body support. Subjects indicated they found all coupling ratios to be comfortable. While a mechatronic prosthesis like the TAP may have limited commercial potential, our future work includes testing a robust, passive prosthetic foot with a fixed coupling ratio.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Influence of Walking Over Unexpected Uneven Terrain on Joint Loading for Individuals With Transtibial Amputation.

Individuals with transtibial amputation (TTA) experience asymmetric lower-limb loading which can lead to joint pain and injuries. However, it is unclear how walking over unexpected uneven terrain affects their loading patterns. This study sought to use modeling and simulation to determine how peak joint contact forces and impulses change for individuals with unilateral TTA during an uneven step and subsequent recovery step and how those patterns compare to able-bodied individuals. We expected residual limb loading during the uneven step and intact limb loading during the recovery step would increase relative to flush walking. Further, individuals with TTA would experience larger loading increases compared to able-bodied individuals. Simulations of individuals with TTA showed during the uneven step, changes in joint loading occurred at all joints except the prosthetic ankle relative to flush walking. During the recovery step, intact limb joint loading increased in early stance relative to flush walking. Simulations of able-bodied individuals showed large increases in ankle joint loading for both surface conditions. Overall, increases in early stance knee joint loading were larger for those with TTA compared to able-bodied individuals during both steps. These results suggest that individuals with TTA experience altered joint loading patterns when stepping on uneven terrain. Future work should investigate whether an adapting ankle-foot prosthesis can mitigate these changes to reduce injury risk.

Streamlining the Generation of Advanced Polymer Materials Through the Marriage of Automation and Multiblock Copolymer Synthesis in Emulsion.

Synthetic polymers are of paramount importance in modern life - an incredibly wide range of polymeric materials possessing an impressive variety of properties have been developed to date. The recent emergence of artificial intelligence and automation presents a great opportunity to significantly speed up discovery and development of the next generation of advanced polymeric materials. We have focused on the high-throughput automated synthesis of multiblock copolymers that comprise three or more distinct polymer segments of different monomer composition bonded in linear sequence. The present work has exploited automation to prepare high molar mass multiblock copolymers (typically>100,000 g mol-1) using reversible addition-fragmentation chain transfer (RAFT) polymerization in aqueous emulsion. A variety of original multiblock copolymers have been synthesised via a Chemspeed robot, exemplified by a multiblock copolymer comprising thirteen constituent blocks. Moreover, libraries of copolymers of randomized monomer compositions (acrylates, acrylamides, methacrylates, and styrenes), block orders, and block lengths were also generated, thereby demonstrating the robustness of our synthetic approach. One multiblock copolymer contained all four monomer families listed in the pool, which is unprecedented in the literature. The present work demonstrates that automation has the power to render complex and laborious syntheses of such unprecedented materials not just possible, but facile and straightforward, thus representing the way forward to the next generation of complex macromolecular architectures.

The Influence of Multiple Pregnancies on Gait Asymmetry: A Case Study.

Gait asymmetry is a predictor of fall risk and may contribute to increased falls during pregnancy. Previous work indicates that pregnant women experience asymmetric joint laxity and pelvic tilt during standing and asymmetric joint moments and angles during walking. How these changes translate to other measures of gait asymmetry remains unclear. Thus, the purpose of this case study was to determine the relationships between pregnancy progression, subsequent pregnancies, and gait asymmetry. Walking data were collected from an individual during 2 consecutive pregnancies during the second and third trimesters and 6 months postpartum of her first pregnancy and the first, second, and third trimesters and 6 months postpartum of her second pregnancy. Existing asymmetries in step length, anterior-posterior (AP) impulses, AP peak ground reaction forces, lateral impulses, and joint work systematically increased as her pregnancy progressed. These changes in asymmetry may be attributed to pelvic asymmetry, leading to asymmetric hip flexor and extensor length, or due to asymmetric plantar flexor strength, as suggested by her ankle work asymmetry. Relative to her first pregnancy, she had greater asymmetry in step length, step width, braking AP impulse, propulsive AP impulse, and peak braking AP ground reaction force during her second pregnancy, which may have resulted from increased joint laxity.

Winter residency and foraging of non-native round goby populations in Great Lakes tributary streams.

Investigations of winter diets and foraging in fish are rare, and less so for migratory species in the temperate zone. In the Great Lakes, the round goby (Neogobius melanostomus) is known to out-migrate from nearshore habitats to offshore depths in the winter months. However, in Great Lake tributaries, populations of this fish were found up to 25 km upstream during winter months. Distance upstream was a predictor of out-migration behavior with populations farthest upstream remaining as winter residents, whereas populations nearest the lakes out-migrated. Distance inland was also a predictor of fish total length, but not Fulton's condition index. Seasonal resources and local prey availability shaped the diets of these fish, but resource use remained unchanged over time since invasion. Total length and body condition also remained unchanged over time since the invasion. Plasticity in both diet and migration behavior seems to be beneficial traits for the inland invasion success of this fish.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Association of Direct Oral Anticoagulation Management Strategies With Clinical Outcomes for Adults With Atrial Fibrillation.

Importance: Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF). Objective: To compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF. Design, Setting, and Participants: This retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023. Exposures: Each KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions. Main Outcomes and Measures: Patients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020. Results: Overall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group. Conclusions and Relevance: This cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.

Costs and Consequences of a Novel Emergency Department Sepsis Diagnostic Test: The IntelliSep Index.

Sepsis causes 270,000 deaths and costs $38 billion annually in the United States. Most cases of sepsis present in the emergency department (ED), where rapid diagnosis remains challenging. The IntelliSep Index (ISI) is a novel diagnostic test that analyzes characteristics of WBC structure and provides a reliable early signal for sepsis. This study performs a cost-consequence analysis of the ISI relative to procalcitonin for early sepsis diagnosis in the ED. PERSPECTIVE: U.S. healthcare system. SETTING: Community hospital ED. METHODS: A decision tree analysis was performed comparing ISI with procalcitonin. Model parameters included prevalence of sepsis, sensitivity and specificity of diagnostic tests (both ISI and procalcitonin), costs of hospitalization, and mortality rate stratified by diagnostic test result. Mortality and prevalence of sepsis were estimated from best available literature. Costs were estimated based on an analysis of a large, national discharge dataset, and adjusted to 2018 U.S. dollars. Outcomes included expected costs and survival. RESULTS: Assuming a confirmed sepsis prevalence of 16.9% (adjudicated to Sepsis-3), the ISI strategy had an expected cost per patient of $3,849 and expected survival rate of 95.08%, whereas the procalcitonin strategy had an expected cost of $4,656 per patient and an expected survival of 94.98%. ISI was both less costly and more effective than procalcitonin, primarily because of fewer false-negative results. These results were robust in sensitivity analyses. CONCLUSIONS: ISI was both less costly and more effective in preventing mortality than procalcitonin, primarily because of fewer false-negative results. The ISI may provide health systems with a higher-value diagnostic test in ED sepsis evaluation. Additional work is needed to validate these results in clinical practice.

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer.

Background: Reduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls. Methods: Age-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise. Results: At 0 h, conventional T cell counts increased by 45%-64% with no differences between groups. T cell frequency decreased by -3.5% for CD3+ and -4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of -4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was -18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h. Conclusion: Following acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. Results: We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients' tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. Conclusions: We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and Implications: Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients' RNA-seq and clinical data, we found the signature genes - with epigenetic and transcriptomic dysregulation - associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.

Biomechanical responses of individuals with transtibial amputation stepping on a coronally uneven and unpredictable surface.

Coronally uneven surfaces are prevalent in natural and man-made terrain, such as holes or bumps in the ground, curbs, sidewalks, and driveways. These surfaces can be challenging to navigate, especially for individuals with lower limb amputations. This study examined the biomechanical response of individuals with unilateral transtibial amputation (TTA) taking a step on a coronally uneven surface while wearing their clinically prescribed prosthesis, compared to individuals without mobility impairments (controls). An instrumented walkway was used with the middle force plate positioned either flush or rotated ± 15˚ in the coronal plane and concealed (blinded). TTAs used greater hip abduction compared to controls across all conditions, but especially during blinded inversion. The recovery step width of TTAs was wider after blinded eversion and narrower after blinded inversion, but unchanged for controls. These results suggest TTAs may have decreased balance control on unexpected, uneven surfaces. Additionally, TTAs generated less positive prosthetic ankle joint work during blinded inversion and eversion, and less negative coronal hip joint work during blinded inversion compared to controls. These biomechanical responses could lead to increased energy expenditure on uneven terrain. Surface condition had no effect on the vertical center of mass for either group of participants. Finally, the TTAs and the control group generated similar vertical GRF impulses, suggesting the TTAs had sufficient body support despite differences in surface conditions. These results are important to consider for future prosthetic foot designs and rehabilitation strategies.

Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US.

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.

Multiblock copolymer synthesis via RAFT emulsion polymerization.

A multiblock copolymer is a polymer of a specific structure that consists of multiple covalently linked segments, each comprising a different monomer type. The control of the monomer sequence has often been described as the "holy grail" of synthetic polymer chemistry, with the ultimate goal being synthetic access to polymers of a "perfect" structure, where each monomeric building block is placed at a desired position along the polymer chain. Given that polymer properties are intimately linked to the microstructure and monomer distribution along the constituent chains, it goes without saying that there exist seemingly endless opportunities in terms of fine-tuning the properties of such materials by careful consideration of the length of each block, the number and order of blocks, and the inclusion of monomers with specific functional groups. The area of multiblock copolymer synthesis remains relatively unexplored, in particular with regard to structure-property relationships, and there are currently significant opportunities for the design and synthesis of advanced materials. The present review focuses on the synthesis of multiblock copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization implemented as aqueous emulsion polymerization. RAFT emulsion polymerization offers intriguing opportunities not only for the advanced synthesis of multiblock copolymers, but also provides access to polymeric nanoparticles of specific morphologies. Precise multiblock copolymer synthesis coupled with self-assembly offers material morphology control on length scales ranging from a few nanometers to a micrometer. It is imperative that polymer chemists interact with physicists and material scientists to maximize the impact of these materials of the future.

Assessment of aerosol persistence in ICUs via low-cost sensor network and zonal models.

The COVID-19 pandemic raised public awareness about airborne particulate matter (PM) due to the spread of infectious diseases via the respiratory route. The persistence of potentially infectious aerosols in public spaces and the spread of nosocomial infections in medical settings deserve careful investigation; however, a systematic approach characterizing the fate of aerosols in clinical environments has not been reported. This paper presents a methodology for mapping aerosol propagation using a low-cost PM sensor network in ICU and adjacent environments and the subsequent development of the data-driven zonal model. Mimicking aerosol generation by a patient, we generated trace NaCl aerosols and monitored their propagation in the environment. In positive (closed door) and neutral-pressure (open door) ICUs, up to 6% or 19%, respectively, of all PM escaped through the door gaps; however, the outside sensors did not register an aerosol spike in negative-pressure ICUs. The K-means clustering analysis of temporospatial aerosol concentration data suggests that ICU can be represented by three distinct zones: (1) near the aerosol source, (2) room periphery, and (3) outside the room. The data suggests two-phase plume behavior: dispersion of the original aerosol spike throughout the room, followed by an evacuation phase where "well-mixed" aerosol concentration decayed uniformly. Decay rates were calculated for positive, neutral, and negative pressure operations, with negative-pressure rooms clearing out nearly twice as fast. These decay trends closely followed the air exchange rates. This research demonstrates the methodology for aerosol monitoring in medical settings. This study is limited by a relatively small data set and is specific to single-occupancy ICU rooms. Future work needs to evaluate medical settings with high risks of infectious disease transmission.

Impact of COVID-19 on Trends in Outpatient Clinic Utilization: A Tale of 2 Departments.

BACKGROUND: The COVID-19 pandemic forced many US health care organizations to shift from mostly in-person care to a hybrid of virtual visits (VV) and in-person visits (IPV). While there was an expected and immediate shift to virtual care (VC) early in the pandemic, little is known about trends in VC use after restrictions eased. METHODS: This is a retrospective study using data from 3 health care systems. All completed visits from adult primary care (APC) and behavioral health (BH) were extracted from the electronic health record of adults aged 19 years and older from January 1, 2019 to June 30, 2021. Standardized weekly visit rates were calculated by department and site and analyzed using time series analysis. RESULTS: There was an immediate decrease in APC visits following the onset of the pandemic. IPV were quickly replaced by VV such that VV accounted for most APC visits early in the pandemic. By 2021, VV rates declined, and VC visits accounted for <50% of all APC visits. By Spring 2021, all 3 health care systems saw a resumption of APC visits as rates neared or returned to prepandemic levels. In contrast, BH visit rates remained constant or slightly increased. By April 2020, almost all BH visits were being delivered virtually at each of the 3 sites and continue to do so without changes to utilization. CONCLUSIONS: VC use peaked during the early pandemic period. While rates of VC are higher than prepandemic levels, IPV are the predominant visit type in APC. In contrast, VC use has sustained in BH, even after restrictions eased.

Management of Neck or Back Pain in Ambulatory Care: Did Visit Mode or the COVID-19 Pandemic Affect Provider Practice or Patient Adherence?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances have changed provider-patient interactions in ambulatory care: (1) the replacement of virtual for in-person visits and (2) the COVID-19 pandemic. We studied the potential impact of each event on provider practice and patient adherence by comparing the frequency of the association of provider orders, and patient fulfillment of those orders, by visit mode and pandemic period, for incident neck or back pain (NBP) visits in ambulatory care. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente regions (Colorado, Georgia, and Mid-Atlantic States) from January 2017 to June 2021. Incident NBP visits were defined from ICD-10 coded as primary or first listed diagnoses on adult, family medicine, or urgent care visits separated by at least 180 days. Visit modes were classified as virtual or in-person. Periods were classified as prepandemic (before April 2020 or the beginning of the national emergency) or recovery (after June 2020). Percentages of provider orders for, and patient fulfillment of orders, were measured for 5 service classes and compared on: virtual versus in-person visits, and prepandemic versus recovery periods. Comparisons were balanced on patient case-mix using inverse probability of treatment weighting. RESULTS: Ancillary services in all 5 categories at each of the 3 Kaiser Permanente regions were substantially ordered less frequently on virtual compared with in-person visits in both the prepandemic and recovery periods (both P ≤ 0.001). Conditional on an order, patient fulfillment within 30 days was high (typically ≥70%) and not likely meaningfully different between visit modes or pandemic periods. CONCLUSIONS: Ancillary services for incident NBP visits were ordered less frequently during virtual than in-person visits in both prepandemic and recovery periods. Patient fulfillment of orders was high, and not significantly different by mode or period.

Did Access to Ambulatory Care Moderate the Associations Between Visit Mode and Ancillary Services Utilization Across the COVID-19 Pandemic Period?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances changed provider-patient interactions in primary care: the substitution of virtual (eg, video) for in-person visits and the COVID-19 pandemic. We studied whether access to care might affect patient fulfillment of ancillary services orders for ambulatory diagnosis and management of incident neck or back pain (NBP) and incident urinary tract infection (UTI) for virtual versus in-person visits. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente Regions to identify incident NBP and UTI visits from January 2016 through June 2021. Visit modes were classified as virtual (Internet-mediated synchronous chats, telephone visits, or video visits) or in-person. Periods were classified as prepandemic [before the beginning of the national emergency (April 2020)] or recovery (after June 2020). Percentages of patient fulfillment of ancillary services orders were measured for 5 service classes each for NBP and UTI. Differences in percentages of fulfillments were compared between modes within periods and between periods within the mode to assess the possible impact of 3 moderators: distance from residence to primary care clinic, high deductible health plan (HDHP) enrollment, and prior use of a mail-order pharmacy program. RESULTS: For diagnostic radiology, laboratory, and pharmacy services, percentages of fulfilled orders were generally >70-80%. Given an incident NBP or UTI visit, longer distance to the clinic and higher cost-sharing due to HDHP enrollment did not significantly suppress patients' fulfillment of ancillary services orders. Prior use of mail-order prescriptions significantly promoted medication order fulfillments on virtual NBP visits compared with in-person NBP visits in the prepandemic period (5.9% vs. 2.0%, P=0.01) and in the recovery period (5.2% vs. 1.6%, P=0.02). CONCLUSIONS: Distance to the clinic or HDHP enrollment had minimal impact on the fulfillment of diagnostic or prescribed medication services associated with incident NBP or UTI visits delivered virtually or in-person; however, prior use of mail-order pharmacy option promoted fulfillment of prescribed medication orders associated with NBP visits.

Development of a Common Data Model for a Multisite and Multiyear Study of Virtual Visit Implementation: A Case Study.

BACKGROUND/OBJECTIVE: In multisite studies, a common data model (CDM) standardizes dataset organization, variable definitions, and variable code structures and can support distributed data processing. We describe the development of a CDM for a study of virtual visit implementation in 3 Kaiser Permanente (KP) regions. METHODS: We conducted several scoping reviews to inform our study's CDM design: (1) virtual visit mode, implementation timing, and scope (targeted clinical conditions and departments); and (2) extant sources of electronic health record data to specify study measures. Our study covered the period from 2017 through June 2021. Integrity of the CDM was assessed by a chart review of random samples of virtual and in-person visits, overall and by specific conditions of interest (neck or back pain, urinary tract infection, major depression). RESULTS: The scoping reviews identified a need to address differences in virtual visit programs across the 3 KP regionsto harmonize measurement specifications for our research analyses. The final CDM contained patient-level, provider-level, and system-level measures on 7,476,604 person-years for KP members aged 19 years and above. Utilization included 2,966,112 virtual visits (synchronous chats, telephone visits, video visits) and 10,004,195 in-person visits. Chart review indicated the CDM correctly identified visit mode on>96% (n=444) of visits, and presenting diagnosis on >91% (n=482) of visits. CONCLUSIONS: Upfront design and implementation of CDMs may be resource intensive. Once implemented, CDMs, like the one we developed for our study, provide downstream programming and analytic efficiencies by harmonizing, in a consistent framework, otherwise idiosyncratic temporal and study site differences in source data.