Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Surgical Management of Tophaceous Gout in the Upper Limb.

PURPOSE: Gouty tophi are a clinical manifestation of hyperuricemia in advanced stages. They can produce pain, functional limitation, and severe deformities. Patients with severe symptoms require short-term symptomatic solutions that standard medical management is not able to provide. The objective of this study was to present the results obtained with the surgical management of tophaceous gout in the upper limb, as well as present a detailed characterization of the disease in the upper limb. METHODS: Databases of the hand surgery service of a quaternary care hospital were reviewed to identify patients aged >18 years old undergoing tophi resection in the upper limbs between 2014 and 2020. Medical history records were reviewed retrospectively, and the relevant data were extracted to establish demographic profile, clinical presentation, anatomic distribution, postoperative outcomes, and additional procedures required. RESULTS: The most frequent symptom was pain (83%), followed by limited range of motion (56%), deformity (50%), and daily living/occupational activity limitation (28%). The main indications for surgical management were the presence of deformity, pain, and/or limited range of motion. The most frequently affected anatomic sites were the metacarpophalangeal joints, followed by the elbows, proximal interphalangeal joints, and proximal phalanges. The postoperative complication rate was 28%. The most common complications were operative site infections and wound dehiscence. Decreased pain was associated with surgical resection. Additional procedures, such as extensor tenorrhaphy and local flaps, were required in 47.2% of patients. CONCLUSION: Surgical resection of tophi can decrease pain. Although surgery is associated with a high rate of complications, most are minor. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Impacts of the Molecular Education and Research Consortium in Undergraduate Computational Chemistry on the Careers of Women in Computational Chemistry.

The Molecular Education and Research Consortium in Undergraduate Computational Chemistry (MERCURY) has supported a diverse group of faculty and students for over 20 years by providing computational resources as well as networking opportunities and professional support. The consortium comprises 38 faculty (42% women) at 34 different institutions, who have trained nearly 900 undergraduate students, more than two-thirds of whom identify as women and one-quarter identify as students of color. MERCURY provides a model for the support necessary for faculty to achieve professional advancement and career satisfaction. The range of experiences and expertise of the consortium members provides excellent networking opportunities that allow MERCURY faculty to support each other's teaching, research, and service needs, including generating meaningful scientific advancements and outcomes with undergraduate researchers as well as being leaders at the departmental, institutional, and national levels. While all MERCURY faculty benefit from these supports, the disproportionate number of women in the consortium, relative to their representation in computational sciences generally, produces a sizable impact on advancing women in the computational sciences. In this report, the women of MERCURY share how the consortium has benefited their careers and the careers of their students.

Safety and Revisit Related to Discharge the Sixty-one Spanish Emergency Department Medical Centers Without Hospitalization in Patients with COVID-19 Pneumonia. A Prospective Cohort Study UMC-Pneumonia COVID-19

ABSTRACT Background: Information is needed on the safety and efficacy of direct discharge from the emergency department (ED) of patients with COVID-19 pneumonia. Objectives: The objectives of the study were to study the variables associated with discharge from the ED in patients presenting with COVID-19 pneumonia, and study ED revisits related to COVID-19 at 30 days (EDR30d). Methods: Multicenter study of the SIESTA cohort including 1198 randomly selected COVID patients in 61 EDs of Spanish medical centers from March 1, 2020, to April 30, 2020. We collected baseline and related characteristics of the acute episode and calculated the adjusted odds ratios (aOR) for ED discharge. In addition, we analyzed the variables related to EDR30d in discharged patients. Results: We analyzed 859 patients presenting with COVID-19 pneumonia, 84 (9.8%) of whom were discharged from the ED. The variables independently associated with discharge were being a woman (aOR 1.890; 95%CI 1.176-3.037), age < 60 years (aOR 2.324; 95%CI 1.353-3.990), and lymphocyte count > 1200/mm3 (aOR 4.667; 95%CI 1.045-20.839). The EDR30d of the ED discharged group was 40.0%, being lower in women (aOR 0.368; 95%CI 0.142-0.953). A total of 130 hospitalized patients died (16.8%) as did two in the group discharged from the ED (2.4%) (OR 0.121; 95%CI 0.029-0.498). Conclusion: Discharge from the ED in patients with COVID-19 pneumonia was infrequent and was associated with few variables of the episode. The EDR30d was high, albeit with a low mortality.

Safety and Revisit Related to Discharge the Sixty-one Spanish Emergency Department Medical Centers Without Hospitalization in Patients with COVID-19 Pneumonia. A Prospective Cohort Study UMC-Pneumonia COVID-19.

BACKGROUND: Information is needed on the safety and efficacy of direct discharge from the emergency department (ED) of patients with COVID-19 pneumonia. OBJECTIVES: The objectives of the study were to study the variables associated with discharge from the ED in patients presenting with COVID-19 pneumonia, and study ED revisits related to COVID-19 at 30 days (EDR30d). METHODS: Multicenter study of the SIESTA cohort including 1198 randomly selected COVID patients in 61 EDs of Spanish medical centers from March 1, 2020, to April 30, 2020. We collected baseline and related characteristics of the acute episode and calculated the adjusted odds ratios (aOR) for ED discharge. In addition, we analyzed the variables related to EDR30d in discharged patients. RESULTS: We analyzed 859 patients presenting with COVID-19 pneumonia, 84 (9.8%) of whom weredischarged from the ED. The variables independently associated with discharge were being a woman (aOR 1.890; 95%CI 1.176 3.037), age < 60 years (aOR 2.324; 95%CI 1.353-3.990), and lymphocyte count > 1200/mm3 (aOR 4.667; 95%CI 1.045-20.839). The EDR30d of the ED discharged group was 40.0%, being lower in women (aOR 0.368; 95%CI 0.142-0.953). A totalof 130 hospitalized patients died (16.8%) as did two in the group discharged from the ED (2.4%) (OR 0.121; 95%CI 0.029-0.498). CONCLUSION: Discharge from the ED in patients with COVID-19 pneumonia was infrequent and was associated with few variables of the episode. The EDR30d was high, albeit with a low mortality.

Alcoholic Liver Disease Among Patients with Wernicke Encephalopathy: A Multicenter Observational Study.

BACKGROUND: data regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE. AIMS: to describe the frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD. METHODS: we conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed. RESULTS: 434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio [OR]=4.6 Confidence interval [CI]95% 1.1-18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1-21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8-59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030). CONCLUSION: the association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.

Graph analysis of proton conduction pathways in scandium-doped barium zirconate.

Understanding the relationship between the acceptor dopant size and proton conductivity in barium zirconate, BaZrO3, is important for maximizing efficiency in this promising fuel cell material. While proton conduction pathways with larger YZr ' and smaller AlZr ' defects have been explored, proton pathways with ScZr ', a defect of comparable size to the replaced ion, have not been investigated using centrality measures, periodic pathway searches, and kinetic Monte Carlo (KMC). Centrality measures in BaSc0.125Zr0.875O3 highlight a trapping region by ScZr ' and scattered high centrality regions on undoped planes. Connected long-range high centrality regions are found mainly in undoped planes for BaAl0.125Zr0.875O3 and in the dopant planes for BaY0.125Zr0.875O3. The best long-range proton conduction periodic pathways in AlZr ' and ScZr ' systems travel between dopant planes, while those for yttrium-doped BaZrO3 remained on dopant planes. KMC trajectories at 1000 K show long-range proton conduction barriers of 0.86 eV, 0.52 eV, and 0.25 eV for AlZr ', ScZr ', and YZr ' systems, respectively. Long-range periodic conduction highway limiting barrier averages correlate well with the connectivity of the most central regions in each system but ignore diffusion around the dopant and through other high centrality regions. BaSc0.125Zr0.875O3 shows an intermediate overall conduction barrier limited by trapping, which earlier experiments and simulations suggest that it can be mitigated with increased oxygen vacancy concentration.

Local Distortions and Dynamics in Hydrated Y-Doped BaZrO3.

Y-doped BaZrO3 is a promising proton conductor for intermediate temperature solid oxide fuel cells. In this work, a combination of static DFT calculations and DFT based molecular dynamics (DFT-MD) was used to study proton conduction in this material. Geometry optimizations of 100 structures with a 12.5% dopant concentration allowed us to identify a clear correlation between the bending of the metal-oxygen-metal angle and the energies of the simulated cells. Depending on the type of bending, two configurations, designated as inward bending and outward bending, were defined. The results demonstrate that a larger bending decreases the energy and that the lowest energies are observed for structures combining inward bending with protons being close to the dopant atoms. These lowest energy structures are the ones with the strongest hydrogen bonds. DFT-MD simulations in cells with different yttrium distributions provide complementary microscopic information on proton diffusion as they capture the dynamic distortions of the lattice caused by thermal motion. A careful analysis of the proton jumps between different environments confirmed that the inward and outward bending states are relevant for the understanding of proton diffusion. Indeed, intra-octahedral jumps were shown to only occur starting from an outward configuration while the inward configuration seems to favor rotations around the oxygen. On average, in the DFT-MD simulations, the hydrogen bond lengths are shorter for the outward configuration which facilitates the intra-octahedral jumps. Diffusion coefficients and activation energies were also determined and compared to previous theoretical and experimental data, showing a good agreement with previous data measuring local proton motion.

The CRAS-EAHFE study: Characteristics and prognosis of acute heart failure episodes with cardiorenal-anaemia syndrome at the emergency department.

BACKGROUND: The coexistence of other comorbidities confers poor outcomes in patients with acute heart failure. Our aim was to determine the characteristics of patients with acute heart failure and cardiorenal anaemia syndrome and the relationship between renal dysfunction and anaemia, alone or combined as cardiorenal anaemia syndrome, on short-term outcomes. METHODS: We analysed the Epidemiology of Acute Heart Failure in Emergency Departments registry (cohort of patients with acute heart failure in Spanish emergency departments). Renal dysfunction was defined by an estimated glomerular filtration rate <60 ml/min/m2, anaemia by haemoglobin values <12/<13 g/dl in women/men, and cardiorenal anaemia syndrome as the presence of both. Comparisons were made according to cardiorenal-anaemia syndrome positive (CRAS+) with respect to the rest of patients (CRAS-) and according the presence of renal dysfunction (RD+) and anaemia (A+), (alone, RD+/A-, RD-/A+) or in combination (RD+/A+; i.e. CRAS+) with respect to patients without renal dysfunction and anaemia (RD-/A-). The primary outcome was 30-day mortality, and the secondary outcomes were need for admission, prolonged hospitalisation (>10 days), in-hospital mortality during the index event, and reconsultation and the combination of 30-day post-discharge reconsultation/death. These short-term outcomes were compared and adjusted for differences among groups. RESULTS: Of the 13,307 patients analysed, CRAS+ (36.4%) was associated with older age, multiple comorbidities, chronic use of loop diuretics, oedemas and hypotension. The 30-day mortality in CRAS+ was greater than in CRAS- (hazard ratio = 1.46, 95% confidence interval = 1.26-1.68) and RD-/A- (hazard ratio = 1.83, 95% confidence interval = 1.46-2.28) control groups. The mortality level was also higher in RD+/A- (hazard ratio = 1.40, 95% confidence interval = 1.10-1.78) and higher, but not statistically significant, in RD-/A+ (hazard ratio = 1.28, 95% confidence interval = 0.99-1.63) with respect to RD-/A-. All of the secondary outcomes, when related to CRAS- and RD-/A- control groups, were worse for CRAS+ and to a lesser extent, RD+/A-, being more rarely observed in RD-/A+. CONCLUSIONS: Cardiorenal anaemia syndrome in acute heart failure is related to greater mortality and worse short-term outcomes, and the impact of renal dysfunction and anaemia seems to be additive.

URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia.

BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid (UA) reabsorption in the proximal tubule, is caused by mutations in SLC22A12 or SLC2A9. Most mutations have been identified in Japanese patients, and only a few have been detected in Europeans. METHODS: We report clinical, biochemical and genetics findings of fourteen Spanish patients, six Caucasians and eight of Roma ethnia, diagnosed with idiopathic RHUC. Two of the patients presented exercise-induced acute renal failure and another one had several episodes of nephrolithiasis and four of them had progressive deterioration of renal function, while the rest were asymptomatic. RESULTS: Molecular analysis revealed SLC22A12 mutations in ten of the patients, and SLC2A9 mutations in the other four. A new heterozygous SLC22A12 missense mutation, c.1427C>A (p.A476D), was identified in two affected members of the same family. The rest of the patients presented homozygous, heterozygous or compound heterozygous mutations that have been previously identified in patients with RHUC; SLC22A12 p.T467M and p.L415_G417del, and SLC2A9 p.T125M. Expression studies in Xenopus oocytes revealed that c.1427C>A reduced UA transport but did not alter the location of URAT1 protein on the plasma membrane. CONCLUSIONS: The biochemical and clinical features of our patients together with the genetic analysis results confirmed the diagnosis of RHUC. This is the first report describing SLC22A12 and SLC2A9 mutations in Spanish patients.

Fossil record of Ephedra in the Lower Cretaceous (Aptian), Argentina.

Fossil plants from the Lower Cretaceous (upper Aptian) of the La Cantera Formation, Argentina, are described. The fossils studied represent a leafy shooting system with several orders of articulated and striated axes and attached leaves with unequivocal ephedroid affinity. We also found associated remains of ovulate cones with four whorls of sterile bracts, which contain two female reproductive units (FRU). Ovulate cone characters fit well within the genus Ephedra. Special characters in the ovulate cones including an outer seed envelope with two types of trichomes, allowed us to consider our remains as a new Ephedra species. Abundant dispersed ephedroid pollen obtained from the macrofossil-bearing strata also confirms the abundance of Ephedraceae in the basin. The co-occurrence of abundant fossil of Ephedra (adapted to dry habitats) associated with thermophilic cheirolepideacean conifer pollen (Classopollis) in the unit would suggest marked seasonality at the locality during the Early Cretaceous. Furthermore, the floristic association is linked to dry sensitive rocks in the entire section. The macro- and microflora from San Luis Basin are similar in composition to several Early Cretaceous floras from the Northern Gondwana floristic province, but it may represent one of the southernmost records of an arid biome in South America.

Vasorelaxant Effect of a Baccharis trimera Infusion on Precontracted Rat Aortic Rings.

Baccharis trimera (Less.) DC is a South American plant that in folk medicine is considered to produce reduction in blood pressure. One aspect of this putative effect is the vasorelaxation. The aim of this work was to evaluate the ability of a B. trimera extract to relax rat aortic rings precontracted with noradrenaline. As the infusion is the usual way of intake of this plant, an infusion of B. trimera was prepared using 100 g of the plant (leaves) boiled in water, frozen and lyophilized. Working solutions were prepared using different concentrations of the dried extract diluted in Krebs Henseleit solution. It was proved that the infusion relaxed the aortic rings in a dose dependent manner 100 minutes after adding the exract to the bath. Considering as 100% the maximum contraction achieved with noradrenaline, a relaxation of 101.1 ± 2.3% was observed with the highest dose of the infusion used in these experiments (0.32 mg/mL). While in control rings relaxation was 12.9 ± 2.4%. In aortic rings denuded from endothelium the percentage of vasoralaxation did not show statistically significant differences when compared to intact rings. These data support the hypothesis of a vasorelaxant effect of this plant and constitutes the first approach to the scientific basis of a potential antihypertensive effect.

Centrality measures highlight proton traps and access points to proton highways in kinetic Monte Carlo trajectories.

A centrality measure based on the time of first returns rather than the number of steps is developed and applied to finding proton traps and access points to proton highways in the doped perovskite oxides: AZr(0.875)D(0.125)O3, where A is Ba or Sr and the dopant D is Y or Al. The high centrality region near the dopant is wider in the SrZrO3 systems than the BaZrO3 systems. In the aluminum-doped systems, a region of intermediate centrality (secondary region) is found in a plane away from the dopant. Kinetic Monte Carlo (kMC) trajectories show that this secondary region is an entry to fast conduction planes in the aluminum-doped systems in contrast to the highest centrality area near the dopant trap. The yttrium-doped systems do not show this secondary region because the fast conduction routes are in the same plane as the dopant and hence already in the high centrality trapped area. This centrality measure complements kMC by highlighting key areas in trajectories. The limiting activation barriers found via kMC are in very good agreement with experiments and related to the barriers to escape dopant traps.

Continuation rate of combined hormonal contraception: a prospective multicenter study.

BACKGROUND: Data from clinical trials regarding continuation of use and contraceptive efficacy do not always apply to the general public. Therefore, a study among typical users was conducted to assess the continuation rate at the end of 12 cycles of combined hormonal contraceptive methods, reasons for discontinuation, and the Pearl index. METHODS: Prospective, observational, and multicenter study of 3443 women aged 18 to 49 years starting one of the three combined hormonal contraception methods available in Spain (the vaginal ring, the contraceptive pill, and the transdermal skin patch). RESULTS: The study population (intention-to-treat analysis) included 3443 women, of whom 45.4% were included in the vaginal ring group, 42.6% the pill group, and 12.1% the skin patch group. The continuation rate at 12 cycles was 45.9% for the pill, 42.3% for the vaginal ring, and 26.0% for the skin patch. The Pearl index was 0.61 (95% confidence interval [CI] 0-1.2) for the pill, 0.61 (95% CI 0-1.1) for the vaginal ring, and 2.34 (95% CI 0.3-9) for the skin patch (p<0.001). CONCLUSION: At 12 cycles, the vaginal ring and the pill showed similar continuation rates and effectiveness, which were significantly higher than the skin patch.

The effect of dopant at the Zr site on the proton conduction pathways of SrZrO3: an orthorhombic perovskite.

Doping orthorhombic SrZrO(3) at 12.5% of the Zr sites with Al(3+) leads to a local squaring of the lattice, while doping with larger Y(3+) increases local octahedral distortions. Proton activation energy barriers and transition state theory prefactors are calculated. The wide range of intra-, inter-, and rotational barriers suggest that a comprehensive pathway analysis is needed to find the limiting conduction barriers. Simple seven to ten step periodic pathways leading to system wide conduction are enumerated using vertex coding. At 900-1300 K, the average limiting barriers to long range conduction are 0.6 and 0.4 eV in Al/SrZrO(3) and Y/SrZrO(3), respectively, in reasonable agreement with the experiment. Path analysis gives the added insight that conduction pathways in Al/SrZrO(3) avoid doped regions, while conduction pathways in Y/SrZrO(3) traverse them.

The effect of yttrium dopant on the proton conduction pathways of BaZrO3, a cubic perovskite.

When BaZrO(3) is doped with Y in 12.5% of Zr sites, density functional theory with the PBE functional predicts octahedral distortions within a cubic phase yielding a greater variety of proton binding sites than undoped BaZrO(3). Proton binding sites, transition states, and normal modes are found and used to calculate transition state theory rate constants. The binding sites are used to represent vertices in a graph. The rate constants connecting binding sites are used to provide weights for graph edges. Vertex and color coding are used to find proton conduction pathways in BaZr(0.875)Y(0.125)O(3). Many similarly probable proton conduction pathways which can be periodically replicated to yield long range proton conduction are found. The average limiting barriers at 600 K for seven step and eight step periodic pathways are 0.29 and 0.30 eV, respectively. Inclusion of a lattice reorganization barrier raises these to 0.42 and 0.33 eV, respectively. The majority of the seven step pathways have an interoctahedral rate limiting step while the majority of the eight step pathways have an intraoctahedral rate limiting step. While the average limiting barrier of the seven step periodic pathway including a lattice reorganization barrier is closer to experiment, how to appropriately weight different length periodic pathways is not clear. Likely, conduction is influenced by combinations of different length pathways. Vertex and color coding provide useful ways of finding the wide variety of long range proton conduction pathways that contribute to long range proton conduction. They complement more traditional serial methods such as molecular dynamics and kinetic Monte Carlo.

Profile of Puerto Rican HIV/AIDS patients with early and non-early initiation of injection drug use.

BACKGROUND: Early initiation of injection drug use (IDU) increases the risk of HIV infection. METHODS: We compare the sociodemographic, psychosocial, and clinical profiles of HIV-positive IDU patients according to the age at which IDU was initiated. This is a cross-sectional study of 1308 patients seen from 1992 through 2005. We compared the profile of patients with early (age < 13 years) vs non-early (age > 13 years) initiation of IDU. The Fisher and chi2 differences in proportions were performed to assess difference among study groups with earlier IDU. The Mantel-Haenszel test was used to calculate the odds ratio. The Kaplan-Meier and log rank tests were used to assess the median survival. Differences were considered significant at alpha = .05. RESULTS: Early initiation of IDU was reported in 11% of our sample. The early initiation group was more likely to smoke tobacco, use alcohol, attempt suicide, have a history of incarceration, have economic problems, and have episodes of anxiety, confusion, depression, excitation, impulsivity, and violence (P < .05). The general survival time of patients was 36.9 months (95% confidence interval 31.9-42.0). A higher prevalence of candidial esophagitis and Pneumocystis jirovecii pneumonia and a lower prevalence of hepatitis C virus coinfection were seen in the early initiation group (P < .05). No differences in mortality, use of antiretroviral therapy, or CD4 T-cell count were seen. CONCLUSIONS: Differences in terms of lifestyle, stress factors, and history of psychological events were seen in the group of patients with early initiation of IDU seen in our facilities. Differences in the clinical scenario were documented.