Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve.

BACKGROUND: Vitamin K antagonists are the only oral anticoagulants approved to prevent valve thrombosis and valve-related thromboembolism in patients with mechanical heart valves. Whether patients with an On-X mechanical aortic valve can be safely anticoagulated with apixaban is unknown. METHODS: Patients with an On-X aortic valve implanted at least 3 months before enrollment were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). The primary efficacy end point was the composite of valve thrombosis or valve-related thromboembolism with coprimary analyses comparing apixaban with warfarin for noninferiority and comparing the apixaban event rate with an objective performance criterion (OPC). RESULTS: The trial was stopped after 863 participants were enrolled owing to an excess of thromboembolic events in the apixaban group. Most (94%) participants took aspirin. A total of 26 primary end-point events occurred, 20 (in 16 participants) in the apixaban group (4.2%/patient-year; 95% confidence interval [CI], 2.3 to 6.0) and 6 (in 6 participants) in the warfarin group (1.3%/patient-year; 95% CI, 0.3 to 2.3). The difference in primary end-point rates between the apixaban and warfarin groups was 2.9 (95% CI, 0.8 to 5.0); noninferiority and OPC success criteria were not met. Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin. CONCLUSIONS: Apixaban did not demonstrate noninferiority to warfarin and is less effective than warfarin for the prevention of valve thrombosis or thromboembolism in patients with an On-X mechanical aortic valve. (Funded by Artivion; ClinicalTrials.gov number, NCT04142658.)

Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve.

Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design. DESIGN: PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year. SUMMARY: PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.

Design and evaluation of a mobile application for monitoring patients with Alzheimer's disease: A day center case study.

BACKGROUND AND OBJECTIVE: This paper presents Alzheed, a mobile application for monitoring patients with Alzheimer's disease at day centers as well as a set of design recommendations for the development of healthcare mobile applications. The Alzheed project was conducted at Day Center "Dorita de Ojeda" that is focused on the care of patients with Alzheimer's disease. MATERIALS AND METHODS: A software design methodology based on participatory design was employed for the design of Alzheed. This methodology is both iterative and incremental and consists of two main iterative stages: evaluation of low-fidelity prototypes and evaluation of high-fidelity prototypes. Low-fidelity prototypes were evaluated by 11 day center's healthcare professionals (involved in the design of Alzheed), whereas high-fidelity prototypes were evaluated using a questionnaire based on the technology acceptance model (TAM) by the same healthcare professionals plus 30 senior psychology undergraduate students uninvolved in the design of Alzheed. RESULTS: Healthcare professional participants perceived Alzheed as extremely likely to be useful and extremely likely to be usable, whereas senior psychology undergraduate students perceived Alzheed as quite likely to be useful and quite likely to be usable. Particularly, the median and mode of the TAM questionnaire were 7 (extremely likely) for healthcare professionals and 6 (quite likely) for psychology students (for both constructs: perceived usefulness and perceived ease of use). One-sample Wilcoxon signed-rank tests were performed to confirm the significance of the median for each construct. CONCLUSIONS: From the experience of designing Alzheed, it can be concluded that co-designing with healthcare professionals leads to (i) fostering group endorsement, which prevents resistance to change and (ii) helps to meet the needs of both healthcare professionals and patients, guaranteeing the usefulness of the application. In addition, evaluation of mobile healthcare applications by users involved and uninvolved in the application's design process helps to improve the ease of use of the application.

Histiocitosis de células de Langerhans con afectación de la órbita en un lactante: reporte de un caso / Langerhans cell histiocytosis with orbital involvement in an infant: Case report

La histiocitosis de células de Langerhans es una enfermedad poco frecuente, caracterizada por la proliferación clonal de células dendríticas mieloides CD1a positivas, asociada a un componente inflamatorio significativo. El compromiso óseo es común; en niños, las lesiones líticas más frecuentes son en la cúpula craneal y son raras las lesiones en la órbita. Se presenta a un lactante de 18 meses que consultó por edema periorbitario y proptosis del ojo derecho de dos meses de evolución. Al momento del examen físico, no se encontraron otras alteraciones. Se realizó una tomografía y una resonancia magnética, que mostraron una masa tumoral en el seno maxilar de crecimiento expansivo y erosión del techo de la órbita. La biopsia confirmó la proliferación CD1a positiva; recibió tratamiento con prednisona y vinblastina, con evolución favorable. Un tratamiento precoz puede evitar secuelas significativas en los pacientes cuando son sensibles al tratamiento. Es una entidad poco frecuente que requiere un alto índice de sospecha y un manejo multidisciplinario.

The Langerhans cell histiocytosis is a rare disease characterized by the clonal proliferation of CD1a + myeloid dendritic cells associated with a significant inflammatory component. The localized form of the disease is called eosinophilic granuloma. Bone involvement is common; in children, lytic lesions are most frequently found in the cranial dome being rare in the orbit. We present an 18-month-old infant who consulted due to periorbital edema and proptosis of the right eye, with two months of evolution. The computed tomography and the magnetic resonance imaging showed a maxillary sinus tumor mass of expansive growth and erosion of the roof of the orbit. The biopsy confirmed CD1a+ proliferation; it was treated with prednisone and vinblastine with favorable evolution. It is a rare entity that requires a high index of suspicion and multidisciplinary management. Early diagnosis and treatment leads to a favorable prognosis for the patient.

[Langerhans cell histiocytosis with orbital involvement in an infant: Case report]. / Histiocitosis de células de Langerhans con afectación de la órbita en un lactante: reporte de un caso.

The Langerhans cell histiocytosis is a rare disease characterized by the clonal proliferation of CD1a + myeloid dendritic cells associated with a significant inflammatory component. The localized form of the disease is called eosinophilic granuloma. Bone involvement is common; in children, lytic lesions are most frequently found in the cranial dome being rare in the orbit. We present an 18-month-old infant who consulted due to periorbital edema and proptosis of the right eye, with two months of evolution. The computed tomography and the magnetic resonance imaging showed a maxillary sinus tumor mass of expansive growth and erosion of the roof of the orbit. The biopsy confirmed CD1a+ proliferation; it was treated with prednisone and vinblastine with favorable evolution. It is a rare entity that requires a high index of suspicion and multidisciplinary management. Early diagnosis and treatment leads to a favorable prognosis for the patient.

La histiocitosis de células de Langerhans es una enfermedad poco frecuente, caracterizada por la proliferación clonal de células dendríticas mieloides CD1a positivas, asociada a un componente inflamatorio significativo. El compromiso óseo es común; en niños, las lesiones líticas más frecuentes son en la cúpula craneal y son raras las lesiones en la órbita. Se presenta a un lactante de 18 meses que consultó por edema periorbitario y proptosis del ojo derecho de dos meses de evolución. Al momento del examen físico, no se encontraron otras alteraciones. Se realizó una tomografía y una resonancia magnética, que mostraron una masa tumoral en el seno maxilar de crecimiento expansivo y erosión del techo de la órbita. La biopsia confirmó la proliferación CD1a positiva; recibió tratamiento con prednisona y vinblastina, con evolución favorable. Un tratamiento precoz puede evitar secuelas significativas en los pacientes cuando son sensibles al tratamiento. Es una entidad poco frecuente que requiere un alto índice de sospecha y un manejo multidisciplinario.

Wet air oxidation of resorcinol as a model treatment for refractory organics in wastewaters from the wood processing industry.

Wastewater treatment systems are important tools to enhance sustainability in terms of reducing environmental impact and complying with sanitary requirements. This work addresses the wet air oxidation (WAO) process for pre-treatment of phenolic wastewater effluents. The aim was to increase biodegradability prior to a subsequent anaerobic stage. In WAO laboratory experiments using a micro-autoclave, the model compound resorcinol was degraded under different oxygen availability regims within the temperature range 150 °C-270 °C. The activation energy was determined to be 51.5 kJ/mol. Analysis of the products revealed that after 3 h of reaction at 230 °C, 97.5% degradation of resorcinol was achieved. At 250 °C and the same reaction time complete removal of resorcinol was observed. In this case the total organic carbon content was reduced down to 29%, from 118.0 mg/L down to 34.4 mg/L. Under these process conditions, the pollutant was only partially mineralized and the ratio of the biological oxygen demand relative to the chemical oxygen demand, which is 0.07 for resorcinol, was increased to a value exceeding 0.5. The main by-product acetic acid, which is a preferred compound for methanogenic bacteria, was found to account for 33% of the total organic carbon.

Cirugía Pediátrica en Cuba. Etapas de su desarrollo / Pediatric surgery in Cuba. Stages of its development

La historia de la Cirugía Pediátrica cubana está pendiente de ser documentada científicamente. Se estableció como objetivo definir las etapas de desarrollo de la especialidad en Cuba, para lo cual se hizo un análisis histórico y se identificó cuatro períodos fundamentales. Este artículo tiene una significación práctica puesto que permite conocer en qué momento se encuentra la especialidad para modelar el futuro de la misma(AU)

The history of Cuban pediatric surgery is pending of being scientifically documented. It was established as an objective to define the stages of the development of the specialty in Cuba. For this purpose a historical analysis was carried out and four main periods were identified. This study has a practical importance because it allows knowing the stage in which the specialty is to model its future(AU)

Cirugía Pediátrica en Cuba. Etapas de su desarrollo / Pediatric surgery in Cuba. Stages of its development

La historia de la Cirugía Pediátrica cubana está pendiente de ser documentada científicamente. Se estableció como objetivo definir las etapas de desarrollo de la especialidad en Cuba, para lo cual se hizo un análisis histórico y se identificó cuatro períodos fundamentales. Este artículo tiene una significación práctica puesto que permite conocer en qué momento se encuentra la especialidad para modelar el futuro de la misma.

The history of Cuban pediatric surgery is pending of being scientifically documented. It was established as an objective to define the stages of the development of the specialty in Cuba. For this purpose a historical analysis was carried out and four main periods were identified. This study has a practical importance because it allows knowing the stage in which the specialty is to model its future.

Albuterol delivery via metered dose inhaler in a spontaneously breathing pediatric tracheostomy model.

RATIONALE: Little data are available regarding efficiency of drug delivery devices and techniques despite their widespread use in spontaneously breathing tracheostomized patients. We compared patient dose achieved with different devices, inhalation techniques, tracheostomy tube sizes and breathing patterns using a spontaneously breathing tracheostomized pediatric model. METHODS: A tracheostomy model was connected in series to a breathing simulator with a filter interposed (patient dose). Breathing patterns of a 16-month-old and a 6- and 12-year-old child with tracheostomy with internal diameters (mm) of 3.5, 4.5, and 5.5 were used. Albuterol HFAp MDI was used. Aerotrach Plus, MediBag, Aerochamber MV, Aerochamber Mini, and inline adapter with 6-inch tubing were tested. The latter 3 devices were also tested with assisted technique. Albuterol was analyzed via spectrophotometry. RESULTS: Aerotrach Plus outperformed almost all devices tested. Aerochamber MV with unassisted technique was the second best and the adapter was the worst. Comparison of efficiency between best and worst performer ranged from 3- to 17.2-fold. The 16-month-old breathing pattern and the 3.5 mm tracheostomy tube had the lowest patient dose. The use of assisted technique decreased patient dose by 18-67% for the 4.5 and 5.5 mm but not for 3.5 mm tracheostomy tubes. A median of 7.4% of the nominal dose was deposited in the tracheostomy tubes. CONCLUSIONS: Aerotrach Plus and the adapter were the most and least efficient devices respectively. Tracheostomy size and breathing pattern affected drug delivery. The use of assisted technique reduced aerosol delivery.

The removal of microorganisms and organic micropollutants from wastewater during infiltration to aquifers after irrigation of farmland in the Tula Valley, Mexico.

The Tula Valley receives untreated wastewater from Mexico City for agricultural irrigation, half of which infiltrates to aquifers from where drinking water is extracted. Samples of wastewater and infiltrated water from three areas of the valley were analyzed for microorganisms, organic micropollutants, and some basic parameters. Concentrations of microorganisms in the infiltrated water were generally very low but the incidence of fecal coliforms (present in 68% of samples), somatic bacteriophages (36%), Giardia spp. (14%), and helminth eggs (8%) suggested a health risk. Organic micropollutants, often present at high concentrations in the wastewater, were generally absent from the infiltrated water except carbamazepine which was in 55% of samples (up to 193 ng/L). There was no correlation between carbamazepine concentrations and the presence of microorganisms but highest concentrations of carbamazepine and boron coincided. A treatment such as nanofiltration would be necessary for the infiltrated water to be a safe potable supply.

Accumulation and leaching potential of some pharmaceuticals and potential endocrine disruptors in soils irrigated with wastewater in the Tula Valley, Mexico.

The reuse of wastewater for irrigation of agricultural land is a well established practice but introduces many contaminants into the terrestrial environment including pharmaceuticals and personal care products. This study reports the persistence and leaching potential of a group of acidic pharmaceuticals, carbamazepine, and three endocrine disruptors in soils from the Tula Valley in Mexico, one of the largest irrigation districts in the world that uses untreated wastewater. After irrigation of soil columns with fortified wastewater over the equivalent of one crop cycle, between 0% and 7% of the total added amounts of ibuprofen, naproxen, and diclofenac and between 0% and 25% of 4-nonylphenol, triclosan, and bisphenol-A were recovered from the soil profiles. Carbamazepine was more persistent, between 55% and 107% being recovered. Amounts in leachates suggested that movement through the soil was possible for all of the analytes, particularly in profiles of low organic matter and clay content. Analysis of soil samples from the Tula Valley confirmed the general lack of accumulation of the acidic pharmaceuticals (concentrations from below the limit of detection to 0.61 µgkg(-1)) and endocrine disruptors (concentrations from below the limit of detection to 109 µgkg(-1)) despite continual addition through regular irrigation with untreated wastewater; there was little evidence of movement through the soil profiles. In contrast, carbamazepine was present in horizon A of the soil at concentrations equivalent to several years of additions by irrigation (2.6-7.5 µgkg(-1)) and was also present in the deeper horizons. The persistence and mobility of carbamazepine suggested a potential to contaminate groundwater.

Antibiotic hypersensitivity in CF: drug-induced life-threatening hemolytic anemia in a pediatric patient.

Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.

Effect of face mask dead volume, respiratory rate, and tidal volume on inhaled albuterol delivery.

INTRODUCTION: Pediatric patients often require metered-dose inhaler (MDI) with holding chamber (HC) to overcome lack of coordination when receiving inhaled therapy. In infants and young children unable to use a mouthpiece, it is necessary to use a mask interface. We compared the effect of varying mask static dead volume (SDV), respiratory rate (RR), and tidal volume (VT) on albuterol captured at the mouth opening (ACMO) in an in vitro model. METHODS: An Aerochamber Max(R) without and with three mask sizes (SDV of 10, 36, 85, and 200 ml, respectively) was connected in series to a filter holder and breathing simulator. ACMO was measured at VTs = 36, 72, 145, and 290 ml and RR of 12 and 24. Each experiment comprised 10 puffs run for six respiratory cycles each. Albuterol was quantified via spectrophotometry at 276 nm. A P-value of 0.05 was considered significant. RESULTS: Increasing VT increased ACMO (all SDVs and RRs). Adding SDV decreased ACMO, except for the small mask at VTs = 145 and 290 ml at RR = 12. Increasing SDV decreased ACMO, except at VT = 36 ml (all masks) and VT = 72 ml (small = medium) at RR = 12 and VT = 36 ml (small = other and medium > large) at RR = 24. Increasing RR increased ACMO for all SDVs at VTs = 36 and 72 ml, but not for VTs = 145 and 290 ml, except for no and large mask at VT = 145 ml. CONCLUSION: In general, decreasing SDV, increasing VT, and increasing RR increase ACMO. Early transition from face mask to mouthpiece should be considered in children receiving albuterol via MDI with HC.

Contamination of intravenous fluids: a continuing cause of hospital bacteremia.

BACKGROUND: Nosocomial bacteremia caused by the contamination of intravenous (IV) infusates is considered rare. Unfortunately, this problem has been underestimated because its identification requires culturing infusates, a procedure not performed routinely. METHODS: This study was conducted in a referral hospital where IV infusates are admixed in nursing areas. The aim was to determine the prevalence of infusate contamination in adult patients with gram-negative rod (GNR) bacteremia. Over a period of 32 months, a specimen of infusate was drawn for culture from each patient recruited after the laboratory reported a GNR in the blood. RESULTS: A total of 384 infusates were cultured from 384 patients who had been diagnosed with GNR bacteremia. Seven infusates grew a GNR in culture, for a contamination rate of 2% (7/384; 95% confidence interval [CI] = 1% to 3%). In all cases, the infectious organism was the same as the organism isolated from the blood. Infusate contamination was responsible for 7% (7/108; 95% CI = 2% to 11%) of all primary bloodstream infections and 11% (7/62; 95% CI = 2% to 22%) of all primary bloodstream infections not associated with central venous catheter infection. CONCLUSIONS: For patients in hospitals where IV drugs are admixed in nursing units, we recommend instituting infusate culture as routine practice following the diagnosis of a GNR in the blood.

Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy.

PURPOSE: The purpose of this study is to evaluate the demethylating and tumor suppressor-reactivating activity of hydralazine and procainamide. EXPERIMENTAL DESIGN: MDA-231, MCF-7, and T24 cell lines were treated for 5 days with 10 micro M hydralazine or 10 micro M procainamide. 5-aza-deoxycytidine at 0.75 micro M was used as positive control. BALB/c nu/nu mice xenografted with MDA-231 cells were treated with these drugs for 7 days by i.p. route. Methylation was assessed by PCR after digestion with methylation-sensitive enzymes for the ER gene and with methylation-specific PCR for retinoic acid receptor (RAR)beta and p16 genes. Gene expression was evaluated by reverse transcription-PCR and Western blot. The duration of the gene re-expressing effect of hydralazine was analyzed on T24 cells. Functionality of the re-expressed proteins was evaluated by the induction of the estrogen-responsive gene PS2 on MDA-231 cells and by the induction of G(1) arrest on T24 cells. The gene demethylating and re-expressing ability of hydralazine was tested in two patients with cervical and head and neck carcinomas, respectively. RESULTS: Hydralazine and procainamide induced de-methylation and re-expression of the ER, RARbeta, and p16 genes in cultured cells. Both drugs also demethylated and re-expressed the ER gene in mice. Hydralazine re-expressed the p16 gene longer as compared with 5-aza-deoxycytidine. The re-expressed genes were functional. In addition, the treatment with oral hydralazine demethylated and re-expressed the RARbeta and p16 genes in the cervical and head and cancer patients. CONCLUSIONS: These cardiovascular drugs have a promising tumor suppressor-reactivating action and could potentially be used in clinic as an anticancer treatment, most likely to increase the efficacy of current biological or chemotherapeutic treatments.