Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin) : study protocol for a randomized controlled trial

Peer reviewedPublisher PD

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine

Supporting Treatment Adherence Readiness through Training (START) for patients with HIV on antiretroviral therapy: study protocol for a randomized controlled trial.

BackgroundFew HIV antiretroviral adherence interventions target patients before they start treatment, assess adherence readiness to determine the timing of treatment initiation, or tailor the amount of adherence support. The Supporting Treatment Adherence Readiness through Training (START) intervention, based on the information-motivation-behavioral skills model of behavior change, is designed to address these gaps with the inclusion of (1) brief pill-taking practice trials for enhancing pretreatment adherence counseling and providing a behavioral criterion for determining adherence readiness and the timing of treatment initiation and (2) a performance-driven dose regulation mechanism to tailor the amount of counseling to the individual needs of the patient and conserve resources. The primary aim of this randomized controlled trial is to examine the effects of START on antiretroviral adherence and HIV virologic suppression.Methods/designA sample of 240 patients will be randomized to receive START or usual care at one of two HIV clinics. Primary outcomes will be optimal dose-taking adherence (>85 % prescribed doses taken), as measured with electronic monitoring caps, and undetectable HIV viral load. Secondary outcomes will include dose-timing adherence (>85 % prescribed doses taken on time) and CD4 count. Primary endpoints will be month 6 (short-term effect) and month 24 (to test durability of effect), though electronic monitoring will be continuous and a fully battery of assessments will be administered every 6 months for 24 months.DiscussionIf efficacious and cost-effective, START will provide clinicians with a model for assessing patient adherence readiness and helping patients to achieve and sustain readiness and optimal treatment benefits.Trial registrationClinicalTrials.gov identifier NCT02329782 . Registered on 22 December 2014

A safer place for patients: learning to improve patient safety

1 Every day over one million people are treated successfully by National Health Service (NHS) acute, ambulance and mental health trusts. However, healthcare relies on a range of complex interactions of people, skills, technologies and drugs, and sometimes things do go wrong. For most countries, patient safety is now the key issue in healthcare quality and risk management. The Department of Health (the Department) estimates that one in ten patients admitted to NHS hospitals will be unintentionally harmed, a rate similar to other developed countries. Around 50 per cent of these patient safety incidentsa could have been avoided, if only lessons from previous incidents had been learned. 2 There are numerous stakeholders with a role in keeping patients safe in the NHS, many of whom require trusts to report details of patient safety incidents and near misses to them (Figure 2). However, a number of previous National Audit Office reports have highlighted concerns that the NHS has limited information on the extent and impact of clinical and non-clinical incidents and trusts need to learn from these incidents and share good practice across the NHS more effectively (Appendix 1). 3 In 2000, the Chief Medical Officer’s report An organisation with a memory 1 , identified that the key barriers to reducing the number of patient safety incidents were an organisational culture that inhibited reporting and the lack of a cohesive national system for identifying and sharing lessons learnt. 4 In response, the Department published Building a safer NHS for patients3 detailing plans and a timetable for promoting patient safety. The goal was to encourage improvements in reporting and learning through the development of a new mandatory national reporting scheme for patient safety incidents and near misses. Central to the plan was establishing the National Patient Safety Agency to improve patient safety by reducing the risk of harm through error. The National Patient Safety Agency was expected to: collect and analyse information; assimilate other safety-related information from a variety of existing reporting systems; learn lessons and produce solutions. 5 We therefore examined whether the NHS has been successful in improving the patient safety culture, encouraging reporting and learning from patient safety incidents. Key parts of our approach were a census of 267 NHS acute, ambulance and mental health trusts in Autumn 2004, followed by a re-survey in August 2005 and an omnibus survey of patients (Appendix 2). We also reviewed practices in other industries (Appendix 3) and international healthcare systems (Appendix 4), and the National Patient Safety Agency’s progress in developing its National Reporting and Learning System (Appendix 5) and other related activities (Appendix 6). 6 An organisation with a memory1 was an important milestone in the NHS’s patient safety agenda and marked the drive to improve reporting and learning. At the local level the vast majority of trusts have developed a predominantly open and fair reporting culture but with pockets of blame and scope to improve their strategies for sharing good practice. Indeed in our re-survey we found that local performance had continued to improve with more trusts reporting having an open and fair reporting culture, more trusts with open reporting systems and improvements in perceptions of the levels of under-reporting. At the national level, progress on developing the national reporting system for learning has been slower than set out in the Department’s strategy of 2001 3 and there is a need to improve evaluation and sharing of lessons and solutions by all organisations with a stake in patient safety. There is also no clear system for monitoring that lessons are learned at the local level. Specifically: a The safety culture within trusts is improving, driven largely by the Department’s clinical governance initiative 4 and the development of more effective risk management systems in response to incentives under initiatives such as the NHS Litigation Authority’s Clinical Negligence Scheme for Trusts (Appendix 7). However, trusts are still predominantly reactive in their response to patient safety issues and parts of some organisations still operate a blame culture. b All trusts have established effective reporting systems at the local level, although under-reporting remains a problem within some groups of staff, types of incidents and near misses. The National Patient Safety Agency did not develop and roll out the National Reporting and Learning System by December 2002 as originally envisaged. All trusts were linked to the system by 31 December 2004. By August 2005, at least 35 trusts still had not submitted any data to the National Reporting and Learning System. c Most trusts pointed to specific improvements derived from lessons learnt from their local incident reporting systems, but these are still not widely promulgated, either within or between trusts. The National Patient Safety Agency has provided only limited feedback to trusts of evidence-based solutions or actions derived from the national reporting system. It published its first feedback report from the Patient Safety Observatory in July 2005

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy

Frameworks for Evaluating Qualitative and Quantitative Information on Adverse Drug Events throughout Development through to Marketing

Significant public health issues caused by adverse drug reactions in the post-marketing phase, such as birth defects by thalidomide, have been well described. Unfortunately, subjects in clinical trials cannot completely avoid severe harm during drug development. TGN1412 in 2006 and BIA 10-2474 in 2016 were withdrawn from development due to severe adverse reactions in first-into-man studies. Thus, monitoring drug safety is important throughout all phases of development. In twenty-first century, minimizing drug development cost and time is a challenge for pharmaceutical companies. When a drug is approved with a smaller size and fewer number of clinical trials, pharmacovigilance and benefit-risk evaluation after marketing need to be sufficiently performed. Underpinned by understanding of the traditional methods of evaluating adverse drug reactions, new developments in IT and computing might well help us to detect drug safety signals earlier, enabling prompt intervention for protecting the rights of subjects and public health