Resolving the H I in damped Lyman α systems that power star formation.

Reservoirs of dense atomic gas (primarily hydrogen) contain approximately 90 per cent of the neutral gas at a redshift of 3, and contribute to between 2 and 3 per cent of the total baryons in the Universe1-4. These 'damped Lyman α systems'-so called because they absorb Lyman α photons within and from background sources-have been studied for decades, but only through absorption lines present in the spectra of background quasars and γ-ray bursts5-10. Such pencil beams do not constrain the physical extent of the systems. Here we report integral-field spectroscopy of a bright, gravitationally lensed galaxy at a redshift of 2.7 with two foreground damped Lyman α systems. These systems are greater than 238 kiloparsecs squared in extent, with column densities of neutral hydrogen varying by more than an order of magnitude on scales of less than 3 kiloparsecs. The mean column densities are between 1020.46 and 1020.84 centimetres squared and the total masses are greater than 5.5 × 108-1.4 × 109 times the mass of the Sun, showing that they contain the necessary fuel for the next generation of star formation, consistent with relatively massive, low-luminosity primeval galaxies at redshifts greater than 2.

A Network Theory Approach to Curriculum Design.

In this paper we hypothesize that education, especially at the scale of curriculum, should be treated as a complex system composed of different ideas and concepts which are inherently connected. Therefore, the task of a good teacher lies in elucidating these connections and helping students make their own connections. Such a pedagogy allows students to personalize learning and strive to be 'creative' and make meaning out of old ideas. The novel contribution of this work lies in the mathematical approach we undertake to verify our hypothesis. We take the example of a precalculus course curriculum to make our case. We treat textbooks as exemplars of a specific pedagogy and map several texts into networks of isolated (nodes) and interconnected concepts (edges) thereby permitting computations of metrics which have much relevance to the education theorists, teachers and all others involved in the field of education. We contend that network metrics such as average path length, clustering coefficient and degree distribution provide valuable insights to teachers and students about the kind of pedagogy which encourages good teaching and learning.

Safety and Efficacy of Oral Anticoagulants for Atrial Fibrillation in Patients After Bariatric Surgery.

Anticoagulation management is challenging in bariatric surgery patients, due to altered gastrointestinal anatomy and potentially reduced absorption. Few studies have evaluated clinical outcomes in this population. The objective of this study was to compare the efficacy and safety of oral anticoagulants in patients with and without a history of bariatric surgery. A retrospective, matched cohort study was conducted, utilizing data from the OptumLabs Data Warehouse. Patients ≥18 years old, with nonvalvular atrial fibrillation (NVAF), and treated with an oral anticoagulant between January 1, 2010 and December 31, 2018 were included. Outcomes were compared between bariatric and nonbariatric surgery patients. Secondary analysis compared warfarin to the direct oral anticoagulants (DOAC) in the bariatric cohort. The primary efficacy outcome was the rate of ischemic stroke and systemic embolism and the primary safety outcome was major bleeding. A total of 1,673 bariatric surgery and 155,619 nonbariatric surgery patients were identified. There was no significant difference in the rate of ischemic stroke or systemic embolism (0.83 vs 1.32 per 100 person years; Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.31 to 1.22; p = 0.17) or major bleeding (5.30 vs 4.87 per 100 person years; HR 1.05, 95% CI 0.80 to 1.37; p = 0.73) between bariatric and nonbariatric surgery patients. In bariatric surgery patients alone, efficacy and safety were similar with warfarin compared with the DOACs. Results of this study suggest that bariatric surgery patients are not at an increased thrombotic or bleeding risk when using oral anticoagulants for NVAF. DOACs may be a reasonable alternative to warfarin.

Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82-1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62-1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Using knowledge translation for quality improvement: an interprofessional education intervention to improve thromboprophylaxis among medical inpatients.

BACKGROUND: Low-molecular-weight heparin (LMWH) is an effective means of preventing venous thromboembolism (VTE) among medical inpatients. Compared with unfractionated heparin, LMWH is equivalent or superior in efficacy and risk of bleeding. Despite its advantages, LMWH is underused in VTE prophylaxis for general-medicine patients hospitalized at our institution. Thus, a quality improvement (QI) initiative was undertaken to increase LMWH use for VTE prophylaxis among medical patients hospitalized on resident teaching services. METHODS: A QI team was formed, consisting of resident and attending physicians with pharmacy leaders. A systems analysis was performed, which showed gaps in resident knowledge as the greatest barrier to LMWH use. A knowledge translation framework was used to improve prescribing practices. Several Plan-Do-Study-Act cycles were executed, including resident-of-resident and pharmacist-of-resident education with performance audit and feedback. RESULTS: Pharmacist-of-resident education elicited the largest improvement and was sustained through a recurring pharmacist-led, interprofessional educational session as part of the monthly hospital orientation for incoming residents. Data analysis showed a statistically significant increase in LMWH use among treatment-eligible hospitalized medical patients, from 12.1% to 69.2%, following intervention (P<0.001). Extrapolated over 1 year, this improvement conserved 9,490 injections and nearly 791 hours of nurse time. CONCLUSIONS: This QI project indicates that an interprofessional education intervention can lead to sustainable improvement in resident prescribing practices. This project also highlights the value of knowledge translation for the design of tailored interventions in QI initiatives.

Improving inpatient warfarin therapy safety using a pharmacist-managed protocol.

INTRODUCTION: Safe management of warfarin in the inpatient setting can be challenging. At the Mayo Clinic hospitals in Rochester, Minnesota, we set out to improve the safety of warfarin management among surgical and non-surgical inpatients. METHODS: A multidisciplinary team designed a pharmacist-managed warfarin protocol (PMWP) which designated warfarin dosing to inpatient pharmacists with guidance from computerised dosing algorithms. Ordering this protocol was ultimately designed as an 'opt out' practice. The primary improvement measure was frequency of international normalised ratio (INR) greater than 5; secondary measures included adoption rate of the protocol, a counterbalance INR metric (INR <1.7 three days after first inpatient warfarin dose), and complication rates, including bleeding and thrombosis events. An interrupted time series analysis was conducted to compare outcomes. RESULTS: Among over 50 000 inpatient warfarin recipients, the PMWP was adopted for the majority of both surgical and non-surgical inpatients during the study period (1 January 2005 to 31 December 2011). The primary improvement measure decreased from 5.6% to 3.4% for medical patients and from 5.2% to 2.4% for surgical patients during the preimplementation and postimplementation periods, respectively. The INR counterbalance measure did not change. Postoperative bleeding decreased from 13.5% to 11.1% among surgical patients, but bleeding was unchanged among medical patients. CONCLUSION: Our PMWP led to achievement of improved INR control for inpatient warfarin recipients and to less near-term bleeding among higher risk, surgical patients.

Going Beyond Administrative Data: Retrospective Evaluation of an Algorithm Using the Electronic Health Record to Help Identify Bleeding Events Among Hospitalized Medical Patients on Warfarin.

To reliably assess quality, a standardized electronic approach is needed to identify bleeding events. The study aims were the following: (1) clinically validate an electronic health record-based algorithm for bleeding and (2) assess interrater results to determine validity and reliability. Data were analyzed before and after implementation of a pharmacist-managed warfarin protocol. Bleeding was based on ≥2 of 3 criteria: (1) diagnosis indicating bleeding, (2) lab value decrease suggesting bleeding, and (3) blood product use. All suspected bleeds (234) and a sample (58) not meeting criteria were compared with clinical review. There were 234 bleeding cases identified electronically. Reviewer agreement was 78.2% (κ = 0.565). Algorithm sensitivity was 93.9% and positive predictive value 46.2%. Algorithm identification was least accurate for those with only 2 criteria but good for those with all criteria. This study supports using multiple electronic criteria to identify bleeding events. However, cases having exactly 2 criteria may require manual review for validation.

Mealtime Insulin Dosing by Carbohydrate Counting in Hospitalized Cardiology Patients: A Retrospective Cohort Study.

BACKGROUND: Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. MATERIALS AND METHODS: This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010-November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. RESULTS: Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P=0.04, adjusted P=0.12). There were no statistical differences between groups on Days 2-6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P=0.02), Day 6 (1.7% vs. 0%, P=0.01), and Day 7 (7.1% vs. 0%, P=0.008). No differences in postprandial hypoglycemia were seen. CONCLUSIONS: Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.

Assessment of the presence and quality of osteoporosis prevention education among at-risk internal medicine patients.

OBJECTIVE: Appropriate calcium and vitamin D intake for the prevention of osteoporosis represents an important component of osteoporosis prevention education (OPE). We sought to assess the presence and quality of OPE among osteoporotic and at-risk inpatients. DESIGN: Prospective chart review plus cross-sectional interview. SETTING: One academic tertiary referral medical center in Rochester, Minnesota. PARTICIPANTS: Adults admitted to an inpatient medicine service who were determined to be at risk for osteoporosis based on an investigator-developed screening tool or previously diagnosed with osteoporosis. Four hundred sixtyfour patients were screened, 192 patients were approached for participation, and 150 patients consented to be interviewed for the study. MAIN OUTCOME MEASURES: Source of OPE, rates of appropriate calcium intake and supplementation. RESULTS: OPE from a health care provider was reported by 31.3% of patients, with only one patient reporting education from a pharmacist. Self OPE and no OPE were received by 29.3% and 39.3% of patients, respectively. Appropriate overall calcium intake was found in 30.7% of patients, and only 21.3% of patients were taking an appropriate calcium salt. CONCLUSION: Patients with osteoporosis and risk factors for osteoporosis lack adequate education from health care providers regarding appropriate intake of dietary and supplemental calcium and vitamin D. A particular deficit was noted in pharmacist-provided education. Specific education targeting elemental calcium amounts, salt selection, and vitamin D intake should be provided to increase the presence of appropriate overall calcium consumption.

Risk factors for excessive anticoagulation among hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol.

STUDY OBJECTIVE: To identify specific risk factors for excessive anticoagulation, defined as an international normalized ratio (INR) higher than 5, in hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol. DESIGN: Retrospective nested case-control study. SETTING: Large academic tertiary care medical center. PATIENTS: Hospitalized nonsurgical patients 18 years or older who received at least one dose of warfarin according to the pharmacist-managed protocol from January 1, 2009, to January 31, 2012, were included. Patients who experienced an INR higher than 5 were designated as case patients; those who received warfarin for at least as many days as the case patients but who did not experience an INR more than 5 were deemed control patients. Controls were matched to cases in a 2:1 ratio by age, sex, INR goal, and type of warfarin therapy (new start or continuation). MEASUREMENTS AND MAIN RESULTS: A total of 87 case patients were matched to 174 controls. Ten different hypothesized risk factors were examined. Two variables, severity of illness score (odds ratio [OR] 4.89, p<0.001) and poor nutritional status (OR 4.27, p<0.001), demonstrated strong independent associations with risk of excessive anticoagulation. Administration of interacting drugs that highly potentiate warfarin's effect (OR 2.26, p=0.011) and concurrent diarrheal illness (OR 4.75, p<0.001) also displayed a statistically significant risk for excessive anticoagulation. CONCLUSION: Even in a highly standardized system for warfarin dosing by a pharmacist-managed protocol, higher disease severity and poor nutritional status placed hospitalized patients at greater risk of experiencing excessive anticoagulation. In addition, administration of interacting drugs that highly potentiate warfarin's effect or the occurrence of diarrheal illness may predict increased risk.

Detection of pristine gas two billion years after the Big Bang.

In the current cosmological model, only the three lightest elements were created in the first few minutes after the Big Bang; all other elements were produced later in stars. To date, however, heavy elements have been observed in all astrophysical environments. We report the detection of two gas clouds with no discernible elements heavier than hydrogen. These systems exhibit the lowest heavy-element abundance in the early universe, and thus are potential fuel for the most metal-poor halo stars. The detection of deuterium in one system at the level predicted by primordial nucleosynthesis provides a direct confirmation of the standard cosmological model. The composition of these clouds further implies that the transport of heavy elements from galaxies to their surroundings is highly inhomogeneous.

Extended Outcomes of Complex Coronary Disease in the Drug Eluting Stent Era.

BACKGROUND: Several randomized trials comparing bare-metal stents to Drug-Eluting Stents (DES) have demonstrated a significant reduction in Target Vessel Revascularization (TVR) and Target Lesion Revascularization (TLR) exists with the use of drug-eluting stents, without compromising survival. These conclusions are based on restricted inclusion criteria for patients and lesion. It is unknown if these results can be generalized to an unselected patient population and more complex disease. The objective of this study was to determine to what extent the availability of DES has impacted survival, TVR, and TLR in a large regional experience without the restriction of on-label indications. METHODS: Patients registered with the Northern New England Cardiovascular Disease Study Group's PCI registry with single vessel coronary disease undergoing a first PCI were sorted according to the Bare-Metal stent (BMS) era (2001 - 2002) or the Drug-Eluting stent (DES) era (2004 - 2005) based on the time period their first PCI took place. Totally, 6,093 BMS and 5,651 DES patients were identified. Outcomes of survival, TLR and TVR were measured after one year. RESULTS: After 1 year, survival was comparable, TLR was reduced by 4.9% (absolute) and TVR was reduced by 5.4% (absolute) in the DES era compared to the BMS era. The TLR/TVR differences remained significant after propensity matching in the DES era vs BMS era (Mortality: HR 1.00, 95% CI: 0.83 - 1.28; TLR: HR 0.40, 95% CI 0.32 - 0.46; TVR: HR 0.44, 95% CI 0.38 - 0.51). CONCLUSIONS: In large regional experience with a consecutive series of patients representing the contemporary practice of PCI, including both on and off label use, the frequent use of DES reduces the risk of TVR and TLR without compromising survival.

Multidisciplinary approach to inpatient medication reconciliation in an academic setting.

PURPOSE: The effectiveness of a multidisciplinary medication reconciliation process was studied in an inpatient family medicine unit of an academic hospital center. METHODS: In phase 1 of this two-phase study, nurses, pharmacists, and physicians used an admission medication reconciliation form to reconcile patients' home medications on admission. The form was then reviewed by the pharmacist on the unit and by the attending physician, who reconciled the discharge medication list. The discharge medication list was compared against the patient's home medications list, inpatient medication profile, and prescriptions documented in the electronic medical record to investigate any medication discrepancies. Pharmacists participating in the study documented and categorized medication discrepancies by the potential severity of the error. In phase 2, family medicine medical residents and staff were instructed to include reconciled admission and discharge medication lists in the hospital summary. RESULTS: A total of 102 patients formed the study sample. There was no significant difference between phase 1 and phase 2 patients in mean age, sex, and length of hospital stay. Totals of 432 and 367 admission medications required reconciliation during phase 1 and phase 2, respectively. The mean number of admission medication discrepancies decreased from 0.5 per patient in phase 1 to 0 per patient in phase 2. The mean number of discharge medication discrepancies decreased from 3.3 per patient in phase 1 to 1.8 per patient in phase 2. CONCLUSION: The mean number of medication discrepancies occurring during admission and discharge decreased after a multidisciplinary medication reconciliation process was implemented in an inpatient family medicine unit of an academic hospital center.

3D: a tool for medication discharge education.

BACKGROUND: At the time of transition from hospital to home, many patients are challenged by multi-drug regimens. The authors' standard patient education tool is a personalised Medication Discharge Worksheet (MDW) that includes a list of medications and administration times. Nonetheless, patient understanding, satisfaction, and safety remain suboptimal. Therefore, the authors designed a new tool: Durable Display at Discharge (3D). Unlike MDW, 3D features (1) space in which a tablet or pill is to be affixed and displayed, (2) trade name (if apt), (3) unit strength, (4) number (and/or fraction) of units to be taken, (5) purpose (indication), (6) comment/caution, (7) larger font, (8) card stock durability and (9) a reconciliation feature. METHODS: The authors conducted an exploratory, randomised trial (n = 138) to determine whether 3D, relative to MDW, improves patient satisfaction, improves patient understanding and reduces self-reported medication errors. Trained survey research personnel, blinded to hypotheses, interviewed patients by telephone 7-14 days after discharge. RESULTS: Both tools were similarly associated with high satisfaction and few self-reported errors. However, 3D subjects demonstrated greater understanding of their medications. CONCLUSIONS: Although both tools are associated with similarly high levels of patient satisfaction and low rates of self-reported medication error, 3D appears to promote patient understanding of the medications, and warrants further study.

Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study.

BACKGROUND: Two ethnically different, community-based samples of hypertensive adults were evaluated to determine the prevalence of dyslipidemia and how often dyslipidemia is drug-treated and controlled by such treatment. METHODS: We studied 1286 non-Hispanic black hypertensive subjects from Jackson and 1070 non-Hispanic white hypertensive subjects from Rochester who participated in the Genetic Epidemiology Network of Arteriopathy study. Subjects were categorized according to presence of coronary heart disease and risk factors for coronary heart disease. RESULTS: Prevalence of dyslipidemia was significantly greater among whites than blacks (women, 64.7% vs 49.5%; and men, 78.4% vs 56.7%; P<.001 for both) and among men than women (P