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Contains fulltext : 219893.pdf (Publisher’s version ) (Closed access) BACKGROUND: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children /=1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0.40, 95% CI 0.11-1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0.012). Major or clinically relevant non-major bleeding in participants who received >/=1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1.58, 95% CI 0.51-6.27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING: Bayer AG and Janssen Research & Development. 01 januari 2020

Dogs are a popular pet in the United Kingdom, and walking a dog is widely recognized as an important part of dog ownership. A number of different restraints can be used when walking dogs on leashes, such as collars and harnesses. Previous research has examined the behavioral effects of walking dogs on head and neck collars. Harnesses are often anecdotally proposed to be more beneficial to dog welfare than other alternative restraints; however, to date, the effects of walking dogs on harnesses have not been investigated. The aim of this study was to determine the behavioral responses of dogs walked on neck collars or harnesses. The broader purpose of this study was to examine if the type of restraint worn causes stress in dogs. To explore this, a within-subject counterbalanced design was used. Thirty privately owned dogs were recruited within 2 groups (each group: n = 15); those previously walked on a harness and those previously walked on a neck collar. Dogs were walked for 20 minutes each while behavioral indicators of stress were recorded. After this trial, owners were given the alternative walking restraint and returned a week later to perform a second 20-minute walk. Behavioral indicators were again recorded. No significant differences were found between behaviors shown by dogs when walked on either collar or harness. However, dogs with a history of being walked on a collar showed increased low ear position. This may suggest that these dogs are more stressed; however, because of the lack of support from the other stress indicators, motivations, such as indicating appeasement toward their owners, should also be considered. These findings suggest that, at least for the specific harness and collar trialed, neither neck collars nor harnesses are eliciting stress in dogs. However, future research determining the long-term effects of neck collar and harness use would be beneficial.

Standard treatment for Glanzmann thrombasthenia is platelet transfusion. Recombinant activated factor VII has been shown to be successful in patients with Glanzmann thrombasthenia with platelet antibodies or who are refractory to platelet transfusions. The Glanzmann Thrombasthenia Registry prospectively collected worldwide information on the effectiveness and safety of platelet transfusion, recombinant activated factor VII and/or antifibrinolytics for the treatment of bleeds in patients with Glanzmann thrombasthenia. Data relating to 829 non-surgical bleeding episodes were entered into the Glanzmann Thrombasthenia Registry (severe/moderate: 216/613; spontaneous/post-traumatic: 630/199). Recombinant activated factor VII alone was used in 124/829 bleeds, recombinant activated factor VII+antifibrinolytics in 107/829, platelets±antifibrinolytics in 312/829, antifibrinolytics alone in 219/829, and recombinant activated factor VII+platelets±antifibrinolytics in 67/829. The proportion of successful treatments to stop bleeding was 91.0% in cases treated with recombinant activated factor VII only, 82.7% for recombinant activated factor VII+antifibrinolytics, 72.7% for treatment with recombinant activated factor VII+platelets±antifibrinolytics, 78.8% for platelets±antifibrinolytics and 84.7% for antifibrinolytics alone. Treatment failure was documented in 18 bleeding events (2% of the total treatments), the majority of which were in patients receiving treatment with antifibrinolytics; bleeding re-started in 6% of bleeds after initial effective treatment. Thirty-five adverse events were reported, none of which was a thromboembolic event. Among treatments that included recombinant activated factor VII, only one patient reported three possibly drug-related non-serious adverse events (nausea, dyspnea and headache). To conclude, non-surgical bleeds were common and often severe in Glanzmann thrombasthenia; both platelets and recombinant activated factor VII appeared to be effective, and with good safety profiles, for the treatment of non-surgical bleeds. This trial was registered at clinicaltrials.gov identifier: NCT01476423.

Standard treatment for Glanzmann thrombasthenia, a severe inherited bleeding disorder, is platelet transfusion. Recombinant factor VIIa is reported to be effective in Glanzmann thrombasthenia with platelet antibodies and/or refractoriness to platelet transfusions. We aimed to evaluate recombinant factor VIIa effectiveness and safety for the treatment and prevention of surgical bleeding in patients, with or without platelet antibodies and/or refractoriness, using data from the Glanzmann Thrombasthenia Registry, an international, multicenter, observational, post-marketing study of rFVIIa. Between 2007 and 2011, 96 patients were treated for 206 surgical procedures (minor 169, major 37). History of platelet antibodies was present in 43 patients, refractoriness in 23, antibodies+refractoriness in 17, while 47 had no confirmed antibodies/refractoriness. Treatments analyzed included antifibrinolytics, recombinant factor VIIa, recombinant factor VIIa+antifibrinolytics, platelets±antifibrinolytics and recombinant factor VIIa+platelets±antifibrinolytics. The most frequent treatment for minor procedures was recombinant factor VIIa+antifibrinolytics (n=65), and for major procedures, recombinant factor VIIa+platelets±antifibrinolytics (n=13). In patients without antibodies/refractoriness, recombinant factor VIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for minor and major procedures. The effectiveness of treatment for minor procedures in patients with antibodies and refractoriness was 88.9% for recombinant factor VIIa, 100% for recombinant factor VIIa+antifibrinolytics, 66.7% for platelets±antifibrinolytics and 100% for recombinant factor VIIa+platelets±antifibrinolytics. One of four adverse events reported for surgery was considered recombinant factor VIIa-treatment-related (non-fatal thromboembolic event in an adult female receiving recombinant factor VIIa+platelets+antifibrinolytics). For all patients, regardless of platelet antibody or refractoriness status, recombinant factor VIIa, administered with or without platelets (±antifibrinolytics), provided effective hemostasis with a low frequency of adverse events in surgical procedures in Glanzmann thrombasthenia patients. This trial was registered at clinicaltrials.gov identifier: 01476423.

Objective To evaluate the effects of a therapeutic outcomes monitoring (TOM) program on selected process and outcome measures. Design Prospective, controlled, multicenter study. Setting Community pharmacies throughout Denmark (16 intervention, 15 control). Patients Five hundred patients with asthma aged 16 to 60 years and treated in primary care. Intervention TOM is a community-based program for pharmaceutical care. Using a structured, seven-step, cyclical outcome improvement process, TOM pharmacists identify and resolve (or refer) problems with drug therapy that, if not addressed, might result in therapeutic failure or adverse effects. Equal emphasis is placed on the patient's perspective (e.g., coping, control, and empowerment) and the professional's perspective (e.g., adherence, patient knowledge, and therapeutic problems). TOM requires cooperation among pharmacists, patients, and physicians. Main Outcome Measures Asthma symptom status, days of sickness, health-related and asthma-specific quality of life, use of health care services and resources, and satisfaction with health care and pharmacy. Intermediate Outcome and Process Measures Peak expiratory flow rate (PEFR), knowledge of asthma and asthma medications, inhalation errors, and drug therapy problems in the TOM group. Results The mean individual differences for TOM and control patients were tested. Beneficial effects were found for the following outcome measures: asthma symptom status, days of sickness, and health-related and asthma-related quality of life. Satisfaction with health care and pharmacy varied throughout the course of the project, with no significant difference between groups at the final evaluation. Although not statistically significant, differences in use of services were considered to be clinically significant and encouraging. Beneficial effects were found for knowledge of asthma and medications, inhalation errors, drug use and drug therapy problems. No significant differences were found for PEFR. Conclusion The project demonstrated that therapeutic outcomes monitoring by community pharmacists is an effective strategy for improving the quality of drug therapy for asthma patients in primary health care.

Background Respiratory distress syndrome remains a significant problem among premature infants. Mechanical ventilation through an endotracheal tube remains the mainstay of respiratory support but may be associated with lung injury and the development of chronic lung disease of prematurity. Efforts are needed to reduce the duration of mechanical ventilation in favour of less invasive forms of respiratory support and to improve rates of successful extubation. Non-invasive respiratory support has been demonstrated to be less injurious to the premature lung. Standard practice is to use nasal continuous positive airway pressure (n-CPAP) following extubation to support the baby's breathing. Many clinicians also use nasal biphasic positive airway pressure (n-BiPAP) in efforts to improve rates of successful extubation. However, there is currently no evidence that this confers any advantage over conventional nasal continuous positive airway pressure. Methods We propose an unblinded multi-centre randomised trial comparing n-CPAP with n-BiPAP in babies born before 30 weeks' gestation and less than two weeks old. Babies with congenital abnormalities and severe intra-ventricular haemorrhage will be excluded. 540 babies admitted to neonatal centres in England will be randomised at the time of first extubation attempt. The primary aim of this study is to compare the rate of extubation failure within 48 hours following the first attempt at extubation. The secondary aims are to compare the effect of n-BiPAP and n-CPAP on the following outcomes: 1. Maintenance of successful extubation for 7 days post extubation 2. Oxygen requirement at 28 days of age and at 36 weeks' corrected gestational age 3. Total days on ventilator, n-CPAP/n-BiPAP 4. Number of ventilator days following first extubation attempt 5. pH and partial pressure of carbon dioxide in the first post extubation blood gas 6. Duration of hospital stay 7. Rate of abdominal distension requiring cessation of feeds 8. Rate of apnoea and bradycardia 9. The age at transfer back to referral centre in days The trial will determine whether n-BiPAP is safe and superior to n-CPAP in preventing extubation failure in babies born before 30 weeks' gestation and less than two weeks old. Trial registration number ISRCTN: ISRCTN18921778

Objective: To design a pharmaceutical care model, and develop and field test a set of community pharmacy guidelines and practice support materials-Therapeutic Outcomes Monitoring (TOM) modules. Design: Concept interviews with pharmacists, physicians, and patients; development and field testing of practice guidelines. Setting: Community pharmacies. Participants: Five independent, five chain, and two clinic site pharmacies. Interventions: A prototype TOM module for asthma was developed through a seven-step process. Concept interviews were held with pharmacists, physicians, and patients to determine the desirability and feasibility of the TOM concept, prototype, and materials. Two field tests were completed and modifications made. Results were gathered through further concept interviews at the completion of the second field tests. Main Outcome Measures: Participants' opinions and experiences. Results: Pharmacists, physicians, and patients expressed favorable attitudes about community pharmacists' participation in this pharmaceutical care model. Of the 12 participating pharmacists, 7 successfully implemented TOM in their practice sites and participated in the project throughout the testing; 49 patients were recruited into the study; and 22 patients remained in the program at the end of the second field test. In providing TOM services to these patients, the two most problematic areas for the pharmacists were in documenting care and reporting to physicians. A final phase of the TOM project has not been conducted in the United States because of insufficient numbers of patients for evaluating patient outcomes. Conclusion: The TOM project was successful from a technical but not a marketing perspective. Useful practice guidelines can be written and taught to pharmacists. Enrollment of patients was difficult, and the concept is not likely to spread spontaneously within the existing market for pharmaceutical services.

Immature inflorescence culture and subsequent plant regeneration was practiced for four successive cycles using a Triticum crassum × Hordeum vulgare hybrid cultured on Kao's medium supplemented with 2,4-dichlorophenoxyacetic acid (5 mg/mL). In one line, chromosomal mixoploidy was observed among both mitotic and meiotic cells. Variation in chromosome number of 20 to 98 was observed in mitotic and 14 to 68 among meiocytes in the first cycle regenerants. The range in chromosome number decreased in subsequent regeneration cycles. Fragmented chromosomes were observed at low frequencies in both groups of cells. The high frequency of univalents at meiosis was attributed to possible elimination of chromosomes carrying meiotic pairing control genes.Key words: somaclonal variation, hybrids (intergeneric), tissue culture, chromosomal mixoploidy.