Darren M. Ashcroft

Global epidemiology of psoriasis: a systematic review of incidence and prevalence.

The worldwide incidence and prevalence of psoriasis is poorly understood. To better understand this, we performed a systematic review of published population-based studies on the incidence and prevalence of psoriasis. Three electronic databases were searched from their inception dates to July 2011. A total of 385 papers were critically appraised; 53 studies reported on the prevalence and incidence of psoriasis in the general population. The prevalence in children ranged from 0% (Taiwan) to 2.1% (Italy), and in adults it varied from 0.91% (United States) to 8.5% (Norway). In children, the incidence estimate reported (United States) was 40.8/100,000 person-years. In adults, it varied from 78.9/100,000 person-years (United States) to 230/100,000 person-years (Italy). The data indicated that the occurrence of psoriasis varied according to age and geographic region, being more frequent in countries more distant from the equator. Prevalence estimates also varied in relation to demographic characteristics in that studies confined to adults reported higher estimates of psoriasis compared with those involving all age groups. Studies on the prevalence and incidence of psoriasis have contributed to a better understanding of the burden of the disease. However, further research is required to fill existing gaps in understanding the epidemiology of psoriasis and trends in incidence over time.

Hospital admissions associated with adverse drug reactions: A systematic review of prospective observational studies

Objective: To determine the prevalence of hospital admissions associated with ADRs and examine differences in prevalence rates between population groups and methods of ADR detection. Data Sources: Studies were identified through electronic searches of Cumulative Index to Nursing and Allied Hearth Literature. EMBASE, and MEDLINE to August 2007. There were no language restrictions. Study Selection and Data Extraction: A systematic review was conducted of prospective observational studies that used the World Health Organization ADR definition. Subgroup analysis examined the influence of patient age groups and methods of ADR detection on reported ADR admission rates. All statistical analyses were performed using STATA v 9.0. Data Synthesis: Twenty-five studies were identified including 106, 586 patients who were hospitalized; 2143 of these patients had experienced ADRs. The prevalence rates of ADRs ranged from 0.16% to 15.7%, with an overall median of 5.3% (interquartile range [IQR] 2.7–9.0%). Median ADR prevalence rates varied between age groups: for children, the ADR admission rate was 4.1% (IQR 0.16–5.3%), while the corresponding rates for adults and elderly patients were 6.3% (IQR 3.9–9.0%) and 10.7% (IQR 9.6–13.3%), respectively. ADR rates also varied depending on the methods of ADR detection employed in the different studies. Studies that employed multiple ADR detection methods, such as medical record review and patient interview, reported higher ADR admission rates compared with studies that used medical record review alone. Antiinfective drugs were most often associated with ADR admissions in children; cardiovascular drugs were most often associated with ADR admissions in adults and elderly patients. Conclusions: Approximately 5.3% of hospital admissions were associated with ADRs. Higher rates were found in elderly patients who are likely to be receiving multiple medications for long-term illnesses. The methods used to detect ADRs are also likely to explain much of the variation in the reported ADR prevalence rates between different studies.

Prevalence, incidence and nature of prescribing errors in hospital inpatients: a systematic review.

Prescribing errors affect patient safety throughout hospital practice. Previous reviews of studies have often targeted specific populations or settings, or did not adopt a systematic approach to reviewing the literature. Therefore, we set out to systematically review the prevalence, incidence and nature of prescribing errors in hospital inpatients. MEDLINE, EMBASE, CINAHL and International Pharmaceutical Abstracts (all from 1985 to October 2007) were searched for studies of prescriptions for adult or child hospital inpatients giving enough data to calculate an error rate. Electronic prescriptions and errors for single diseases, routes of administration or types of prescribing error were excluded, as were non-English language publications. Median error rate (interquartile range [IQR]) was 7% (2–14%) of medication orders, 52 (8–227) errors per 100 admissions and 24 (6–212) errors per 1000 patient days. Most studies (84%) were conducted in single hospitals and originated from the US or UK (72%). Most errors were intercepted and reported before they caused harm, although two studies reported adverse drug events. Errors were most common with antimicrobials and more common in adults (median 18% of orders [ten studies, IQR 7–25%]) than children (median 4% [six studies, IQR 2–17%]). Incorrect dosage was the most common error.Overall, it is clear that prescribing errors are a common occurrence, affecting 7% of medication orders, 2% of patient days and 50% of hospital admissions. However, the reported rates of prescribing errors varied greatly and this could be partly explained by variations in the definition of a prescribing error, the methods used to collect error data and the setting of the study. Furthermore, a lack of standardization between severity scales prevented any comparison of error severity across studies. Future research should address the wide disparity of data-collection methods and definitions that bedevils comparison of error rates or meta-analysis of different studies.

Causes of Medication Administration Errors in Hospitals: a Systematic Review of Quantitative and Qualitative Evidence

BackgroundUnderlying systems factors have been seen to be crucial contributors to the occurrence of medication errors. By understanding the causes of these errors, the most appropriate interventions can be designed and implemented to minimise their occurrence.ObjectiveThis study aimed to systematically review and appraise empirical evidence relating to the causes of medication administration errors (MAEs) in hospital settings.Data SourcesNine electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA, PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium and Social Science Citations Index) were searched between 1985 and May 2013.Study SelectionInclusion and exclusion criteria were applied to identify eligible publications through title analysis followed by abstract and then full text examination. English language publications reporting empirical data on causes of MAEs were included. Reference lists of included articles and relevant review papers were hand searched for additional studies. Studies were excluded if they did not report data on specific MAEs, used accounts from individuals not directly involved in the MAE concerned or were presented as conference abstracts with insufficient detail.Data Appraisal and Synthesis MethodsA total of 54 unique studies were included. Causes of MAEs were categorised according to Reason’s model of accident causation. Studies were assessed to determine relevance to the research question and how likely the results were to reflect the potential underlying causes of MAEs based on the method(s) used.ResultsSlips and lapses were the most commonly reported unsafe acts, followed by knowledge-based mistakes and deliberate violations. Error-provoking conditions influencing administration errors included inadequate written communication (prescriptions, documentation, transcription), problems with medicines supply and storage (pharmacy dispensing errors and ward stock management), high perceived workload, problems with ward-based equipment (access, functionality), patient factors (availability, acuity), staff health status (fatigue, stress) and interruptions/distractions during drug administration. Few studies sought to determine the causes of intravenous MAEs. A number of latent pathway conditions were less well explored, including local working culture and high-level managerial decisions. Causes were often described superficially; this may be related to the use of quantitative surveys and observation methods in many studies, limited use of established error causation frameworks to analyse data and a predominant focus on issues other than the causes of MAEs among studies.LimitationsAs only English language publications were included, some relevant studies may have been missed.ConclusionsLimited evidence from studies included in this systematic review suggests that MAEs are influenced by multiple systems factors, but if and how these arise and interconnect to lead to errors remains to be fully determined. Further research with a theoretical focus is needed to investigate the MAE causation pathway, with an emphasis on ensuring interventions designed to minimise MAEs target recognised underlying causes of errors to maximise their impact.

Prevalence of Adverse Drug Events in Ambulatory Care: A Systematic Review

Objective: Most medications are prescribed, dispensed, and administered in ambulatory care settings, yet little information exists on the adverse effects of drugs in this setting. This review was conducted to estimate the prevalence of adverse drug events (ADEs) and the proportion of preventable ADEs in ambulatory care settings; compare data for different age groups including children, adults, and elderly patients; and review drug classes most commonly associated with ADEs. Data Sources: Four electronic databases–PubMed (1966-March 2011), International Pharmaceutical Abstracts (1970-March 2011), EMBASE (1980-March 2011), and the Cochrane Database of Systematic Reviews (1993-March 2011)—were systematically searched for published data. Bibliographies of retrieved articles were searched individually for additional relevant studies. Study Selection: A standardized definition of an ADE was used to select studies in populations living in the community, with medical visits to primary care facilities, nonspecialty ambulatory care facilities, and/or admissions to a hospital for medication-related adverse events. Data Extraction: Data were extracted using a standardized table. Forty-three studies met our inclusion criteria. Data Synthesis: The median ADE prevalence rate for retrospective studies was 3.3% (interquartile range [IQR] 2.3-7.1%) vs 9.65% (IQR 3.3-17.35%) for prospective studies. Median preventable ADE rates in ambulatory care–based studies were 16.5%, and 52.9% for hospital-based studies. Median prevalence rates by age group ranged from 2.45% for children to 5.27% for adults, 16.1% for elderly patients, and 3.45% for studies including all ages. Conclusions: Despite a recent increase in publications on ADEs in the ambulatory care setting, most studies remain hospital based. Notable differences in prevalence rates by age groups and by responsible drug categories provide guidance on how to direct attention toward effective targets for improvement of medication safety in ambulatory care settings.

Prevalence and Nature of Medication Administration Errors in Health Care Settings: A Systematic Review of Direct Observational Evidence:

OBJECTIVE: To systematically review empirical evidence on the prevalence and nature of medication administration errors (MAEs) in health care settings. DATA SOURCES: Ten electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, Scopus, Applied Social Sciences Index and Abstracts, PsycINFO, Cochrane Reviews and Trials, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, and Health Management Information Consortium) were searched (1985-May 2012). STUDY SELECTION AND DATA EXTRACTION: English-language publications reporting MAE data using the direct observation method were included, providing an error rate could be determined. Reference lists of all included articles were screened for additional studies. DATA SYNTHESIS: In all, 91 unique studies were included. The median error rate (interquartile range) was 19.6% (8.6–28.3%) of total opportunities for error including wrong-time errors and 8.0% (5.1–10.9%) without timing errors, when each dose could be considered only correct or incorrect. The median rate of error when more than 1 error could be counted per dose was 25.6% (20.8–41.7%) and 20.7% (9.7–30.3%), excluding wrong-time errors. A higher median MAE rate was observed for the intravenous route (53.3% excluding timing errors (IQR 26.6–57.9%)) compared to when all administration routes were studied (20.1%; 9.0–24.6%), where each dose could accumulate more than one error. Studies consistently reported wrong time, omission, and wrong dosage among the 3 most common MAE subtypes. Common medication groups associated with MAEs were those affecting nutrition and blood, gastrointestinal system, cardiovascular system, central nervous system, and antiinfectives. Medication administration error rates varied greatly as a product of differing medication error definitions, data collection methods, and settings of included studies. Although MAEs remained a common occurrence in health care settings throughout the time covered by this review, potential targets for intervention to minimize MAEs were identified. CONCLUSIONS: Future research should attend to the wide methodological inconsistencies between studies to gain a greater measure of comparability to help guide any forthcoming interventions.

Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register

Objective To evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA). Method This analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan–Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference. Results One-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence. Conclusions These results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drugs effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

The Causes of and Factors Associated with Prescribing Errors in Hospital Inpatients: A Systematic Review

Prescribing errors are common, they result in adverse events and harm to patients and it is unclear how best to prevent them because recommendations are more often based on surmized rather than empirically collected data. The aim of this systematic review was to identify all informative published evidence concerning the causes of and factors associated with prescribing errors in specialist and non-specialist hospitals, collate it, analyse it qualitatively and synthesize conclusions from it.Seven electronic databases were searched for articles published between 1985–July 2008. The reference lists of all informative studies were searched for additional citations. To be included, a study had to be of handwritten prescriptions for adult or child inpatients that reported empirically collected data on the causes of or factors associated with errors. Publications in languages other than English and studies that evaluated errors for only one disease, one route of administration or one type of prescribing error were excluded.Seventeen papers reporting 16 studies, selected from 1268 papers identified by the search, were included in the review. Studies from the US and the UK in university-affiliated hospitals predominated (10/16 [62%]). The definition of a prescribing error varied widely and the included studies were highly heterogeneous. Causes were grouped according to Reason’s model of accident causation into active failures, error-provoking conditions and latent conditions. The active failure most frequently cited was a mistake due to inadequate knowledge of the drug or the patient. Skills-based slips and memory lapses were also common. Where error-provoking conditions were reported, there was at least one per error. These included lack of training or experience, fatigue, stress, high workload for the prescriber and inadequate communication between healthcare professionals. Latent conditions included reluctance to question senior colleagues and inadequate provision of training.Prescribing errors are often multifactorial, with several active failures and error-provoking conditions often acting together to cause them. In the face of such complexity, solutions addressing a single cause, such as lack of knowledge, are likely to have only limited benefit. Further rigorous study, seeking potential ways of reducing error, needs to be conducted. Multifactorial interventions across many parts of the system are likely to be required.

Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: Observational study from the British Society of Rheumatology Biologics Register

IntroductionAnti-TNF therapies represent a breakthrough in the treatment of severe psoriatic arthritis. However, little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice. The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a prospective cohort of psoriatic arthritis patients and to identify factors associated with and reasons for drug discontinuation.MethodsA total of 566 patients with psoriatic arthritis were registered with the British Society for Rheumatology Biologics Register (first anti-TNF agent: etanercept, n = 316; infliximab, n = 162; and adalimumab, n = 88). Treating physicians completed 6-monthly follow-up questionnaires detailing changes to anti-TNF therapies. Persistence with treatment was examined using Kaplan–Meier survival analysis. Reasons for withdrawal were classified as due to inefficacy, adverse events or other reasons. Univariate and multivariate Cox proportional hazard models were developed to examine potential predictors of withdrawals due to inefficacy or adverse events, using a range of demographic, baseline disease-specific and therapeutic variables.ResultsAt baseline, the mean (standard deviation) age of patients was 45.7 (11.1) years, 53% were female and the mean disease duration was 12.4 (8.7) years. Persistence data were available for a mean (standard deviation) follow-up of 2.3 (0.9) person-years. In total, 422 patients had completed at least 12 months of follow-up, 75.5% of whom remained on their first anti-TNF drug while 9.5% discontinued due to inefficacy, 10.0% due to adverse events and 5.0% due to other reasons. During the period of follow-up, 178 patients received a second anti-TNF therapy. The survivor function on second anti-TNF for switchers was 74% at 12 months.ConclusionsPsoriatic arthritis patients show high persistence rates with both initial and second anti-TNF therapies.