A robust time-delay selection criterion applied to convergent cross mapping.

This work presents a heuristic for the selection of a time delay based on optimizing the global maximum of mutual information in orthonormal coordinates for embedding a dynamical system. This criterion is demonstrated to be more robust compared to methods that utilize a local minimum, as the global maximum is guaranteed to exist in the proposed coordinate system for any dynamical system. By contrast, methods using local minima can be ill-posed as a local minimum can be difficult to identify in the presence of noise or may simply not exist. The performance of the global maximum and local minimum methods are compared in the context of causality detection using convergent cross mapping using both a noisy Lorenz system and experimental data from an oscillating plasma source. The proposed heuristic for time lag selection is shown to be more consistent in the presence of noise and closer to an optimal uniform time lag selection.

Risk of ischemic stroke associated with direct oral anticoagulants discontinuation on patients with non-valvular atrial fibrillation.

INTRODUCTION: Although direct oral anticoagulants' (DOACs) prescriptions have experienced immense growth in the last decade, the proportion of discontinuers is still common yielding an increased risk of ischemic stroke (IS) onset. AIMS: We aimed to estimate the association between DOACs discontinuation and risk of IS among patients with non-valvular atrial fibrillation (NVAF). METHODS: We used data from a cohort of new DOACs users, followed patients from the first DOAC prescription date up to IS (index date) and conducted a nested case-control analysis using conditional logistic regression. Adjusted odds ratios, 95% confidence intervals were calculated for discontinuation of DOACs (current use compared with past use). The latter, subdivided among those stopping treatment 3 to 2 months and 6 and 3 months prior to index date. The effect of naïve current users against IS onset compared with non-naïve current users was also evaluated. RESULTS: DOACs discontinuation showed an OR of IS of 1.47 (95% CI: 1.02-2.12); estimates were 2.51 (95% CI: 1.84-3.42) for whom discontinued treatment within months 3 and 2 and 1.43 (95% CI: 0.96-2.13) for those between months 6 and 3 prior to index date. Analyzing DOACs individually, risk of IS associated with past users compared with current users: 1.98 (95% CI: 1.25-3.12) for apixaban, 1.38 (95% CI: 0.40-4.72) for edoxaban, 1.98 (95% CI: 1.24-2.65) for dabigatran and 1.87 (95% CI: 1.26-2.76) for rivaroxaban. Similar results were found when stratified by naïve and non-naïve users. CONCLUSIONS: DOACs' discontinuation is associated with higher risk of IS, especially in the second and third months following interruption.

Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

High-Resolution Three-Dimensional Imaging of the Footpad Vasculature in a Murine Hindlimb Gangrene Model.

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering from its most severe form, chronic limb-threatening ischemia (CLTI), face substantial impairments to daily living, including chronic pain, limited walking distance without pain, and nonhealing wounds. Preclinical models have been developed in various animals to study PAD, but mouse hindlimb ischemia remains the most widely used. There can be significant variation in response to ischemic insult in these models depending on the mouse strain used and the site, number, and means of arterial disruption. This protocol describes a unique method combining femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase (NOS) inhibitor to reliably induce footpad gangrene in Friend Virus B (FVB) mice that resembles the tissue loss of CLTI. While traditional means of assessing reperfusion such as laser Doppler perfusion imaging (LDPI) are still recommended, intracardiac perfusion of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is used to label the vasculature. Subsequent whole-mount confocal laser scanning microscopy allows for high-resolution, three-dimensional (3D) reconstruction of footpad vascular networks that complements traditional means of assessing reperfusion in hindlimb ischemia models.

Influence of biofilm thickness on the removal of thirteen different organic micropollutants via a Membrane Aerated Biofilm Reactor (MABR).

The presence of organic micropollutants (OMPs) in natural water bodies has become an emerging concern due to their fast dissemination into natural water sources, high persistence, ubiquitous nature, and detrimental impact on the environment and human health. This study evaluated the Membrane Aerated Biofilm Reactor (MABR) efficiency in the removal of 13 OMPs commonly reported in water. Results demonstrated that OMPs removal is dependent on biofilm thickness and bacterial cell density, microbial community composition and physicochemical properties of OMPs. Effective removals of ammonium and organic carbon (COD, >50%), acetaminophen (70%) and triclosan (99%) were obtained even at early stages of biofilm development (thickness < 0.33 mm, 2.9 ×105 cell mL-1). An increase in biofilm thickness and cell density (1.02 mm, 2.2 ×106 cell mL-1) enhanced the system performance. MABR achieved over 90% removal of nonpolar, hydrophobic and hydrophilic OMPs and 22-69% removal of negatively charged and acidic OMPs. Relative abundances of Zoogloea, Aquabacterium, Leucobacter, Runella, and Paludilbaculum bacteria correlated with the removal of certain OMPs. In addition, MABR achieved up to 96% nitrification and 80% overall COD removal by the end of the experiment. The findings from this study demonstrated MABRs to be a feasible option to treat municipal wastewater polluted by OMPs.

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015).

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Effectiveness of early versus delayed motion in patients with distal radius fracture treated with volar locking plate: A systematic review and meta-analysis.

The aim of this study was to determine the effectiveness of early versus delayed motion on the functional outcomes in patients with distal radius fracture (DRF) treated with a volar locking plate. A systematic review and meta-analysis of randomized clinical trials was performed. An electronic search was performed in the Medline, Central, Embase, PEDro, Lilacs, Cinahl, SPORTDiscus, and Web of Science databases. The eligibility criteria included randomized clinical trials that compared the effect of early versus delayed motion on wrist and/or upper limb function, pain, grip strength, and wrist range of motion in subjects older than 18 years with DRF treated with a volar locking plate. Five clinical trials were included that met the eligibility criteria for the quantitative synthesis. At 6 weeks, the PRWE questionnaire showed a mean difference (MD) of -10.6 points (p < 0.001), the MD was -11.1 points for the DASH questionnaire (p < 0.001), -0.56 cm for pain on VAS (p = 0.01), 5.0 kg for grip strength (p = 0.01), 12.5 degrees for wrist flexion (p = 0.07), and 12.8 degrees for wrist extension (p = 0.05). All differences favored the early motion treatment. At 3 months of follow-up, only the DASH, pain on VAS, and grip strength showed significant differences in favor of early motion. At 1 year of follow-up, none of the variables studied were different between groups. In the short term, there was moderate to high evidence of clinically and statistically significant differences in the functional outcomes in favor of early versus delayed motion in patients with DRF treated with a volar locking plate. But these differences were not observed at 1 year of follow-up. PROSPERO registration no.: CRD42020158706.

Granuloma anular perforante: patologia inusual / Perforating Granuloma Annulare: unusual pathology

Resumen El Granuloma Anular (GA) es una dermatosis inflamatoria crónica, benigna, auto limitada, de etiología desconocida. Existen numerosas variantes clínicas dentro de las cuales se encuentra la perforante, de presentación inusual. La histopatología más característica de GA, cuenta con la presencia de histiocitos epitelioides en empalizada alrededor de áreas de degeneración focal de fibras de colágeno con depósitos de mucina. La variedad perforante evidencia eliminación transepidérmica de fibras de colágeno. Se presenta un paciente de 72 años de edad, diabético, dislipémico, con lesiones pruriginosas en dorso de ambas manos, con el diagnóstico de granuloma anular perforante. Realizó tratamiento con clobetasol tópico, más antihistamínicos por vía oral, quedando una cicatriz atrófica.

Abstract Granuloma annulare is a chronic, benign, self-limiting, inflammatory dermatosis of unknown etiology. There are numerous clinical variants within which is the perforating, unusual presentation. The most histopathology characteristic of GA is the presence of palisading epithelioid histiocytes around areas of focal degeneration of collagen with mucin deposits. The perforating variety evidences transepidermal elimination of collagen tissue. A 72 years-old, diabetes, dyslipidemic patient is presented with pruritic lessions on the dorsum of both hands, with the diagnosis of perforating granuloma annulare. I perform medical treatment with topical clobetasol, leaving an atrophic scar.

Long-term efficacy of laparoscopic Nissen versus Toupet fundoplication for the management of types III and IV hiatal hernias.

BACKGROUND: Laparoscopic hiatal hernia repair via Toupet or Nissen fundoplication remains the most commonly performed procedures for management of large hiatal hernia. Few studies have compared the procedures' long-term effectiveness. This study sought to characterize the efficacy of laparoscopic Toupet versus Nissen fundoplication for types III and IV hiatal hernia. METHODS: With IRB approval, a review of all laparoscopic hiatal hernia repairs with mesh reinforcement performed over 7 years at a single center by one surgeon was conducted. Hiatal hernias were classified as type III or IV using operative reports and preoperative imaging. Patients with type I, II, or recurrent hiatal hernia and patients receiving concomitant procedures were excluded. The GERD-Health Related Quality of Life Survey was administered by telephone no earlier than 18 months postoperatively. RESULTS: A total of 473 patients underwent laparoscopic fundoplication; 179 having type III or IV hiatal hernia met inclusion criteria; 62 underwent Toupet, 117 underwent Nissen fundoplication. Average patient age was 64 years; 63% of patients were female. Cohorts were similar in demographics, comorbidities, and intraoperative factors. Survey was completed by 77 patients (43%): 50 having Nissen and 27 Toupet. Median time of survey completion after surgery was 54 months (Nissen) and 25 months (Toupet). Median survey responses across all items for both groups were 0 (no symptoms) with no significant variation between groups. Of patients that had Nissen, 26% reported current proton-pump inhibitor use versus 31% of Toupet patients (p = 0.486). Patient-reported satisfaction with current condition was similar between groups (67% Toupet, 72% Nissen, p = 0.351). CONCLUSIONS: Patient-reported symptoms and satisfaction did not vary for patients receiving laparoscopic Nissen versus Toupet fundoplication, which may indicate that patients with large type III and IV hiatal hernia undergoing either procedure have similar long-term postoperative symptom control.

Efectividad de las técnicas de movilización articular sobre el rango de movimiento de pacientes adultos con capsulitis adhesiva primaria de hombro: revisión sistemática y metanálisis / The effectiveness of joint mobilization techniques for range of motion in adult patients with primary adhesive capsulitis of the shoulder: a systematic review and meta-analysis

Resumen OBJETIVO: Determinar la efectividad de las técnicas de movilización articular en el rango de movimiento en pacientes adultos con capsulitis adhesiva primaria de hombro. MÉTODO: Revisión sistemática con metanálisis. La búsqueda fue realizada en las bases de datos MEDLINE/PubMed, PEDro, CENTRAL, LILACS, EMBASE, CINAHL, Scopus y Web of Science. Los criterios de elegibilidad fueron estudios que utilizaran una técnica de movilización articular oscilatoria y/o mantenida aplicada, sola o adicionada, a un programa de tratamiento en pacientes con capsulitis adhesiva primaria, en cualquier estadio. La selección de estudios y la extracción de datos fueron realizadas por dos autores de forma independiente. El riesgo de sesgo se evaluó según la herramienta propuesta por Cochrane. RESULTADOS: Se incluyeron 14 estudios con variados riesgos de sesgo. La movilización posterior versus otra técnica articular no presenta diferencia de media significativa (- 0,95 grados; intervalo de confianza de 95%; - 5,93 a 4,02), mientras que comparada con un grupo control la diferencia es de 26,80 grados (intervalo de confianza 95%; 22,71 a 30,89), además cuando se aplica un conjunto de técnicas articulares versus un grupo control, para la abducción la diferencia es de 20,14 grados (intervalo de confianza 95%; 10,22 a 30,05). En ambos casos, los resultados son estadísticamente significativos y se aprecia un tamaño de efecto moderado. CONCLUSIONES: La evidencia científica no es concluyente acerca de la efectividad de la movilización articular, dada la heterogeneidad en la metodología y sesgo de los artículos incluidos en esta revisión. Al compararla con tratamientos que no incluyen terapia manual, parecieran favorecer la mejoría del rango de movimiento y reducción del dolor, en pacientes con capsulitis adhesiva primaria de hombro.

Abstract OBJECTIVE: To determine the effectiveness of joint mobilization techniques in the range of motion in adult patients with primary adhesive shoulder capsulitis. METHODS: Systematic review with meta-analysis. The search was performed in the MEDLINE/PubMed, PEDro, CENTRAL, LILACS, EMBASE, CINAHL, Scopus and Web of Science databases. The eligibility criteria were studies that used an oscillatory and/or maintained joint mobilization technique applied alone or added-on to a treatment program in patients with primary adhesive capsulitis at any stage. Two authors carried out the selection of studies and the extraction of data, independently. Risk of bias was evaluated according to the tool proposed by Cochrane. RESULTS: We included 14 studies with variable risk of bias. Posterior mobilization compared to any other technique was not significantly different (0.95 degrees; 95% CI: - 5.93 to 4.02), whereas compared to a control group, the difference is 26.80 degrees (CI 95%: 22.71 to 30.89). When applying a set of joint techniques versus a control group, for abduction the difference is 20.14 degrees (95% CI: 10.22 to 30.05). In both cases, the results are statistically significant, and the effect size is moderate. CONCLUSIONS: The evidence is not conclusive about the effectiveness of joint mobilization. When compared with treatments that do not include manual therapy, joint mobilization seems to have a favorable effect on the range of motion and pain reduction in patients with primary adhesive shoulder capsulitis.

Influenza Virus Overcomes Cellular Blocks To Productively Replicate, Impacting Macrophage Function.

Whether influenza virus replication in macrophages is productive or abortive has been a topic of debate. Utilizing a panel of 28 distinct human, avian, and swine influenza viruses, we found that only a small subset can overcome cellular blocks to productively replicate in murine and primary human macrophages. Murine macrophages have two cellular blocks. The first block is during viral entry, where virions with relatively acid-stable hemagglutinin (HA) proteins are rendered incapable of pH-induced triggering for membrane fusion, resulting in lysosomal degradation. The second block is downstream of viral replication but upstream of late protein synthesis. In contrast, primary human macrophages only have one cellular block that occurs after late protein synthesis. To determine the impact of abortive replication at different stages of the viral life cycle or productive replication on macrophage function, we assessed cytotoxicity, nitric oxide or reactive oxygen species production, and phagocytosis. Intriguingly, productive viral replication decreased phagocytosis of IgG-opsonized bioparticles and Fc receptor CD16 and CD32 surface levels, a function, to our knowledge, never before reported for an RNA virus. These data suggest that replication in macrophages affects cellular function and plays an important role in pathogenesis during infection in vivo IMPORTANCE: Macrophages are a critical first line of defense against respiratory pathogens. Thus, understanding how viruses evade or exploit macrophage function will provide greater insight into viral pathogenicity and antiviral responses. We previously showed that only a subset of highly pathogenic avian (HPAI) H5N1 influenza virus strains could productively replicate in murine macrophages through a hemagglutinin (HA)-mediated mechanism. These studies expand upon this work and demonstrate that productive replication is not specific to unique HPAI H5N1 viruses; an H1N1 strain (A/WSN/33) can also replicate in macrophages. Importantly, we identify two cellular blocks limiting replication that can be overcome by an avian-like pH of activation for nuclear entry and a yet-to-be-identified mechanism(s) to overcome a postnuclear entry block. Overcoming these blocks reduces the cell's ability to phagocytose IgG-opsonized bioparticles by decreasing Fc receptor surface levels, a mechanism previously thought to occur during bacterial and DNA viral infections.

Eficacia de terapia fotodinámica como complemento de terapia convencional periodontal versus terapia convencional en el tratamiento de pacientes adultos con periodontitis crónica: una revisión sistemática con metaanálisis / Effectiveness photodynamic therapy complementing conventional periodontal therapy versus conventional therapy in the treatment of adult patients with chronic periodontitis: a systematic review with meta-analyses

Se evaluó la eficacia de la terapia fotodinámica como complemento de terapia periodontal convencional comparándola con la terapia convencional en el tratamiento de sacos periodontales en pacientes adultos con periodontitis crónica basándose en ensayos clínicos comprendidos entre los años 2010 y 2015, para determinar si su uso otorga mejores resultados para el tratamiento de esta enfermedad. Se seleccionaron ensayos clínicos aleatorios prospectivos, aleatorizados o no aleatorizados, controlados y no controlados que permitieron la comparación entre el tratamiento convencional y la terapia fotodinámica, con un grupo en el cual se utilizó sólo la terapia convencional. Los datos de los ensayos clínicos fueron ingresados al software Review Manager®. Se realizaron tres metaanálisis para las variables: Nivel de inserción clínica (NIC) y profundidad de sondaje (PS), el test de I2 fue utilizado para medir la heterogeneidad del estudio y posteriormente un análisis de sensibilidad para determinar los estudios heterogéneos. Se pudieron analizar 7 estudios, con un total de 186 pacientes, quienes fueron controlados 3 meses post tratamiento. Se utilizó la diferencia de medias, un intervalo de confianza de 95 % para medir el NIC y PS. A los 3 meses, no se encontró diferencias significativas en NIC (p= 0,93) y PS (p= 0,71). Conclusión: La terapia fotodinámica en complementación a la terapia convencional no otorga mejor resultado clínico ni estadístico comparado con la terapia convencional al evaluar el nivel de inserción clínica. Al evaluar la profundidad de sondaje es recomendable la utilización de terapia convencional sola.

The efficacy of photodynamic therapy as an adjunct to conventional periodontal therapy evaluated by comparing with conventional therapy alone in the treatment of periodontal pockets in adult patients with chronic periodontitis based on clinical trials between 2010 and 2015, to determine if its use can provide better results for treating this disease. Prospective randomized clinical trials and randomized clinical trials or non-randomized, controlled and uncontrolled that allowed comparison between a group which was applied to conventional therapy and photodynamic therapy, a similar group was selected to which you He applied only conventional therapy. Data from clinical trials entered into Review Manager®. Three meta-analyzes for the variables analyzed were performed: Level clinical attachment (NIC) and probing depth (PS), the test of I2 was used to measure the heterogeneity of the study and then a sensitivity analysis to determine which studies awardedheterogeneity. As results, seven studies analyzed in 186 patients who underwent treatment at least controlled within 3 months post treatment. The mean difference was used, a confidence interval of 95 % to measure the NIC and PS. At 3 months, no significant differences in NIC (p= 0.93) and PS (p= 0.71). In conclusion, the photodynamic therapy complementary to conventional therapy does not provide better clinical or statistical results compared with conventional therapy to evaluate the clinical attachment level. In assessing probing depth, is advisable to use conventional therapy alone.

Type I Interferon Response Limits Astrovirus Replication and Protects against Increased Barrier Permeability In Vitro and In Vivo.

UNLABELLED: Little is known about intrinsic epithelial cell responses against astrovirus infection. Here we show that human astrovirus type 1 (HAstV-1) infection induces type I interferon (beta interferon [IFN-ß]) production in differentiated Caco2 cells, which not only inhibits viral replication by blocking positive-strand viral RNA and capsid protein synthesis but also protects against HAstV-1-increased barrier permeability. Excitingly, we found similar results in vivo using a murine astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against astrovirus replication and pathogenesis in vivo. IMPORTANCE: Human astroviruses are a major cause of pediatric diarrhea, yet little is known about the immune response. Here we show that type I interferon limits astrovirus infection and preserves barrier permeability both in vitro and in vivo. Importantly, we characterized a new mouse model for studying astrovirus replication and pathogenesis.

Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.

BACKGROUND: For patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are scarce or missing. Hence, we aimed to compare seasonal changes in prescription rates of long-acting beta-2-agonist (LABA) in four European countries. METHODS: A common study protocol was applied to six health care databases (Germany, Spain, the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March, June, September, and December of each year during the study period 2002-2009. Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on the ratio-to-moving-average-method) and SIs averaged over the study period (aSI) stratified by sex, age, and indication (asthma, COPD, or ACOS). RESULTS: There was a moderate seasonal change in LABA-containing prescriptions which was more pronounced in asthma or COPD patients compared to ACOS patients. For asthma and ACOS patients, highest seasonal variation was found for patients living in Spain (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6). Regarding age and sex, highest seasonal variation was found in Spanish boys under 10 years of age having a diagnosis of asthma. CONCLUSIONS: By applying a common analysis in six databases, we could observe moderate overall seasonal changes in LABA-containing prescription rates in patients with asthma, COPD, or ACOS.

Giant hepatic hemangioma versus conventional hepatic hemangioma: clinical findings, risk factors, and management.

BACKGROUND: Giant hepatic hemangiomas (GHHs) are those that are larger than 4 cm in size. AIMS: The aim of this study was to describe GHH clinical findings, their risk factors, diagnostic approach and management, and to compare these data with those of conventional hemangiomas. METHODS: We performed a retrospective analysis of patients diagnosed with hemangiomas, whether by imaging studies or histopathology, at our hospital within the time frame of 1990-2008. The medical records of each patient were reviewed to obtain clinical and surgical data. RESULTS: Of the 57 patients with liver hemangioma, 41 (72%) were women and 32 (56%) had GHH. Liver hemangioma median size was 4.49 cm. In regard to the patients with GHH, 31.2% were asymptomatic and when symptoms presented, pain was the most common. Both symptoms and oral contraceptive exposure were more common in the GHH patients. Nine patients with GHH underwent surgery: 2 open biopsies due to diagnostic uncertainty, one enucleation, and 6 resections. CONCLUSIONS: GHHs are more prevalent in women and when symptomatic, pain is the most frequent complaint. Diagnosis is usually made through imaging studies, but when there is diagnostic doubt, surgical exploration is sometimes needed. Oral contraceptive use is most likely more of a risk factor for GHH than for conventional hemangioma, but this association needs to be studied further.

Ascertainment of acute liver injury in two European primary care databases.

PURPOSE: The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. METHODS: The Clinical Practice Research Datalink (CPRD) in UK and the Spanish "Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria" (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21%) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated. RESULTS: In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95% in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95% confidence interval (CI) 2.13-4.25) per 100,000 person-years than CPRD (1.35 (95% CI 1.03-1.78)). CONCLUSIONS: This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.

Antidepressant prescribing in five European countries: application of common definitions to assess the prevalence, clinical observations, and methodological implications.

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.

Incidence rates and trends of hip/femur fractures in five European countries: comparison using e-healthcare records databases.

Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4% per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.

The association of single nucleotide polymorphisms in the calcitonin gene with primary osteoarthritis of the knee in Mexican mestizo population.

Primary osteoarthritis (OA) is a multifactorial disorder with several genetics factors involved. Calcitonin (CT) has been suggested to possess chondroprotective effects and could play an important role in the pathogenesis of OA. The aim of this study was to investigate whether genetic variations in or adjacent to the CT gene may be associated with primary OA of the knee in Mexican mestizo population. We conducted a case-control study to investigate the association between six single nucleotide polymorphisms at the CT locus and OA of the knee in 107 cases and 106 controls. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee ≥ 2. Controls were subjects >40 years of age with a radiologic score <2. Non-conditional logistic regression was developed to evaluate risk magnitude. The G allele and GT genotype frequencies of the G-706T polymorphism and the C allele and CC genotype of the C-778T polymorphism were significantly higher in patients with OA than in control subjects. The GG genotype of the G-706T was associated with lower risk of the development of OA of the knee. According to the results, the G-706T and the C-778T polymorphisms were related to the Cdx1 and Mzf1 transcription factor binding sites, respectively. Therefore, these could be related to regulation sequences in the CT gene promoter. In conclusion, G-706T and C-778T polymorphisms in the CT gene are significantly associated with the development of primary OA of the knee.

SU-E-I-72: Modulation of Hypothalamic Connectivity by Food Ingestion.

PURPOSE: In this study we utilized resting state fMRI (rsfMRI) to identify and compare hypothalamic connectivity in lean subjects during fasting and satiated state. METHODS: rsfMRI were performed on 7 healthy lean subjects (4 male, 3 female, 20-35 yo, BMI = 18-25 kg/m2 ). Subjects fasted overnight (8 hrs), average blood glucose of 80± 5 mg/dL. None of the subjects were on diet program or recently lost/gain weight. rsfMRI EPI parameters:TR = 3000ms, TE = 30 ms, and spatial resolution of 1.7 × 1.7 mm × 5mm, ST= 65 mins (10-min pre-glucose ingestion acquisition, followed by 50 mins of post-glucose ingestion). During rsfMRI, subjects ingested standard glucola (75 g of glucose dissolved in 296 ml of flavored water) over 4.5 ± 0.75 min via a peroral rubber tube. Preprocessing procedure was implemented using FSL consisting of 1) motion correction 2) spatial smoothing, 3) temporal filtering between 0.01-0.08 Hz. Using the Talairach-Daemon atlas, ROI in the hypothalamus was selected. The individual timeseries of hypothalamus was used as seed to find neural structures that share similar temporal pattern that hypothalamus. RESULTS: Structures that were engaged only during fasting were (Table 1): Inferior frontal gyrus (BA 47) has been linked to the modulation of hunger. The output from the orbitofrontal cortex to both striatum (lentiform nucleus) and lateral hypothalamus has been reported. The structures that were engaged only during satiated state were: Superior temporal gyrus has been implicated in food inhibition and mid temporal gyrus has been reported to be engaged in satiation. Cerebellum is activated when the brain is monitoring its sensory systems.