Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

Reducing Medication Errors in the Acute Care In-Patient Setting: An Integrative Review

Promoting a culture of safety in healthcare organizations has become a necessary goal to ensure that patients are safe, well cared for, and satisfied with the services they receive. One of the areas recognized as a major safety concern across hospitals in the United States and abroad are medication errors, which continue to occur at a staggering rate. This integrative review seeks to serve two purposes to combat this pandemic problem. First, the project will attempt to determine if an appropriate intervention or strategic initiative exists that can reduce medications errors for adult patients on an acute care patient unit in an inpatient hospital setting. Second, will be to disseminate and implement the identified cluster of interventions at a healthcare organization in central Virginia, and follow the data trends to determine its effectiveness

Leveraging Knowledge-Based Approaches to Promote Antiretroviral Toxicity Monitoring in Underserved Settings

As access and use of antiretroviral therapy continue to increase, the need to improve antiretroviral toxicity monitoring becomes more critical. This is particularly so in underserved settings, where patterns of antiretroviral toxicities possibly alter the need for and frequency of antiretroviral toxicity monitoring. However, barriers such as few skilled healthcare providers and poor infrastructure make antiretroviral toxicity monitoring in underserved settings difficult. The purpose of this dissertation was to investigate how standard clinical guidelines, knowledge-based clinical decision support, and task delegation could be leveraged to overcome barriers to antiretroviral toxicity monitoring in underserved settings. The strategy adopted in this dissertation was guided by the Design Science Research Methodology that emphasizes the generation of scientific knowledge through building novel artifacts. Two qualitative descriptive studies were conducted to characterize the contextual factors associated with antiretroviral toxicity monitoring in underserved settings. Supported by the findings from these studies, a knowledge-based software application prototype that implements clinical practice guidelines for antiretroviral toxicity monitoring was developed. Next, a quantitative validation study was used to evaluate the structure and behavior of the prototype’s knowledge base. Lastly, a quantitative usability study was conducted to assess lay health worker perceptions of the satisfaction and mental effort associated with the use of checklists generated by the prototype. This dissertation research produced empirical evidence about the broad motives and strategies for promoting medication adherence, safety, and effectiveness in underserved settings. It also identified barriers and facilitators of antiretroviral toxicity monitoring within ambulatory HIV care workflows in underserved settings. Additionally, it provided evidence about the extent to which antiretroviral toxicity domain knowledge could be implemented in a knowledge-based application for supporting point-of-care antiretroviral toxicity monitoring. Lastly, the research provided previously unavailable empirical evidence about the perceptions of lay peer health workers on the use of checklists for the documentation of antiretroviral toxicities

Electronic Health Records: Delivering the Right Information to the Right Health Care Providers at the Right Time

In 1993 I wrote "Communication and information management consume as much as 40 percent of all inpatient costs, yet errors still occur at an unacceptable rate. The Institute of medicine has suggested that electronic medical records (EMRs) will help lower health care costs, maintain quality of care, and provide physicians with better information" (Tierney et al. 1993, 379). Nearly 20 years later I'm here to tell you how far we've come toward implementing EHRs nationwide, and what we've learned from our experience at the Regenstrief Institute in Indiana University. Most of us consider health care to be a service business, because we think in terms of a patient who goes to the doctor to get some thing: advice, medication, devices, surgery, or physical therapy. I'm going to argue that what patients really get, and health care practitioners really provide, is information. Ninety-eight percent of what we who practice medicine do is not the end result, the end service, but the overall process of getting there.electronic medical records, EMRs, EHRs

Mycobacterium W immunotherapy for treating pulmonary tuberculosis : a systematic review

Includes bibliographical references.Tuberculosis (TB) remains a major health problem in the developing world, accounting for approximately 2 million deaths per year. The search for appropriate and applicable therapies to reduce the burden of TB is essential. Mycobacterium w (M w) is a heat-killed immune-modulating vaccine designed to attenuate the effects of TB infection and reduce the time to sputum negativity, thereby improving cure rates and decreasing transmission rates

Adoptive cell transfer: examining the potential of a T cell-mediated therapy for metastatic melanoma

Adoptive cell transfer techniques identify and isolate patient anti-tumor lymphocytes in vitro followed by ex vivo expansion of these tumor specific T cells. Identification and isolation of lymphocytes from patient tumors allows for the selection of anti-tumor lymphocytes that are highly specific for individual tumor antigens. Furthermore, recombinant technology allows for engineering of chimeric antigen receptors (CARs) which allow these T cells to target multiple tumor antigens. Techniques involving ex vivo growth lead to a 1,000- to 5,000-fold increase in numbers of lymphocytes. Cultured lymphocytes can then be infused via IV and growth maintained with administration of exogenous IL-2. Cancer patients are then monitored for both immunological activity as well as any adverse cytokine reactions. We looked at several trial studies for the application of adoptive cell transfer in metastatic melanoma compare the efficacy of the regimen to other established melanoma treatments. Adoptive transfer has proven to be effective for patients with late stage melanoma, however, the aim of this study was to examine some of the challenges in creating an effective standard protocol for adaptation in clinical settings, including difficulty in obtaining significant cell populations from tumors, challenges in the proliferation of these tumor-infiltrating lymphocytes (TIL) and determination of antigen-specificity, i.e. facilitation of a simplified and quicker approach to the therapy

The impact of care coordination on community pharmacist-delivered medication therapy management

Background: Care coordination is imperative to successful patient outcomes. However, community pharmacists are commonly excluded from health information exchange during care coordination. One of the ways pharmacists deliver care, through medication therapy management (MTM), could be optimized if pharmacists engaged in care coordination through review of unedited patient medical records in preparation for a section of the MTM, the comprehensive medication review (CMR).^ Methods: This was a non-blinded randomized controlled trial undertaken within the Medication Safety Research network of Indiana, also known as RxSafeNet. RxSafeNet is a community pharmacy practice based research network. Pharmacists were randomized to deliver CMR’s to adult patients under usual care, or with a care coordination intervention. The intervention consisted of soliciting the patient-identified primary care provider-held medical records of the last six months. Medication related problems (MRPs) identified and omissions in preventative care identified were recorded for each CMR delivered. Additionally, pharmacists were surveyed over their thoughts and opinions regarding utilizing medical records.^ Results: Thirty seven patients were seen for CMR appointments. Intervention pharmacists identified more MRP’s than usual care pharmacists. The intervention, while controlling for predictor variables included in a multiple linear regression model, had an adjusted R2= 0.511; p=0.05. Intervention pharmacists identified more omissions in preventative care (adjusted R2= 0.136; p=0.027).^ Intervention pharmacists were more likely to agree they were confident they identified all of the patient’s MRPs (47.1% vs. 15.8%), but neither group was more likely than the other to believe they had resolved all MRPs (41.2% vs. 42.1%). Lastly, intervention pharmacists agreed 100% of the time that the patient’s health history helped them complete a better CMR as compared with only 69% of usual care pharmacists.^ Conclusion: Community pharmacists identify more MRPs and omissions in preventative care when they engage in care coordination by reviewing the patient’s PCP’s unedited medical record in preparation for a CMR

The system of aseptic preparation of intravenous drugs in clinical care settings

Abstract A review of the literature on blood stream infections caused by contaminated intravenous infusates which are prepared in clinical care settings found that this common nursing procedure poses at times a significant and life-threatening risk to patients. The guidance and regulations surrounding the preparation of intravenous drugs in clinical care settings suggests that this procedure is extremely complex and poses many different potential hazards to patients. This thesis set out to determine how the infection risks are being addressed in practice by asking the questions: ‘What is the system of intravenous drug preparation in clinical care settings in NHS Scotland?’ and, ‘How does it work in practice?’ Several data sources were utilised: six locations, in specialities where the literature identified significant outbreaks had occurred, were examined for potential contamination risk. Observations (78) of infusate preparations were undertaken and, where available, written procedures were compared with observed practices. Finally, analyses were made of 71 questionnaires, completed by the nurses who prepare intravenous drugs, regarding their opinions of the procedures’ safety and when they perform redundancy checks. The conclusion of this study is that the system of preparing intravenous drugs in clinical care settings by nurses is, as a consequence of potential infusate contamination, error-prone and unreliable. The reasons for this conclusion are now detailed. o Due to a lack of mandatory environmental standards, and the provision of poor environments, there is a risk of infusate contamination from environmental sources and consequently, a risk to patients of infusate-related blood stream infections (IR-BSI). o Some in use equipment poses contamination risks to patients’ infusates. Equipment that could reduce the contamination risk is not always available and in some instances such safety-enhancing equipment has been removed. o There are no complete written procedures which mirror what is done in practice. At present, from a human-factors perspective, it is not easy for the nurse to do the right thing, or to be sure exactly what is the right thing to do. o The procedure, in practice, has the required elements of an aseptic procedure, but the execution of the procedure is more often not performed aseptically. o The procedure of intravenous drug preparation as observed is mainly an interrupted aseptic procedure and as such the recommencement of the aseptic procedure requires repeated hand hygiene. o The nurses’ opinions of safety vary, as did their assessment of the infection risk to their patients, but it is clear that intravenous drug preparation is not a much-loved nursing procedure and some nurses find it very stressful. o There is no asepsis quality control built into the system. Aseptic steps are the least likely to be performed as a redundancy check compared to the mandatory checks of ‘right patient, right drug and right dose’. o The information available to the nurses, from the drug companies, from the makers of equipment and from national agencies does not identify with sufficient clarity the infection risks, or detail how to negate them. Suggestions for improvement to the six procedures and environments are clear once the procedure steps are colour-coded as either aseptic or non-aseptic; validity testing of these improvements is however, still needed. The systems’ vulnerabilities observed in this research appear to stem from a chain of external influences including an underestimation of the problem size and the actions needed to prevent it in evidence-based guidelines and mandatory guidance. This leads to poor recognition of the risk of IR-BSI in clinical practice. The problem of infusate contamination causing IR-BSIs is further compounded by the fact that it is not caused by a single organism and does not always present as a disease in real time, that is, over the lifetime of the infusion. As a consequence, this presents surveillance difficulties in terms of definitions, data collection and analysis. Finally, although the diagnosis of a blood stream infection for an individual patient remains relatively easy, it is not easy to recognise a contaminated infusate as the origin of the problem. All these challenges make both the recognition of the problem and agreement on prevention strategies, extremely challenging. In summary, the main conclusion of this thesis is that the preparation of infusates in clinical care settings, which occurs approximately 3,000,000 times a year in NHSScotland, is from an aseptic perspective, error-prone and unreliable. Recommendations to optimise patient safety include, changing the procedure locally and, with the utmost urgency, the production of minimum environmental standards. The results of this study are relevant to all hospitals in Scotland and throughout the United Kingdom where the current regulations apply and similar procedures are performed