A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

Ability of online drug databases to assist in clinical decision-making with infectious disease therapies

<p>Abstract</p> <p>Background</p> <p>Infectious disease (ID) is a dynamic field with new guidelines being adopted at a rapid rate. Clinical decision support tools (CDSTs) have proven beneficial in selecting treatment options to improve outcomes. However, there is a dearth of information on the abilities of CDSTs, such as drug information databases. This study evaluated online drug information databases when answering infectious disease-specific queries.</p> <p>Methods</p> <p>Eight subscription drug information databases: American Hospital Formulary Service Drug Information (AHFS), Clinical Pharmacology (CP), Epocrates Online Premium (EOP), Facts & Comparisons 4.0 Online (FC), Lexi-Comp (LC), Lexi-Comp with AHFS (LC-AHFS), Micromedex (MM), and PEPID PDC (PPDC) and six freely accessible: DailyMed (DM), DIOne (DIO), Epocrates Online Free (EOF), Internet Drug Index (IDI), Johns Hopkins ABX Guide (JHAG), and Medscape Drug Reference (MDR) were evaluated for their scope (presence of an answer) and completeness (on a 3-point scale) in answering 147 infectious disease-specific questions. Questions were divided among five classifications: antibacterial, antiviral, antifungal, antiparasitic, and vaccination/immunization. Classifications were further divided into categories (e.g., dosage, administration, emerging resistance, synergy, and spectrum of activity). Databases were ranked based on scope and completeness scores. ANOVA and Chi-square were used to determine differences between individual databases and between subscription and free databases.</p> <p>Results</p> <p>Scope scores revealed three discrete tiers of database performance: Tier 1 (82-77%), Tier 2 (73-65%) and Tier 3 (56-41%) which were significantly different from each other (p < 0.05). The top tier performers: MM (82%), MDR (81%), LC-AHFS (81%), AHFS (78%), and CP (77%) answered significantly more questions compared to other databases (p < 0.05). Top databases for completeness were: MM (97%), DM (96%), IDI (95%), and MDR (95%). Subscription databases performed better than free databases in all categories (p = 0.03). Databases suffered from 37 erroneous answers for an overall error rate of 1.8%.</p> <p>Conclusion</p> <p>Drug information databases used in ID practice as CDSTs can be valuable resources. MM, MDR, LC-AHFS, AHFS, and CP were shown to be superior in their scope and completeness of information, and MM, AHFS, and MDR provided no erroneous answers. There is room for improvement in all evaluated databases.</p

Primary care medication safety surveillance with integrated primary and secondary care electronic health records: a cross-sectional study

Introduction: The extent of preventable medication-related hospital admissions and medication-related issues in primary care is significant enough to justify developing decision support systems for medication safety surveillance. The prerequisite for such systems is defining a relevant set of medication safety-related indicators and understanding the influence of both patient and general practice characteristics on medication prescribing and monitoring. Objective: The aim of the study was to investigate the feasibility of linked primary and secondary care electronic health record data for surveillance of medication safety, examining not only prescribing but also monitoring, and associations with patient- and general practice-level characteristics. Methods: A cross-sectional study was conducted using linked records of patients served by one hospital and over 50 general practices in Salford, UK. Statistical analysis consisted of mixed-effects logistic models, relating prescribing safety indicators to potential determinants. Results: The overall prevalence (proportion of patients with at least one medication safety hazard) was 5.45 % for prescribing indicators and 7.65 % for monitoring indicators. Older patients and those on multiple medications were at higher risk of prescribing hazards, but at lower risk of missed monitoring. The odds of missed monitoring among all patients were 25 % less for males, 50 % less for patients in practices that provide general practitioner training, and threefold higher in practices serving the most deprived compared with the least deprived areas. Practices with more prescribing hazards did not tend to show more monitoring issues. Conclusions:Systematic collection, collation, and analysis of linked primary and secondary care records produce plausible and useful information about medication safety for a health system. Medication safety surveillance systems should pay close attention to patient age and polypharmacy with respect to both prescribing and monitoring failures; treat prescribing and monitoring as different statistical processes, rather than a combined measure of prescribing safety; and audit the socio-economic equity of missed monitoring

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

A descriptive exploratory study of how admissions caused by medication-related harm are documented within inpatients' medical records.

BACKGROUND: Adverse drug reactions, poor patient adherence and errors, here collectively referred to as medication-related harm (MRH), cause around 2.7-8.0% of UK hospital admissions. Communication gaps between successive healthcare providers exist, but little is known about how MRH is recorded in inpatients' medical records. We describe the presence and quality of MRH documentation for patients admitted to a London teaching hospital due to MRH. Additionally, the international classification of disease 10th revision (ICD-10) codes attributed to confirmed MRH-related admissions were studied to explore appropriateness of their use to identify these patients. METHODS: Clinical pharmacists working on an admissions ward in a UK hospital identified patients admitted due to suspected MRH. Six different data sources in each patient's medical record, including the discharge summary, were subsequently examined for MRH-related information. Each data source was examined for statements describing the MRH: symptom and diagnosis, identification of the causative agent, and a statement of the action taken or considered. Statements were categorised as 'explicit' if unambiguous or 'implicit' if open to interpretation. ICD-10 codes attributed to confirmed MRH cases were recorded. RESULTS: Eighty-four patients were identified over 141 data collection days; 75 met our inclusion criteria. MRH documentation was generally present (855 of 1307 statements were identified; 65%), and usually explicit (705 of 855; 82%). The causative agent had the lowest proportion of explicit statements (139 of 201 statements were explicit; 69%). For two (3%) discharged patients, the causal agent was documented in their paper medical record but not on the discharge summary. Of 64 patients with a confirmed MRH diagnosis at discharge, only six (9%) had a MRH-related ICD-10 code. CONCLUSIONS: Availability of information in the paper medical record needs improving and communication of MRH-related information could be enhanced by using explicit statements and documenting reasons for changing medications. ICD-10 codes underestimate the true occurrence of MRH

Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes

Adverse drug reactions (ADRs) are a major cause of hospital admissions, but recent data on the incidence and clinical characteristics of ADRs which occur following hospital admission, are lacking. Patients admitted to twelve wards over a six-month period in 2005 were assessed for ADRs throughout their admission. Suspected ADRs were recorded and analysed for causality, severity and avoidability and whether they increased the length of stay. Multivariable analysis was undertaken to identify the risk factors for ADRs. The 5% significance level was used when assessing factors for inclusion in multivariable models. Out of the 3695 patient episodes assessed for ADRs, 545 (14.7%, 95% CI 13.6–15.9%) experienced one or more ADRs. Half of ADRs were definitely or possibly avoidable. The patients experiencing ADRs were more likely to be older, female, taking a larger number of medicines, and had a longer length of stay than those without ADRs. However, the only significant predictor of ADRs, from the multivariable analysis of a representative sample of patients, was the number of medicines taken by the patient with each additional medication multiplying the hazard of an ADR episode by 1.14 (95% CI 1.09, 1.20). ADRs directly increased length of stay in 147 (26.8%) patients. The drugs most frequently associated with ADRs were diuretics, opioid analgesics, and anticoagulants. In conclusion, approximately one in seven hospital in-patients experience an ADR, which is a significant cause of morbidity, increasing the length of stay of patients by an average of 0.25 days/patient admission episode. The overall burden of ADRs on hospitals is high, and effective intervention strategies are urgently needed to reduce this burden

An embedded longitudinal multi-faceted qualitative evaluation of a complex cluster randomized controlled trial aiming to reduce clinically important errors in medicines management in general practice

<p>Abstract</p> <p>Background</p> <p>There is a need to shed light on the pathways through which complex interventions mediate their effects in order to enable critical reflection on their transferability. We sought to explore and understand key stakeholder accounts of the acceptability, likely impact and strategies for optimizing and rolling-out a successful pharmacist-led information technology-enabled (PINCER) intervention, which substantially reduced the risk of clinically important errors in medicines management in primary care.</p> <p>Methods</p> <p>Data were collected at two geographical locations in central England through a combination of one-to-one longitudinal semi-structured telephone interviews (one at the beginning of the trial and another when the trial was well underway), relevant documents, and focus group discussions following delivery of the PINCER intervention. Participants included PINCER pharmacists, general practice staff, researchers involved in the running of the trial, and primary care trust staff. PINCER pharmacists were interviewed at three different time-points during the delivery of the PINCER intervention. Analysis was thematic with diffusion of innovation theory providing a theoretical framework.</p> <p>Results</p> <p>We conducted 52 semi-structured telephone interviews and six focus group discussions with 30 additional participants. In addition, documentary data were collected from six pharmacist diaries, along with notes from four meetings of the PINCER pharmacists and feedback meetings from 34 practices. Key findings that helped to explain the success of the PINCER intervention included the perceived importance of focusing on prescribing errors to all stakeholders, and the credibility and appropriateness of a pharmacist-led intervention to address these shortcomings. Central to this was the face-to-face contact and relationship building between pharmacists and a range of practice staff, and pharmacists’ explicitly designated role as a change agent. However, important concerns were identified about the likely sustainability of this new model of delivering care, in the absence of an appropriate support network for pharmacists and career development pathways.</p> <p>Conclusions</p> <p>This embedded qualitative inquiry has helped to understand the complex organizational and social environment in which the trial was undertaken and the PINCER intervention was delivered. The longitudinal element has given insight into the dynamic changes and developments over time. Medication errors and ways to address these are high on stakeholders’ agendas. Our results further indicate that pharmacists were, because of their professional standing and skill-set, able to engage with the complex general practice environment and able to identify and manage many clinically important errors in medicines management. The transferability of the PINCER intervention approach, both in relation to other prescribing errors and to other practices, is likely to be high.</p

Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions – A Meta-Analysis

BACKGROUND: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. METHODS: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. RESULTS: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable. CONCLUSIONS: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research