A patient's perspective:the impact of adverse drug reactions on patients and their views on reporting

What is known and objective: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self-reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. Method: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi-structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient's reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients'responses was performed. Results and discussion: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient's 'job'. What is new and conclusion: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic. © 2011 Blackwell Publishing Ltd.

Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease

Background - Previous Cochrane reviews have considered the use of cholinesterase inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The clinical features of DLB and PDD have much in common and are distinguished primarily on the basis of whether or not parkinsonism precedes dementia by more than a year. Patients with both conditions have particularly severe deficits in cortical levels of the neurotransmitter acetylcholine. Therefore, blocking its breakdown using cholinesterase inhibitors may lead to clinical improvement. Objectives - To assess the efficacy, safety and tolerability of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and cognitive impairment in Parkinson’s disease falling short of dementia (CIND-PD) (considered as separate phenomena and also grouped together as Lewy body disease). Search methods - The trials were identified from a search of ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (on 30 August 2011) using the search terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing trial databases and is updated regularly. Reference lists of relevant studies were searched for additional trials. Selection criteria - Randomised, double-blind, placebo-controlled trials assessing the efficacy of treatment with cholinesterase inhibitors in DLB, PDD and cognitive impairment in Parkinson’s disease (CIND-PD). Data collection and analysis - Data were extracted from published reports by one review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD) were considered separately and, where possible, also pooled together. Statistical analysis was conducted using Review Manager version 5.0. Main results - Six trials met the inclusion criteria for this review, in which a total of 1236 participants were randomised. Four of the trials were of a parallel group design and two cross-over trials were included. Four of the trials included participants with a diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre 2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included patients with cognitive impairment and Parkinson's disease (both with and without dementia). Patients with dementia with Lewy bodies (DLB) were included in only one of the trials (McKeith 2000). For global assessment, three trials comparing cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004; Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001). For cognitive function, a pooled estimate of the effect of cholinesterase inhibitors on cognitive function measures was consistent with the presence of a therapeutic benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P < 0.00001). There was evidence of a positive effect of cholinesterase inhibitors on the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI 0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95% CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial. For behavioural disturbance, analysis of the pooled continuous data relating to behavioural disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.36 to -0.04, P = 0.01). For activities of daily living, combined data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03). For safety and tolerability, those taking a cholinesterase inhibitor were more likely to experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI 1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI 1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001) but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to 1.80, P = 0.25). Parkinsonian symptoms in particular tremor (64/739 versus 12/352; OR 2.71, 95% CI 1.44 to 5.09, P = 0.002), but not falls (P = 0.39), were reported more commonly in the treatment group but this did not have a significant impact on the UPDRS (total and motor) scores (P = 0.71). Fewer deaths occurred in the treatment group than in the placebo group (4/465 versus 9/279; OR 0.28, 95% CI 0.09 to 0.84, P = 0.03). Authors' conclusions - The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.

Ranibizumab versus Bevacizumab to treat neovascular age-related macular degeneration:one-year findings from the IVAN Randomized Trial

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P

The impact of statin use on fetal development:a meta-analysis

INTRODUCTION: Statin use inadvertently during pregnancy and proposed use of statins for the treatment of preeclampsia, led us to question the evidence behind their current contraindicated status. Several studies have evaluated the relationship between statin use in pregnancy with fetal outcome but their results have not been quantitatively assessed by meta-analysis. Our objective was to undertake a systematic review of all published clinical evidence to assess the effects of statin use in pregnancy on subsequent fetal wellbeing. METHODS: A comprehensive search strategy was performed of all electronic databases and the Merck reporting database for studies published from 1966 to 2014. Two reviewers independently screened citations and undertook study quality assessment and data extraction. We obtained summary estimates of adverse fetal events that were classified as potentially fatal, clinically significant morbidity or minor adverse event. We identified 602 titles and reviewed 30 articles for inclusion and exclusion criteria. Meta-analysis was performed on seven studies (3 cohort, 3 case-series and 1 case-control). RESULTS: Of the 922 cases of statin exposure in pregnancy, 27 exposures were associated with lethal or clinically significant fetal morbidity and 10 with minor adverse events. Statin exposure was limited to the first trimester in all but two cases. The pooled rate of lethal or clinically significant fetal abnormalities in pregnant women exposed to statins was 0.01 (95% CI 0.00-0.04), less than the European rate of 0.026 (95% CI 2.54- 2.57)EUROCAT. The rate of fetal abnormality for simvastatin was 0.03 (95% CI 0.00-0.08), atorvostatin 0.11 (95% CI 0.00-0.52), pravastatin 0.01 (95% CI 0.00-0.2) and lovastatin use 0.04 (95% CI 0.00-0.28). Systems based anomalies were also calculated, congenital heart disease was 0.8 (95% CI 0.02-0.12) compared with the background rate of 0.79 (95% CI 0.78- 0.80). CONCLUSIONS: The published data suggests that statins may not be teratogenic when given inadvertently during pregnancy and prospective studies such as The StAmP Trial may provide more data

Neurodegeneration is an early event in diabetic retinopathy:therapeutic implications

Diabetic retinopathy (DR) remains the leading cause of blindness among working-age individuals in developed countries. Current treatments for DR are indicated in advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. DR has been classically considered to be a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the underlying mechanisms that lead to neurodegeneration will be essential for identifying new therapeutic targets. From the clinical point of view, the identification of those patients in whom retinal neurodegeneration appears will be crucial for implementing early treatment based on neuroprotective drugs. When the early stages of DR are the therapeutic target, it would be inconceivable to recommend an aggressive treatment such as intravitreous injections. By contrast, topical administration of neuroprotective drugs by using eye drops is a possible option. However, clinical trials to determine the safety and effectiveness of this non-invasive route, as well as a standardisation of the methods for monitoring neurodegeneration, are needed.

Patient experiences of serious adverse drug reactions and their attitudes to medicines:a qualitative study of survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK

Background: Adverse drug reactions (ADRs) cause significant morbidity and mortality and account for around 6.5% of hospital admissions. Patient experiences of serious ADRs and their long-term impact on patients' lives, including their influence on current attitudes towards medicines, have not been previously explored. Objective: The aim of the study was to explore the experiences, beliefs, and attitudes of survivors of serious ADRs, using drug-induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) as a paradigm. Methods: A retrospective, qualitative study was undertaken using detailed semi-structured interviews. Fourteen adult survivors of SJS and TEN, admitted to two teaching hospitals in the UK, one the location of a tertiary burns centre, were interviewed. Interview transcripts were independently analysed by three different researchers and themes emerging from the text identified. Results: All 14 patients were aware that their condition was drug induced, and all but one knew the specific drug(s) implicated. Several expressed surprise at the perceived lack of awareness of the ADR amongst healthcare professionals, and described how the ADR was mistaken for another condition. Survivors believed that causes of the ADR included (i) being given too high a dose of the drug; (ii) medical staff ignoring existing allergies; and (iii) failure to monitor blood tests. Only two believed that the reaction was unavoidable. Those who believed that the condition could have been avoided had less trust in healthcare professionals. The ADR had a persisting impact on their current lives physically and psychologically. Many now avoided medicines altogether and were fearful of becoming ill enough to need them. © 2011 Adis Data Information BV. All rights reserved. Conclusions: Life-threatening ADRs continued to affect patients’ lives long after the event. Patients’ beliefs regarding the cause of the ADR differed, and may have influenced their trust in healthcare professionals and medicines. We propose that clear communication during the acute phase of a serious ADR may therefore be important.