Higher OAK (Oral Anticoagulation Knowledge) score at baseline associated with better TTR (Time in Therapeutic Range) in patients taking warfarin.

A lack in patient knowledge of warfarin therapy is associated with poor adherence. This knowledge gap may result in a lower INR Time in Therapeutic Range (TTR). To investigate association between patient anticoagulation knowledge and warfarin control. Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a Blue Cross Blue Shield of Michigan sponsored consortium of six anticoagulation management services. Patients prescribed warfarin at two MAQI2 sites completed a voluntary Oral Anticoagulation Knowledge (OAK) questionnaire at warfarin initiation and 6-month follow-up. The results of 20 OAK questions and TTRs (excluding 1st month post-initiation) were compared using chi-square tests, t-tests and multivariate analysis adjusting for SAMe-TT2R2 and days on warfarin. Of 1836 surveys distributed at warfarin initiation, 481 (26.2%) patients completed the baseline questionnaire (within 1 month post-initiation): mean OAK score: 14.6 ± 3.4. Of those, 147 (30.6%) completed 6-month follow-up surveys (OAK: 12.7 ± 5.8). Patients with TTR ≥ 70% at baseline scored higher on OAK tests than patients with TTR < 70% in unadjusted analyses (15.1 ± 3.2 v. 14.2 ± 3.5, p = 0.003) and adjusted analysis (p = 0.020). There was no unadjusted or adjusted difference in OAK scores at 6-month follow-up between patients with TTR ≥ 70% and TTR < 70%. For patients who completed baseline and follow-up surveys, there was a decrease of 2.4 points in OAK score between baseline and 6-month follow up (p < 0.001). Higher baseline, but not follow-up, OAK score is associated with better warfarin control and average OAK scores decreased between baseline and follow-up. Further studies are needed to determine what type of patient education may improve patient knowledge retention and warfarin control.

Root Cause Analysis of Adverse Events in an Outpatient Anticoagulation Management Consortium.

BACKGROUND: A number of factors can lead to adverse events (AEs) in patients taking warfarin. Performing a root cause analysis (RCA) of serious AEs is one systematic way of determining the causes of these events. METHODS: Multidisciplinary teams were formed at Michigan Anticoagulation Quality Improvement Initiative (MAQI2) sites with organized anticoagulation management services (AMS). Medical records from patients who suffered serious AEs (major bleed, embolic stroke, venous thromboembolism) were reviewed, and AMS staff were interviewed to determine the root cause using the "5 Whys" technique. More than 600 patients had an AE and underwent screening by trained RNs. Of these, 79 required full review by a multidisciplinary panel. All potential contributing factors (comorbidities, concurrent medications, current protocols) were assessed to determine the main factor that caused the AE. RESULTS: Full RCA was completed in 79 cases. The main contributing factor was identified in 69/79 (87%) cases. Most identified AEs, 55/69 (80%), were due to patient-specific factors such as comorbidities. Patient-to-provider and provider-to-provider communication accounted for 16/69 (23%) of events and was the second most common cause. Other causes included protocol non-adherence and technology/equipment issues. After each detailed review, the multidisciplinary panel recommended system changes that addressed the primary cause. CONCLUSION: The majority of severe AEs for patients taking warfarin were related to nonmodifiable patient-related issues. The remaining AEs were primarily due to patient-to-provider and provider-to-provider communication issues. Methods for improving communication need to be addressed, and methods for more effective patient education should be investigated.

Early millet use in northern China.

It is generally understood that foxtail millet and broomcorn millet were initially domesticated in Northern China where they eventually became the dominant plant food crops. The rarity of older archaeological sites and archaeobotanical work in the region, however, renders both the origins of these plants and their processes of domestication poorly understood. Here we present ancient starch grain assemblages recovered from cultural deposits, including carbonized residues adhering to an early pottery sherd as well as grinding stone tools excavated from the sites of Nanzhuangtou (11.5-11.0 cal kyBP) and Donghulin (11.0-9.5 cal kyBP) in the North China Plain. Our data extend the record of millet use in China by nearly 1,000 y, and the record of foxtail millet in the region by at least two millennia. The patterning of starch residues within the samples allow for the formulation of the hypothesis that foxtail millets were cultivated for an extended period of two millennia, during which this crop plant appears to have been undergoing domestication. Future research in the region will help clarify the processes in place.

Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.

Background: Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants. Objectives: (1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability. Methods: Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews. Results: Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable. Conclusion: The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.

OUTER RETINOPATHY AND MICROANGIOPATHY IN ACUTE MYELOGENOUS LEUKEMIA.

PURPOSE: To describe a patient with acute myelogenous leukemia who presented with a recurrent, bilateral, outer retinopathy, before and after consolidative peripheral blood stem cell transplantation complicated by chronic graft-versus-host disease. METHODS: This is a retrospective review of records from a 23-year-old woman with acute myelogenous leukemia who underwent comprehensive ophthalmic evaluations for over a year including chromatic perimetry and multifocal electroretinograms, imaging with spectral domain optical coherence tomography, near-infrared and short-wavelength fundus reflectance and autofluorescence, fluorescein and optical coherence tomography angiography. RESULTS: The patient presented with recurrent, unilateral paracentral scotomas. There was localized loss of inner segment ellipsoid (EZ) and photoreceptor outer segment signals (IZ) in the pericentral retina of both eyes co-localizing with hyperreflective lesions on near-infrared reflectance. She subsequently lost vision (visual acuity = 20/200) in the right eye a year after consolidative peripheral blood stem cell transplantation complicated by steroid-resistant-chronic graft-versus-host disease. There was loss of the EZ and IZ signals corresponding to a dense central cone scotoma and multifocal electroretinograms depression. Near-infrared autofluorescence, fluorescein and optical coherence tomography angiography were within normal limits. Visual acuity (20/20) and retinal sensitivities improved with restoration of the EZ/IZ signals after oral prednisone and intravenous rituximab, but left a residual photoreceptor loss and paracentral scotoma. CONCLUSION: We propose that an immune-mediated microangiopathy may explain the protracted, recurrent course of primary photoreceptor abnormalities in our patient, which was further complicated by manifestations of chronic graft-versus-host disease following consolidative peripheral blood stem cell transplantation. Outer retinal findings previously documented in leukemia may be explained by a similar mechanism.

Quasi-experimental, Nonrandomized Initiative to Minimize Sleep Disruptions among Hospitalized Children.

Hospitalized children experience frequent sleep disruptions. We aimed to reduce caregiver-reported sleep disruptions of children hospitalized on the pediatric hospital medicine service by 10% over 12 months. Methods: In family surveys, caregivers cited overnight vital signs (VS) as a primary contributor to sleep disruption. We created a new VS frequency order of "every 4 hours (unless asleep between 2300 and 0500)" as well as a patient list column in the electronic health record indicating patients with this active VS order. The outcome measure was caregiver-reported sleep disruptions. The process measure was adherence to the new VS frequency. The balancing measure was rapid responses called on patients with the new VS frequency. Results: Physician teams ordered the new VS frequency for 11% (1,633/14,772) of patient nights on the pediatric hospital medicine service. Recorded VS between 2300 and 0500 was 89% (1,447/1,633) of patient nights with the new frequency ordered compared to 91% (11,895/13,139) of patient nights without the new frequency ordered (P = 0.01). By contrast, recorded blood pressure between 2300 and 0500 was only 36% (588/1,633) of patient nights with the new frequency but 87% (11,478/13,139) of patient nights without the new frequency (P < 0.001). Overall, caregivers reported sleep disruptions on 24% (99/419) of reported nights preintervention, which decreased to 8% (195/2,313) postintervention (P < 0.001). Importantly, there were no adverse safety issues related to this initiative. Conclusion: This study safely implemented a new VS frequency with reduced overnight blood pressure readings and caregiver-reported sleep disruptions.

Early maize agriculture and interzonal interaction in southern Peru.

Over the past decade, increasing attention to the recovery and identification of plant microfossil remains from archaeological sites located in lowland South America has significantly increased knowledge of pre-Columbian plant domestication and crop plant dispersals in tropical forests and other regions. Along the Andean mountain chain, however, the chronology and trajectory of plant domestication are still poorly understood for both important indigenous staple crops such as the potato (Solanum sp.) and others exogenous to the region, for example, maize (Zea mays). Here we report the analyses of plant microremains from a late preceramic house (3,431 +/- 45 to 3,745 +/- 65 14C bp or approximately 3,600 to 4,000 calibrated years bp) in the highland southern Peruvian site of Waynuna. Our results extend the record of maize by at least a millennium in the southern Andes, show on-site processing of maize into flour, provide direct evidence for the deliberate movement of plant foods by humans from the tropical forest to the highlands, and confirm the potential of plant microfossil analysis in understanding ancient plant use and migration in this region.

Development of a multicomponent implementation strategy to reduce upper gastrointestinal bleeding risk in patients using warfarin and antiplatelet therapy, and protocol for a pragmatic multilevel randomized factorial pilot implementation trial.

BACKGROUND: The concomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS), and the design of a pilot pragmatic implementation trial. METHODS: A participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: the nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review. DISCUSSION: This pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase the use of best practices for upper GI bleeding risk reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085405 . Registered on October 19, 2021-retrospectively registered.

Morphological changes in starch grains after dehusking and grinding with stone tools.

Research on the manufacture, use, and use-wear of grinding stones (including slabs and mullers) can provide a wealth of information on ancient subsistence strategy and plant food utilization. Ancient residues extracted from stone tools frequently exhibit damage from processing methods, and modern experiments can replicate these morphological changes so that they can be better understood. Here, experiments have been undertaken to dehusk and grind grass grain using stone artifacts. To replicate ancient activities in northern China, we used modern stone tools to dehusk and grind twelve cultivars of foxtail millet (Setaria italica), two cultivars of broomcorn millet (Panicum miliaceum) and three varieties of green bristlegrass (Setaira viridis). The residues from both used and unused facets of the stone tools were then extracted, and the starch grains studied for morphological features and changes from the native states. The results show that (1) Dehusking did not significantly change the size and morphology of millet starch grains; (2) After grinding, the size of millet starch grains increases up to 1.2 times larger than native grains, and a quarter of the ground millet starch grains bore surface damage and also exhibited distortion of the extinction cross. This indicator will be of significance in improving the application of starch grains to research in the functional inference of grinding stone tools, but we are unable to yet distinguish dehusked forms from native.

Critical role of climate change in plant selection and millet domestication in North China.

While North China is one of the earliest independent centers for cereal domestication in the world, the earliest stages of the long process of agricultural origins remain unclear. While only millets were eventually domesticated in early sedentary societies there, recent archaeobotanical evidence reported here indicates that grasses from the Paniceae (including millets) and Triticeae tribes were exploited together by foraging groups from the Last Glacial Maximum to the mid-Holocene. Here we explore how and why millets were selected for domestication while Triticeae were abandoned. We document the different exploitation and cultivation trajectories of the two tribes employing ancient starch data derived from nine archaeological sites dating from 25,000 to 5500 cal BP (LGM through mid-Holocene) in North China. With this diachronic overview, we can place the trajectories into the context of paleoclimatic reconstructions for this period. Entering the Holocene, climatic changes increased the yield stability, abundance, and availability of the wild progenitors of millets, with growing conditions increasingly favoring millets while becoming more unfavorable for grasses of the Triticeae tribe. We thus hypothesize that climate change played a critical role in the selection of millet species for domestication in North China, with early domestication evidenced by 8700 cal BP.

Multiple indicators of rice remains and the process of rice domestication: A case study in the lower Yangtze River region, China.

The process of rice domestication has been studied for decades based on changing morphological characteristics in assemblages of both macroremains, such as charred seeds and spikelet bases, and microremains, such as phytoliths, esp. bulliform and double-peaked phytoliths. The applicability of these indicators in determining if a specific assemblage is wild or domesticated, however, is rarely discussed. To understand the significance of these indicators in the determination of domestication, we collected 38 archaeological samples from eight Neolithic sites, dating from 10-2ka BP, in the lower Yangtze River region to analyze and compare the changes of these different indicators over eight thousand years. The data demonstrate that the comprehensive analysis of multiple indicators may be the best method to study the process of rice domestication developed thus far. An assemblage of rice remains can be identified as domesticated forms if they meet the following criteria simultaneously: 1) the proportion of domesticated-type bulliform phytoliths is more than 73%; and 2) the proportion of domesticated-type rice spikelet bases is higher than 75%. Furthermore, we found that each indicator tends to change steadily and gradually over time, and each stabilized at a different time, suggesting that the characteristics of domesticated rice developed slowly and successively. Changes of multiple indicators during the period between 10,000-2,000 yr BP indicate that the process of rice domestication in the lower Yangtze River region lasted as long as ca. 6,000 years during the Neolithic, and can be divided into three stages with the turning points in the middle Hemudu-late Majiabang culture (6,500-5,800yr BP) and the late Liangzhu culture (4,600-4,300yr BP).

Barnyard grasses were processed with rice around 10000 years ago.

Rice (Oryza sativa) is regarded as the only grass that was selected for cultivation and eventual domestication in the Yangtze basin of China. Although both macro-fossils and micro-fossils of rice have been recovered from the Early Neolithic site of Shangshan, dating to more than 10,000 years before present (BP), we report evidence of phytolith and starch microfossils taken from stone tools, both for grinding and cutting, and cultural layers, that indicating barnyard grass (Echinochloa spp.) was a major subsistence resource, alongside smaller quantities of acorn starches (Lithocarpus/Quercus sensu lato) and water chestnuts (Trapa). This evidence suggests that early managed wetland environments were initially harvested for multiple grain species including barnyard grasses as well as rice, and indicate that the emergence of rice as the favoured cultivated grass and ultimately the key domesticate of the Yangtze basin was a protracted process.

Impact of empire expansion on household diet: the Inka in Northern Chile's Atacama Desert.

The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored. Using the analysis of starch residues recovered from coprolites, here we evaluate the dietary adaptations of indigenous farmers in northern Chile's Atacama Desert during the time that the Inka Empire incorporated these communities into their economic system. This system has been described as "complementarity" because it involves interaction and trade in goods produced at different Andean elevations. We find that as local farming societies adapted to this new asymmetric system, a portion of their labor had to be given up to the Inka elite through a corvée tax system for maize production. In return, the Inka system of complementarity introduced previously rare foods from the Andean highlands into local economies. These changes caused a disruption of traditional communities as they instituted a state-level economic system on local farmers. Combined with previously published infection information for the same populations under Inka rule, the data suggest that there may have been a dual health impact from disruption of nutrition and introduction of crowd disease.

Precolumbian use of chili peppers in the Valley of Oaxaca, Mexico.

Excavations at Guilá Naquitz and Silvia's Cave, two dry rockshelters near Mitla, Oaxaca, Mexico, yielded the remains of 122 chili peppers dating to the period A.D. 600-1521. The chilies can be assigned to at least 10 cultivars, all belonging to the species Capsicum annuum or Capsicum frutescens. The specimens are well enough preserved to permit an evaluation of the criteria used to separate wild and domestic chilies and to distinguish among cultivated races. In addition, they provide the opportunity to assess the reliability of starch grains for documenting the presence of chilies in archaeological sites where no macrobotanical remains are preserved.

Starch fossils and the domestication and dispersal of chili peppers (Capsicum spp. L.) in the Americas.

Chili peppers (Capsicum spp.) are widely cultivated food plants that arose in the Americas and are now incorporated into cuisines worldwide. Here, we report a genus-specific starch morphotype that provides a means to identify chili peppers from archaeological contexts and trace both their domestication and dispersal. These starch microfossils have been found at seven sites dating from 6000 years before present to European contact and ranging from the Bahamas to southern Peru. The starch grain assemblages demonstrate that maize and chilies occurred together as an ancient and widespread Neotropical plant food complex that predates pottery in some regions.

Starch analyses reveal multiple functions of quartz "manioc" grater flakes from the Orinoco basin, Venezuela

El acuerdo general existente entre arquólogos que la yuca amarga era el cultivo básico en los sistemas agrícolas prehispánicos de las tierras bajas de Sudamérica se basa en evidencias indirectas aportadas por arreglos cerámicos y líticos arqueológicos en lugar de restos preservados de la yuca misma. Se diseñaron estudios de dientes microlíticos de ralladores del sitio Pozo Azul Norte-I en la cuenca del Orinoco Medio para recuperar restos de almidón de yuca amarga y evaluar la confiabilidad de la presunción que esos artefactos son un indicador arqueológico seguro del uso de la yuca amarga. Los datos indican que los artefactos para "YUCA" nos son necesariamente indicativos del uso de la yuca por los pobladores prehispánicos del Orinoco Medio, y que los datos arqueológicos son un indicador más confiable de las actividades prehispánicas de subsistencia que los análogos etnográficos modernos