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Background Anticoagulant therapy for venous thromboembolism (VTE) in children is largely based on treatment recommendations for adults. However, differences in both physiology (ie, renal maturation and drug excretion) and developmental hemostasis must be considered when treating children, as such differences could affect dose appropriateness, safety and efficacy. Objectives To address these concerns, a study was designed to evaluate the safety of dabigatran etexilate in children requiring secondary thrombus prevention in whom an initial VTE was associated with an identified risk factor that persisted after the acute VTE treatment period. We report herein the rationale and design of the study. Patients/Methods This phase 3, open‐label, single‐arm, multicenter, multinational, prospective cohort study will be conducted in ≥100 children aged 0 to

Essentials Current standard of care (SOC) for pediatric venous thromboembolism (VTE) has limitations.Dabigatran etexilate (DE) versus SOC will be studied in children with VTE in a phase IIb/III trial.A dosing algorithm for DE in children will be assessed guiding dosing.Valuable data on the safety and efficacy of DE for VTE in children will be obtained. Background The current standard of care (SOC) for pediatric venous thromboembolism (VTE) comprises unfractionated heparin (UFH), or low‐molecular‐weight heparin (LMWH) followed by LMWH or vitamin K antagonists, all of which have limitations. Dabigatran etexilate (DE) has demonstrated efficacy and safety for adult VTE and has the potential to overcome some of the limitations of the current SOC. Pediatric trials are needed to establish dosing in children and to confirm that results obtained in adults are applicable in the pediatric setting. Objectives To describe the design and rationale of a planned phase IIb/III trial that will evaluate a proposed dosing algorithm for DE and assess the safety and efficacy of DE versus SOC for pediatric VTE treatment. Patients/Methods An open‐label, randomized, parallel‐group noninferiority study will be conducted in approximately 180 patients aged 0 to

Essentials Dabigatran etexilate may provide a new treatment option for pediatric venous thromboembolism. Children aged 1 to < 12 years were given dabigatran etexilate in an open-label, single-arm study. The pharmacokinetic–pharmacodynamic relationship was similar to that seen in adult patients. There were no serious adverse events, bleeding events or recurrent venous thromboembolism. SummaryBackground The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations. Dabigatran etexilate (DE), a direct thrombin inhibitor, may offer an alternative therapeutic option. Objectives To assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of a DE oral liquid formulation (OLF) in pediatric patients with VTE. Patients/Methods Patients who had completed planned treatment with low molecular weight heparin or oral anticoagulants for VTE were enrolled in two age groups (2 to < 12 years and 1 to < 2 years), and received a DE OLF based on an age-adjusted and weight-adjusted nomogram. Originally, patients were to receive a DE OLF twice daily for 3 days, but the protocol was amended to a single dose on day 1. The primary endpoints were pharmacokinetics/pharmacodynamics-related: plasma concentrations of DE and its metabolites; activated partial thromboplastin time (APTT), ecarin clotting time (ECT), and dilute thrombin time (dTT); and pharmacokinetic (PK)–pharmacodynamic (PD) correlation. Safety endpoints included incidence rates of bleeding events and all other adverse events (AEs). Results Eighteen patients entered the study and received the DE OLF (an exposure equivalent to a dose of 150 mg twice daily in adults). The projected steady-state dabigatran trough concentrations were largely comparable between pediatric patients and adults. The PK/PD relationship was linear for ECT and dTT, and non-linear for APTT. No serious or severe AEs, bleeding events, or recurrent VTEs were reported. Mild AEs were reported in three patients in the single-dose group (screening period) and in one patient in the multiple-dose group (on-treatment period). Conclusion The current study supports the further evaluation of DE OLFs in pediatric patients with VTE.

Venous thromboembolism (VTE) is more frequent in infants than in older children. Treatment guidelines in children are adapted from adult VTE data, but do not currently include direct oral anticoagulant use. Dabigatran etexilate (DE) use in the paediatric population with VTE therefore requires verification. We investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationship, safety and tolerability of DE oral liquid formulation (OLF) in infants with VTE (aged

Aim This study is a narrative inquiry that aims to better understand the experience of nurses implementing a Person-Centred Care (PCC) bundle onto an acute care ward in a large hospital in Melbourne, Australia. Background The PCC includes five key focus areas aimed at streamlining nursing practice 1) Nursing assessment and care planning, 2) bedside handover, 3) patient safety rounding, 4) patient whiteboards, and 5) safety huddles. The PCC bundle outlines a nursing care process that is interactional with the patient, focused on information sharing, safety and respect. Method A narrative inquiry was used to explore the nurse's experiences implementing the PCC. Surveys and focus groups were used to collect data and thematic analysis was used to identify any key themes. Results The three themes were; Passing the baton; Keeping the cogs moving when time poor; and Deep interpersonal relating-The sum of us.

This chapter explores Facebook.com's current and potential uses for increasing college student involvement. Ideas based on Astin's model of student involvement provide a framework for discussion.

A prospective review of 158 enterally fed intensive care unit (ICU) patients at the University of Kentucky Medical Center revealed a significant variation in the clinical approach to the diagnosis and management of diarrhea. A standard definition for diarrhea was necessary to develop a cost-effective approach to this problem. A rational treatment algorithm was established for the diagnosis and management of diarrhea in the enterally fed ICU patient.

Fresh Start, a career development project in Rapid City, South Dakota focusing on Native American parolees with multiple barriers to employment, was effective in placing 75% of its 1994 group in Jobs. Clients reported that feeling valued and important was the most important aspect of the experience.

Combining silver-based dressings with negative pressure therapy after radical excision of chronically infected breast disease is a novel application of two technologies. One patient with complex, chronic, infected breast disease underwent radical excision of the affected area and was treated early with a combination of silver-based dressings and topical negative pressure therapy. The wound was then assessed sequentially using clinical measurements of wound area and depth, pain severity scores and level of exudation. It is possible to combine accepted techniques with modern dressing technologies that result in a positive outcome. In this case, the combination of a silver-based dressing with negative pressure therapy following radical excision proved safe and was well tolerated by the patient. Full epithelisation of the wound was achieved and there was no recurrence of the infection for the duration of the treatment.

BackgroundDabigatran is an oral direct thrombin inhibitor that has been shown to be an effective alternative to warfarin in patients with atrial fibrillation. We evaluated the use of dabigatran in patients with mechanical heart valves. MethodsIn this phase 2 dose-validation study, we studied two populations of patients: those who had undergone aortic- or mitral-valve replacement within the past 7 days and those who had undergone such replacement at least 3 months earlier. Patients were randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. The selection of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on kidney function. Doses were adjusted to obtain a trough plasma level of at lea ResultsThe trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. In the as-treated analysis, dose adjustment or discontinuation of dabigatran was required in 52 of 162 patients (32%). Ischemic or unspecified stroke occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin group; major bleeding occurred in 7 patients (4%) and 2 patients (2%), respectively ConclusionsThe use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk. (Funded by Boehringer Ingelheim; ClinicalTrials.gov numbers, NCT01452347 and NCT01505881.) In a phase 2 trial, patients with mechanical heart valves were randomly assigned to receive either dabigatran or warfarin for anticoagulation. Dabigatran was associated with higher rates of ischemic stroke (5%, vs. 0% with warfarin) and major bleeding (4% vs. 2%). Prosthetic heart-valve replacement is recommended for many patients with severe valvular heart disease and is performed in several hundred thousand patients worldwide each year.(1) Mechanical valves are more durable than bioprosthetic

Background: Venous thromboembolism (VTE) events are more frequent in neonates than in children of other age groups. The standard of care for pediatric anticoagulation includes unfractionated or low-molecular-weight heparin, or vitamin K antagonists. However, these treatments have limitations in terms of practicality of use in infants, such as parenteral administration, frequent monitoring and drug interactions. Alternative oral agents that address these shortcomings may improve compliance, efficacy and safety. The safety and efficacy of dabigatran etexilate (DE), a direct thrombin inhibitor, are established in adults; pharmacokinetic/pharmacodynamic (PK/PD) studies indicate linear PK. There is a relationship between dabigatran plasma concentration (PK) and its PD effects, resulting in reproducible dose-dependent prolongation in clotting times with rapid onset and offset of effect, which is consistent across populations. Although phase IIa studies suggest a similar PK/PD relationship of dabigatran in children and adults, the hemostatic system in infants differs from older children and adults, which may lead to a different PK/PD effect. Objective: To demonstrate comparable PK/PD relationship of DE oral liquid formulation (OLF) between infants and older children and adults, and to assess safety and tolerability. Methods: Open-label, multicenter, single-dose, single-arm, phase IIa pediatric study. Infants aged < 1 year diagnosed with VTE who completed standard anticoagulant treatment for VTE were enrolled. Exclusion criteria included < 37 weeks gestational age at birth, weight < 3 kg, major bleed with standard anticoagulant and swallowing abnormalities. Patients received DE OLF (based on age- and weight-adjusted nomogram) and were followed up for 30 (+7) days. The primary endpoints were PK/PD related, measured at 2 hrs and 12 (±2) hrs after DE administration. The PK endpoint was plasma concentration of total dabigatran, and PD endpoints were activated partial thromboplastin time (aPTT), ecarin clotting time (ECT) and diluted thrombin time (dTT). Secondary endpoints included incidence of all bleeding events and adverse events (AEs), acceptability and tolerability. Descriptive statistics were applied to the endpoints. PK/PD relationship was analyzed using a simple linear regression model and nonlinear Emax model to confirm whether models used in previous studies were consistent with the pediatric data of this study. Results: Ten patients were screened and 8 entered the study (mean age [SD]: 89 [52] days; range: 41-169 days). Patients received a single dose of DE OLF. The geometric mean (gMean) total dabigatran plasma concentrations 2 hrs post dose (around peak concentrations) was 120 ng/mL with geometric coefficient of variation (gCV) of 62.1%, which indicated moderate variability. The gMean at 12 hrs post dosing was 60.4 ng/mL (gCV 30%), which indicated low variability. The projected steady-state dabigatran trough concentrations were largely comparable to those observed in adults with VTE (Table). A linear PK/PD relationship was observed for ECT (ECT ratio) and dTT (dTT ratio) (Figure). The relationship between total dabigatran concentration and aPTT (aPTT ratio) was nonlinear. The observed PK/PD relationships were similar to those in adult and adolescent patients with VTE, except for patients aged < 2 months, in whom a slight upward shift of aPTT of 10-20% (average) and ECT by 10-15% was observed relative to adults. There were no AEs, deaths or treatment discontinuations during the treatment period. None of the treated patients had any bleeding events or thromboembolic events during the study. One patient had a serious AE (aortic stenosis) during the post-treatment period, which was not considered treatment related by the investigator. There were no clinically relevant or unexpected laboratory findings. The majority of patients were assessed with good tolerability (six patients, 75%), and one patient each (12.5%) was evaluated with satisfactory or bad tolerability. Conclusion: In this small population of infants (aged < 1 year), DE OLF was well tolerated without any treatment-related AEs, thromboembolic or bleeding events. The observed PK/PD relationships were consistent with the established profile in adult and adolescent patients with VTE. Disclosures Halton: Boehringer Ingelheim: Other: Pediatric Expert Working Group for Boehringer Ingelheim. Picard:Boehringer Ingelheim: Employment. Harper:Boehringer Ingelheim: Employment. Huang:Boehringer Ingelheim: Employment. Brueckmann:Boehringer Ingelheim: Employment. Gropper:Boehringer Ingelheim: Employment. Maas:Boehringer Ingelheim: Employment. Tartakovsky:Boehringer Ingelheim: Employment. Nurmeev:Boehringer Ingelheim: Other: Investigator fees. Mitchell:Boehringer Ingelheim: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy. Albisetti:Boehringer Ingelheim: Other: Pediatric Expert Working Group.

Objective To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval. Patients and methods In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Secondary endpoints included changes in 24-h, morning, daytime and night-time mean ambulatory BP and ambulatory BP response rates. Results Telmisartan 80 mg produced greater reductions in the last 6-h mean ambulatory SBP and DBP compared with ramipril 5 mg (P < 0.0001) and 10 mg (P< 0.0001), and was superior to ramipril for all secondary ambulatory SBP and DBP endpoints (P

Section 5(2) of the Mental Health Act, 1983 allows for the detention of an informal in-patient, should he/she wish to leave hospital but be considered a danger to him/herself or others if allowed to do so. The 72 hour period of detention allows time for a completed assessment for application for admission under Section 2 or 3 of the Act; it is not intended to replace this fuller assessment. The 1983 Mental Health Act introduced new provisions with regard to Section 5(2). The equivalent Section 30 of the Mental Health Act 1959 did not provide for a nominated deputy to act on behalf of the registered medical practitioner in charge of the patient's treatment (RMP). The nominee must exercise his/her own clinical judgement but, as indicated in the Code of Practice (1990), must contact the nominating doctor or another consultant to discuss the need for Section 5(2), before implementing it. The nurses' holding power, Section 5(4), was also a new provision in the 1983 Act.

Background Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement. Objective This study aims to test a new dosing regimen for dabigatran etexilate in patients with a mechanical bileaflet valve. Methods Patients aged ≥18 years and ≤75 years, either undergoing implantation of a mechanical bileaflet valve (aortic or mitral or both) during the current hospital stay or having undergone implantation a mitral bileaflet valve >3 months before randomization, will be randomized between dabigatran etexilate or warfarin (in a ratio of 2:1) in an open-label design. Initial doses of dabigatran will be based on the estimated creatinine clearance, and the doses will be adjusted based on measuring trough dabigatran plasma levels to achieve levels ≥50 ng/mL at steady state. Doses will range between 150 mg twice a day and 300 mg twice a day. Warfarin management and target international normalized ratio will be according to current practice guidelines at the discretion of the treating physicians. The plan is to treat 270 patients with dabigatran etexilate for a total study population of approximately 405 patients. Clinical efficacy and safety outcomes will be analyzed in an exploratory manner. Conclusions RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study.

In a psychiatric census of a 196-bed acute inpatient Medicine for the Elderly unit, 76.1% of patients resident during 1 week were screened and interviewed in a two-stage diagnostic procedure. Of 153 patients studied, 11.1% were delirious, 26.8% were demented, and 9.2% were depressed. Overall, 56.9% of the cases were identified by ward nurses, and 55.5% by the ward doctors; taken together, ward staff identified 75.0% of the cases (kappa = 0.46), indicating that detection of psychiatric disorder in this population might be improved if doctors and nurses pooled their observations on this aspect of patient assessment.

An 80-year-old widow with delusional infestation in association with post-herpetic neuralgia and EEG abnormalities in the left anterior parietal lobe responded to combined pimozide and carbamazepine. Aetiological factors are reviewed in relation to the literature.

EDITOR—Dickenson's article on genetic testing for adult onset disorders in young people raises an important issue,1 but her statement that “many clinical genetics units operate a bar at 18” suggests a lack of familiarity with current practice in clinical genetics and the way it has evolved since genetic testing for adult onset disorders became feasible. She is right to distinguish the situation of adolescents requesting testing from that of parental …