Aim: to establish the percentage hospital admission related to adverse drug reactions (ADRs) from the data available in the literature. Method: literature search in the Medline database, metaanalysis. Results: from the literature it is revealed that a considerable part of all hospital admissions are related to adverse drug reactions. However, these data are not homogenous, i.e. larger studies display a lower percentage of ADR related hospital admission, while smaller studies display a higher percentage. Subgroup analysis showed that for elderly people the odds of being hospitalised by ADR related problems is 4 times higher than for younger ones (16.6% vs. 4.1%). A considerable part of these hospitalisations can be prevented. Subgroup analysis revealed that in the elderly up to 88% of the ADR related hospitalisations are preventable; for the non-elderly this is only 24%. Comparatively more elderly people are hospitalised than younger ones. Combining these findings, twice as much elderly people are hospitalised by ADR related problems than non-elderly, while preventability of ADR related hospitalisation might yield 7 times more people in the elderly than in the non-elderly. The estimation of the costs of ADR related hospitalisations in the Health Care system in The Netherlands is discussed. Conclusion: many elderly people are hospitalised by ADR related problems; an important part of these hospitalisations can be avoided.

Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies.

Objective To contextualise the degree of harm that comes from unsafe medical care compared with individual health conditions using the global burden of disease (GBD), a metric to determine how much suffering is caused by individual diseases. Design Analytic modelling of observational studies investigating unsafe medical care in countries’ inpatient care settings, stratified by national income, to identify incidence of seven adverse events for GBD modelling. Observational studies were generated through a comprehensive search of over 16 000 articles written in English after 1976, of which over 4000 were appropriate for full text review. Results The incidence, clinical outcomes, demographics and costs for each of the seven adverse events were collected from each publication when available. We used disability-adjusted life years (DALYs) lost as a standardised metric to measure morbidity and mortality due to specific adverse events. We estimate that there are 421 million hospitalisations in the world annually, and approximately 42.7 million adverse events. These adverse events result in 23 million DALYs lost per year. Approximately two-thirds of all adverse events, and the DALYs lost from them, occurred in lowincome and middle-income countries. Conclusions This study provides early evidence that adverse events due to medical care represent a major source of morbidity and mortality globally. Though suffering related to the lack of access to care in many countries remains, these findings suggest the importance of critically evaluating the quality and safety of the care provided once a person accesses health services. While further refinements of the estimates are needed, these data should be a call to global health policymakers to make patient safety an international priority.

https://qualitysafety.bmj.com/content/qhc/22/10/809.full.pdf

The global burden of unsafe medical care: analytic modelling of observational studies

Background 
Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.


Methods and Findings 
We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.


Conclusions 
There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

Adverse Drug Reactions in Children—A Systematic Review

INTRODUCTION Until recently, it was considered unethical or impossible to perform clinical trials of new medicines in children. As a consequence, many medicines used for treating children are insufficiently documented with regard to dosing, efficacy, and safety. The off-label use of drugs has been extensive in treating the pediatric population. This article gives an overview of the extent and types of off-label use of medicines in pediatric populations.

Off-Label Drug Use in Pediatric Patients

Although most commonly used drugs cause adverse effects, some of them with potentially serious consequences, relatively little is known about their economic impact. The purpose of this review is to summarise information describing the cost of treatment of drug-induced adverse effects as an additional cost of pharmaceutical treatment. The focus of this study was limited to the overall economic impact of drug-related morbidity and to the economic analysis of a single class of drugs with different safety profiles. Several studies carried out in the US have investigated adverse drug effects experienced by hospitalised patients and their impact on hospital costs. Patients who developed adverse effects were hospitalised an average of 1.2-3.8 days longer than patients who did not, with additional hospital costs of $US2284-5640 per patient (2000 values). Other research studies in different countries have quantified the incidence and economic consequences of adverse drug effects that occur in the ambulatory setting and that generate hospital admission and emergency department visits. They have shown that preventable adverse effects constitute between 43.3% and 80% of all adverse outcomes leading to emergency visits and hospital admissions, and disproportionately increase healthcare costs. Finally, a recent estimation revealed that in the US the cost of problems linked to drug use in the ambulatory setting exceeded $US177 billion in the year 2000.NSAIDs constitute a widely used class of drugs and they are one of the leading drug classes in causing adverse effects. The acquisition costs of the drugs, as well as the costs for prevention and treatment of adverse effects, determine their cost-effectiveness ratio. Depending on the incidence and severity of adverse effects, the cost per adverse effect avoided ranges from $US215 to $US35 459 (2000 values). According to the contingent valuation methodology, willingness to pay to avoid or reduce the incidence of adverse effects is an indicator of the value individuals associate with the impact of such effects on their well-being. Individuals are willing to pay annually an average of $US240 and $US350, respectively, to avoid vomiting and gastrointestinal distress induced by NSAIDs. Although the results of the different studies reviewed are not strictly comparable because of differences in the severity of adverse effects, the perspective of the analysis, the cost data included and the cost component considered, the data show that, apart from the implications for health, a substantial quantity of resources are used to treat adverse effects.

Assessing the Economic Impact of Adverse Drug Effects

Objective

In Lebanon there is very limited restriction on drug use. Accordingly, self-medication is highly prevalent. This study examined the influence of these factors on the development of drug-related illnesses that lead to hospitalization.



Methods

Patients admitted to the medical and pediatric wards of a tertiary teaching center in Beirut, Lebanon, over a period of 6 months were interviewed and their charts were reviewed. Admissions attributable to adverse drug reactions or therapeutic failures were identified and characterized with respect to demographic factors, medical history, drug intake, and self-medicating behavior. The influence of these variables on the development of drug-related illnesses was examined by logistic regression.



Results

Of 1745 adults and 457 children, there were 177 (10.2%) and 36 (7.9%) drug-related illnesses, respectively. Adverse drug reactions accounted for 7.0% and 5.7% and therapeutic failures for 3.2% and 2.2% of adult and pediatric admissions, respectively. Self-medication was commonly practiced (52.6% of adults and 41.6% of children). Logistic regression analysis revealed that female sex increased the risk of adverse drug reaction in adults, whereas self-medication decreased the risk. In children, the risk of adverse drug reaction was increased in lower socioeconomic groups, whereas the risk of therapeutic failure was increased by a positive history of atopy or drug reaction.



Conclusions

These results provide the first detailed analysis of the problem of drug-related illnesses in a developing country and identify a number of related or risk factors. Despite the lack of regulation of drug dispensing and the unchecked access to drugs in Lebanon, the incidence of drug-related illnesses is not different from that in Western nations. This finding may have relevance to policies of drug regulation in other countries.



Clinical Pharmacology & Therapeutics (1998) 64, 450–461; doi:

Drug-related hospitalization at a tertiary teaching center in Lebanon: Incidence, associations, and relation to self-medicating behavior

The photomicrographs shown below are from a 10-dayold boy who presented to our hospital because of jaundice. On physical examination he was jaundiced and pale but had no hepatosplenomegaly. Studies revealed an indirect bilirubin level of 24 mg/dL, a hemoglobin concentration of 9.5 g/dL, and a reticulocyte count of 6.7%. Forty percent of the erythrocytes in the peripheral smear were pyknocytes (Fig. 1). The serum glutamate oxaloacetate transferase (SGOT) level was 93 IU/L, the direct and indirect Coombs tests were negative, osmotic fragility was normal, triglycerides and cholesterol glucose-6-phosphate dehydrogenase and pyruvate kinase levels were normal, as were the results of liver function tests. Blood, urine, and cerebrospinal fluid cultures were sterile. After a blood transfusion and phototherapy, the bilirubin level dropped progressively. The baby was discharged 7 days later. At 3 months of age his bilirubin was 0.2 mg/dL, pyknocytes were 1.5% (Fig. 2), and there was no evidence of hemolytic anemia. At 7 months of age, the hemoglobin concentration was 12 g/dL, the reticulocyte count was 0.4%, and the pyknocytes were virtually absent. DISCUSSION In 1959 Tuffy et al. (1) described 11 infants with hemolytic anemia in early infancy associated with an increased number of pyknocytes. These cells were described as “much distorted, completely irregular, densely stained erythrocytes, usually appreciably smaller than the undistorted cells, and having from several to many spiny projections.” They coined the term infantile pyknocytosis. The disease is manifested by progressive hemolysis and the appearance of pyknocytes that peaks at 3 to 6 weeks of age. The condition is benign and resolves spontaneously by age 4 to 6 months. The cause of the hemolysis is not understood: the cells may represent a manifestation of the erythrocyte membrane damage secondary to ambient transient changes (e.g., lipids, pH, electrolytes, heat) (2,3), elliptocytosis (4), or glucose-6phosphate dehydrogenase deficiency (5). Occurrence in siblings has been reported as well (1,3,6).

Lama Bahlawan

Papers

Drug-related hospitalization at a tertiary teaching center in Lebanon: Incidence, associations, and relation to self-medicating behavior

Infantile pyknocytosis: a forgotten or a dead diagnosis?

Childhood acute lymphoblastic leukemia managed in tertiary care center in a developing country