Is It Time for the Customizable Infobutton?

Infobuttons are intended to provide links to context-sensitive information in online resources to support clinical decision making. In this issue, we discuss challenges that impact the maximal effective use of Infobuttons. We also suggest methods to facilitate the role of Infobuttons as a tool to support optimal use of medications.The medication use process can be negatively impacted by inappropriate patient selection for drug therapy, nonscientific ordering behaviors, incorrect preparation procedures, inaccurate administration, and poor follow-up procedures. The process is further complicated when patients demand therapeutic interventions and providers believe that medication use is appropriate, even when there is no scientific evidence to support these treatment decisions. Access to information can aid clinical decision making and avoid the problems affecting the medication use process.HL7 International Context-Aware Information Retrieval standard (the HL7 “Infobutton” standard) has been widely adopted since 2007. Infobuttons are decision support tools that provide links within electronic medical record (EMR) systems to online information. Many practitioners are discovering that the Infobutton is defaulting to a static, tertiary reference monograph that is intended to guide decisions for all who participate in the medication use process. But decision support information is seldom a one-size-fits-all proposition. We believe that the Infobutton should be customizable for an individual health system’s use.Every guideline that is distributed to health systems gets vetted by a clinical review committee prior to being placed online for general use. We worked on a project where such a guideline was distributed to 128 hospitals and nearly every hospital found something to tweak in the guideline. We believe that Infobuttons could appropriately publish checklisted, evidence-based decision support to prompt both experienced and naïve users throughout the medication use process. Infobutton use could also lead to more updates, as feedback is gained from the use of specific medications and problems emerge in actual practice.The Agency for Healthcare Research and Quality considers a checklist to be “an algorithmic listing of actions to be performed in a clinical setting” with the intended goal being “to ensure that no step will be forgotten. Although a seemingly simple intervention, checklists have a sound theoretical basis in principles of human factors engineering and have played a major role in some of the most significant successes achieved in the patient safety movement.”¹ Patient safety movements continue to promote the benefit of checklist-based approaches. Although mistakes can happen, slips are very preventable with the appropriate use of this tool.Clinicians are pressed for time due to the emergent conditions of their patients and their total patient loads. Under this pressure, they must make decisions about the safe use of drug interventions for which they may have little or no prior experience. This situation is not exclusive to physicians; it occurs across the medication use process. Therefore, the ideal Infobutton should allow systematic access and concurrently allow users to drill down to the precise nugget of information that is needed. We recommend navigation options that include links to these nuggets but also provide the ability to expand and collapse sections of extensive monographs to aid the rapid access to the desired decision support.When calculations about medications are required, it would be ideal to have patient demographics and lab values accessible and integrated to the Infobutton so that values can be verified and calculations can be made from prepopulated data. When integration is not available, data entry should be supported through checkboxes, radio buttons, pull-down lists, and controlled keyboard/touchscreen inputs. Instructions that require preparation procedures for drug products should utilize video demonstrations or illustrated steps that demonstrate how to achieve optimal results. Infobuttons should be designed to prevent errors by requiring users to start with a checklist that has been cleared automatically from any previous user. Additionally, print capabilities and download capabilities should make the Infobutton materials available for in-service education when desired.The use of checklists and other decision-support tools is not without controversy. Many clinicians see them as time robbers and yet another distraction to their thought processes. This viewpoint may indicate the need for a shift in organizational culture to put safety first, employing procedures, policies, and tools to enable a unified focus. A shift to a culture of safety often advances the use of decision-support tools. It may be necessary to hold providers accountable when they fail to use these tools when working with either new medications or medications that have known safety implications and have created problems in the medication use process. The ability for an individual health system to customize decision-support tools may help providers feel that they have ownership of the approach and may undercut their criticism that guidelines promote cookie-cutter medicine. Each Infobutton would be available on every screen in the EHR any time a medication consideration is being addressed. Thus, no provider would have to pull out a smart phone or go to another program outside of the EHR to access information.We found out through an advisory board that many drug products are associated with expert users in health systems. A further customization of an Infobutton would be to add a list of these experts and their contact information that would be available for clinicians when they experience difficulty with the use of these products or procedures. Most pharmaceutical companies also provide additional support in the form of 24-hour medical information hotlines and product-specific Web sites. We believe that the best customizable Infobutton would have a controlled editing environment that would allow US Food and Drug Administration–approved content to be displayed initially and would have the capacity for additional helpful information to be added through editing of the distributed information button content. The restoration of the original text back to the distributed document would also be a desirable feature for this content.We are excited that the opportunity for the receipt of just-in-time information continues to be enhanced. Although we know that errors and mistakes will occur, time-proven methods such as checklists can make the medication use process increasingly safe. We encourage your comments and questions to either Bill at ude.nrubua@gbeklef or Brent at ude.nrubua@nerbxof. We would enjoy continuing this conversation.     

Risk of Hepatitis B for Travelers: Is Vaccination for All Travelers Really Necessary?

Objectives.  Behavioral studies in travelers suggest that 33% to 76% of all travelers to hepatitis B virus (HBV)–endemic countries are at risk for HBV infection. We study the incidence and risk factors for HBV infection in travelers.
Methods.  Retrospective analysis of the characteristics and risk factors of all reported acute HBV patients in Amsterdam, the Netherlands, from January 1, 1992, until December 31, 2003.
Results.  The estimated incidence in travelers from Amsterdam to HBV-endemic countries is 4.5/100,000 travelers. Two thirds of these patients were immigrants who lived in Amsterdam and who had visited their friends and relatives in their country of origin. In 12 years, only three Dutch short-term tourists contracted HBV while traveling, all by heterosexual contacts.
Conclusions.  Dutch tourists who travel to HBV-endemic countries run a very low risk of contracting HBV. Vaccination of short-term Dutch tourists is not necessary. Immigrants run a higher risk irrespective of travel or duration of travel. This group should be advised vaccination.     

Diabetes and Cardiovascular Risk: Are Dipeptidyl Peptidase-4 Inhibitors Beneficial?

Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with diabetes. Whereas the link between glycemic control and reducing microvascular disease is firmly established, the evidence for macrovascular risk reduction remains unclear. Despite a host of available drugs for lowering serum glucose, none to date have been shown to substantially reduce CV risk and some have been associated with adverse effects. Recent trials have examined the CV effects of the dipeptidyl peptidase 4 (DPP-4) inhibitors or “gliptins.”Type 2 diabetes affects an estimated 25.8 million individuals in the United States.¹ Almost 2 million new cases were diagnosed in 2010 among adults 20 years of age and older. Data from the US Health and Nutritional Examination Survey (NHANES) indicate that the prevalence of diabetes increased dramatically from an estimated 6.2% for 1988-1994 to an estimated 9.9% for 2005-2010.²Diabetes is associated with accelerated atherosclerosis and is often considered to be a “coronary equivalent.” The overall risks of cardiovascular disease (CVD) and stroke are 2 to 4 times higher in individuals with diabetes compared to nondiabetics.¹ Despite the availability of numerous therapeutic agents with proven efficacy for lowering blood glucose, none have been shown to substantially reduce CV risk. Even more concerning is the fact that a number of these drugs have been associated with detrimental effects. For example, thiazolidinediones including rosiglitazone and pioglitazone, have been associated with an increased risk of heart failure resulting in a black box warning.³ Rosiglitazone has previously been associated with a potential increased risk of myocardial infarction and, although many of the restrictions on its use have now been removed, the US Food and Drug Administration (FDA) continues to monitor.^4,5Because CVD is a leading cause of death among diabetics, the development of additional antihyperglycemic drugs has provided an opportunity to determine the relative CV risk associated with these drugs. With this in mind, the FDA issued a 2008 guidance that manufacturers of new diabetes drugs should conduct studies to evaluate CV safety.⁶ The newest class of glucose-lowering drugs to undertake this assessment of CV risk is the dipeptidyl peptidase 4 (DPP-4) inhibitors. This article will discuss the findings from 2 recent clinical trials assessing the CV risk of these agents and the ongoing issues related to preventing macrovascular complications in patients with diabetes.     

Cardiovascular diseases--bulk producers for prevention?

An unfavourable constellation of plasma lipids, e.g., a high triglyceride concentration in combination with a low HDL cholesterol concentration, is a relevant risk factor for the development of arteriosclerosis and coronary heart disease. Plasma lipids may be favourably influenced by bulk producers, in particular by plantago seed (psyllii semen). Several mechanisms of action are involved in this effect.     

Risk and protection factors for different intensities of adolescent substance use: when does the Prevention Paradox apply?

The 'Prevention Paradox' applies when low-risk individuals in a population contribute the most cases of a condition or problem behaviour by virtue of their being in the majority, thereby recommending a universal or whole of population approach to prevention. The applicability of a universal as opposed to a targeted high-risk approach to the prevention of youth substance use was examined in two studies of children and adolescents conducted in Victoria, Australia. These studies were reanalysed by recombining developmental, social and individual measures to form cumulative risk indices for substance use. In Study 1, a cross-sectional survey of students, most regular tobacco, alcohol and cannabis use by 15/16-year-olds occurred in the moderate and low-risk groups, recommending a universal prevention strategy. However, the majority of illicit drug use occurred in the highest-risk group (top 15%). Furthermore, in younger age groups both legal and illegal drug use was concentrated mainly in the highest risk group. Study 2 used data from a major longitudinal study where risk factors at around age 11/12 years were used to predict substance use at age 17/18 years. Most students who admitted involvement in frequent smoking, heavy drinking and, although to a lesser degree, cannabis were classified as low or average risk. It is concluded that universal prevention strategies are needed for late adolescent alcohol, tobacco and cannabis use and more targeted strategies for addressing harm related to early age drug use, frequent cannabis use and illegal drug use.     

A Wakeup Call to the Prevention Field: Are Prevention Programs for Substance Use Effective for Girls?

Substance misuse in adolescent girls has increased dramatically since 1992. This article reviews trends in use rates and etiological theories tested by gender that suggest that family protective factors have more influence on girls. Next, a literature review reveals that few prevention programs have published their outcomes by gender or developed gender-specific programs. Nationwide community coalition results found positive effects on boys but increased drug use in young girls. The most effective programs are family focused targeting family bonding, supervision, and communication. Recent gender-specific prevention programs with positive results address stress, depression, social assertiveness, and body image. The authors recommend additional research testing programs by gender and also gender-specific versus generic versions of evidence-based programs to determine how to improve prevention program effectiveness for girls.     

High-Dose Omega-3 Fatty Acids in Cardiovascular Prevention: Finally Living Up to Their Potential?

American Journal of Cardiovascular Drugs - Despite the widespread use of statins in the setting of high cardiovascular risk, many patients continue to experience clinical events. This highlights...     

Identifying High School Students “At Risk” for Substance Use and Other Behavioral Problems: Implications for Prevention

Attendance and grade point average (GPA) data are universally maintained in school records and can potentially aid in identifying students with concealed behavioral problems, such as substance use. Researchers evaluated attendance (truancy) and GPA as a means to identify high school students at risk for substance use, suicide behaviors, and delinquency in 10 high schools in San Antonio, Texas, and San Francisco, California, during the spring and fall of 2002. A screening protocol identified students as “high risk” if (1) in the top quartile for absences and below the median GPA or (2) teacher referred. Survey responses of 930 high-risk students were compared with those from a random sample of 393 “typical” students not meeting the protocol. Bivariate and multivariate analyses assessed associations between the screening protocol variables and demographics, risk and protective factors, and problem outcomes. The individual contribution of each of the variables was also assessed. Students identified as high risk were significantly more likely than typical students to use cigarettes, alcohol, and marijuana, evidence suicide risk factors, and engage in delinquent behavior. Norms varied between the two districts; nevertheless, high-risk students showed consistent differences in risk and protective factors, as well as problem behaviors, compared with typical students. Because of site differences in data collection and teacher participation, the comprehensive protocol is recommended, rather than individual indicators alone (e.g., truancy). Strengths of the screening protocol are the ready availability of school record data, the ease of use of the adapted protocol, and the option of including teacher referral. More research is recommended to test the generalizability of the protocol and to ensure that there are no unintended negative effects associated with identification of students as high risk.     

Does It Make Sense To Develop New Centrally Acting Cardiovascular Drugs?

1. The autonomic nervous system plays a pivotal role in modulating all the components of the cardiovascular regulation. Therefore, one can assume that drugs targeting this system may be useful in the management of several cardiovascular diseases. 2. Drugs acting on central nervous system centres seem to be modulators rather than blockers; as such, they are expected to preserve the contraregulatory processes and to generate only a few side effects. 3. Because the sympathetic nervous system is largely involved in the regulation of vasomotor tone, centrally acting antihypertensive drugs were developed first. 4. Recently, new leader compounds selective for non- adrenergic imidazoline recepetors have been synthetized. Although such drugs have no capacity to activate alpha2-adrenoceptors, they have been proven to be hypotensive. These drugs are expected to be even better tolerated than the currently available centrally active drugs. They may also have additional beneficial effects. 5. Here, the experimental evidence suggesting that such drugs may be useful in the management of some cardiac arrhythmias and/or left ventricular dysfunction will be reviewed.     

What Is Diversion of Supervised Buprenorphine and How Common Is It?

ABSTRACT

This study aimed to identify the practices of community pharmacists regarding the provision of buprenorphine for opioid dependence and explore behaviors pharmacists considered indicative of buprenorphine diversion. A cross-sectional survey of 669 community pharmacists authorized to dispense buprenorphine or methadone was conducted in New South Wales and Victoria, Australia. There was wide variation between pharmacies in the level of supervision provided during supervised buprenorphine dosing and a lack of clarity between pharmacists regarding what behaviors are examples of buprenorphine diversion. Compared to New South Wales, a higher proportion of Victorian pharmacists detected 1 or more episodes of buprenorphine diversion in the past year (65% vs. 28%; p < .001) and in the past month (20% vs. 7%; p < .001). Detection of buprenorphine diversion was associated with the administration of crushed tablets (odds ratio = 2.77), broken tablets (odds ratio = 2.69), and having more buprenorphine clients (odds ratio = 1.24). Future research investigating the prevalence of buprenorphine diversion should include a clear definition of what behaviors constitute diversion.     

Is It the Twilight of BACE1 Inhibitors?

β-secretase (BACE1) has been regarded as a prime target for the development of amyloid beta (Aβ) lowering drugs in the therapy of Alzheimer´s disease (AD). Although the enzyme was discovered in 1991 and helped to formulate the Aβ hypothesis as one of the very important features of AD etiopathogenesis, progress in AD treatment utilizing BACE1 inhibitors has remained limited. Moreover, in the last years, major pharmaceutical companies have discontinued clinical trials of five BACE1 inhibitors that had been strongly perceived as prospective. In our review, the Aβ hypothesis, the enzyme, its functions, and selected substrates are described. BACE1 inhibitors are classified into four generations. Those that underwent clinical trials displayed adverse effects, including weight loss, skin rashes, worsening of neuropsychiatric symptoms, etc. Some inhibitors could not establish a statistically significant risk-benefit ratio, or even scored worse than placebo. We still believe that drugs targeting BACE1 may still hide some potential, but a different approach to BACE1 inhibition or a shift of focus to modulation of its trafficking and/or post-translational modification should now be followed.     

Negative Prognostic Effect of Baseline Antipsychotic Exposure in Clinical High Risk for Psychosis (CHR-P): Is Pre-Test Risk Enrichment the Hidden Culprit?

IntroductionSample enrichment is a key factor in contemporary early-detection strategies aimed at the identification of help-seekers at increased risk of imminent transition to psychosis. We undertook a meta-analytic investigation to ascertain the role of sample enrichment in the recently highlighted negative prognostic effect of baseline antipsychotic (AP) exposure in clinical high-risk (CHR-P) of psychosis individuals.MethodsSystematic review and meta-analysis of all published studies on CHR-P were identified according to a validated diagnostic procedure. The outcome was the proportion of transition to psychosis, which was calculated according to the Freeman‐Tukey double arcsine transformation.ResultsThirty-three eligible studies were identified, including 16 samples with details on AP exposure at baseline and 17 samples with baseline AP exposure as exclusion criterion for enrollment. Those with baseline exposure to AP (n = 395) had higher transition rates (29.9%; 95% CI: 25.1%–34.8%) than those without baseline exposure to AP in the same study (n = 1289; 17.2%; 15.1%–19.4%) and those coming from samples that did not include people who were exposed to AP at baseline (n = 2073; 16.2%; 14.6%–17.8%; P < .05 in both the fixed-effects and the random-effects models). Heterogeneity within studies was substantial, with values above 75% in all comparisons.ConclusionsSample enrichment is not a plausible explanation for the higher risk of transition to psychosis of CHR-P individuals who were already exposed to AP at the enrollment in specialized early-detection programs. Baseline exposure to AP at CHR-P assessment is a major index of enhanced, imminent risk of psychosis.     

Micelle-Associated Protein in Epoetin Formulations: A Risk Factor for Immunogenicity?

PURPOSE: An upsurge of pure red cell aplasia (PRCA) cases associated with subcutaneous treatment with epoetin alpha has been reported. A formulation change introduced in 1998 is suspected to be the reason for the induction of antibodies that also neutralize the native protein. The aim of this study was to detect the mechanism by which the new formulation may induce these antibodies. METHODS: Formulations of epoetin were subjected to gel permeation chromatography with UV detection, and the fractions were analyzed by an immunoassay for the presence of epoetin. RESULTS: The chromatograms showed that Eprex/Erypo contained micelles of Tween 80. A minute amount of epoetin (0.008-0.033% of the total epoetin content) coeluted with the micelles, as evidenced by ELISA. When 0.03% (w/v) Tween 80, corresponding to the concentration in the formulation, was added to the elution medium, the percentage of epoetin eluting before the main peak was 0.68%. CONCLUSIONS: Eprex/Erypo contains micelle-associated epoetin, which may be a risk factor for the development of antibodies against epoetin.