Adverse drug reactions related hospital admissions in persons aged 60 years and over, The Netherlands, 1981-2007: less rapid increase, different drugs

Background

Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population.

Methodology and Principal Findings

Secular trend analysis of ADR-related hospital admissions in patients ≥60 years between 1981 and 2007, using the National Hospital Discharge Registry of the Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ≥60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981–1996 (percentage annual change 2.56%).

Conclusion/Significance

ADR-related hospital admissions in older persons have shown a rapidly increasing trend in the Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem.     

Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria

Background  

Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR reporting and to suggest possible ways of improving this method of reporting.     

Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database

Background

Spontaneous reporting of adverse drug reactions (ADRs) is an important method for pharmacovigilance, but under-reporting and poor quality of reports are major limitations. The aim of this study was to evaluate if repeated one-page ADR information letters affect (i) the reporting rate of ADRs and (ii) the quality of the ADR reports.

Methods

All 151 primary healthcare units in the Region Västra Götaland, Sweden, were randomly allocated (1:1) to an intervention (n = 77) or a control group (n = 74). The intervention consisted of one-page ADR information letters administered at three occasions during 2008 to all physicians and nurses in the intervention units. The number of ADR reports received from the 151 units was registered, as was the quality of the reports, which was defined as high if the ADR was to be reported according to Swedish regulations, that is, if the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new drugs and not labelled as common in the Summary of Product Characteristics. A questionnaire was administered to evaluate if the ADR information letter had reached the intended recipient.

Results

Before the intervention, no significant differences in reporting rate or number of high quality reports could be detected between the randomization groups. In 2008, 79 reports were sent from 37 intervention units and 52 reports from 30 control units (mean number of reports per unit ± standard deviation: 1.0 ± 2.5 vs. 0.7 ± 1.2, P = 0.34). The number of high quality reports was higher in intervention units than in control units (37 vs. 15 reports, 0.5 ± 0.9 vs. 0.2 ± 0.6, P = 0.048). According to the returned questionnaires (n = 1,292, response rate 57%), more persons in the intervention than in the control group had received (29% vs. 19%, P < 0.0001) and read (31% vs. 26%, P < 0.0001) an ADR information letter.

Conclusions

This study suggests that repeated ADR information letters to physicians and nurses do not increase the ADR reporting rate, but may increase the number of high quality reports.     

Disease activity and low physical activity associate with number of hospital admissions and length of hospitalisation in patients with rheumatoid arthritis

Introduction  

Substantial effort has been devoted for devising effective and safe interventions to reduce preventable hospital admissions in chronic disease patients. In rheumatoid arthritis (RA), identifying risk factors for admission has important health policy implications, but knowledge of which factors cause or prevent hospital admissions is currently lacking. We hypothesised that disease activity/severity and physical activity are major predictors for the need of hospitalisation in patients with RA.     

Information about ADRs explored by pharmacovigilance approaches: a qualitative review of studies on antibiotics, SSRIs and NSAIDs

Background  

Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected.     

Bias in Spontaneous Reporting of Adverse Drug Reactions in Japan

Background

Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan’s unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.

Methods

A manufacturer’s database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.

Results

For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.

Conclusions

Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.     

Potential Therapeutic Effect of Natural Killer Cells on Doxorubicin-Resistant Breast Cancer Cells In Vitro

Objective

The aim of this study was to explore the therapeutic effect of natural killer (NK) cells on human doxorubicin-sensitive and resistant breast adenocarcinoma.

Methods

Human doxorubicin-sensitive and resistant breast cancer cell lines (MCF-7 and MCF-7/ADR) were tagged with renilla luciferase (Rluc) (MCF-7/RC and MCF-7/ADR/RC). NK cells were tagged with enhanced firefly luciferase (effluc) using a recombinant retrovirus transfection (NKF). Expression of Rluc, effluc, and NK cell surface markers CD16, CD56 as well as death receptors, DR4 and DR5, were assessed by using flow cytometry. In vitro cytotoxic effect of NK to MCF-7 and MCF-7/ADR was measured and in vivo bioluminescence imaging was also performed to visualize MCF-7/RC, MCF-7/ADR, and NKF in an animal model.

Results

NK92-MI, MCF-7, and MCF-7/ADR cells were successfully labeled with Rluc or effluc. Both the target breast cancer cells (with Rluc) and therapeutic NK cells (with effluc) were noninvasively visualized in nude mice. Doxorubicin-resistant breast cancer cells (MCF-7/ADR) presented a higher expression of DR5 and were more sensitive to NK cells compared with doxorubicin-sensitive breast cancer cells (MCF-7).

Conclusion

The results of present study suggest that NK cell therapy has a therapeutic effect on doxorubicin-sensitive and resistant breast cancer cells.     

Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

Background

Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model.

Methods

We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset).

Results

Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively.

Conclusions

We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.     

Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005

Background  

Adverse drug reactions (ADRs) are a frequent cause of mortality and morbidity to patients worldwide, with great associated costs to the healthcare providers including the NHS in England. We examined trends in hospital admissions associated with adverse drug reaction in English hospitals and the accuracy of national reporting.     

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study

Background  

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India     

Effects of Meteorological Factors on Daily Hospital Admissions for Asthma in Adults: A Time-Series Analysis

Background

There is limited evidence for the impacts of meteorological changes on asthma hospital admissions in adults in Shanghai, China.

Objectives

To quantitatively evaluate the short-term effects of daily mean temperature on asthma hospital admissions.

Methods

Daily hospital admissions for asthma and daily mean temperatures between January 2005 and December 2012 were analyzed. After controlling for secular and seasonal trends, weather, air pollution and other confounding factors, a Poisson generalized additive model (GAM) combined with a distributed lag non-linear model were used to explore the associations between temperature and hospital admissions for asthma.

Results

During the study periods, there were 15,678 hospital admissions for asthma by residents of Shanghai, an average 5.6 per day. Pearson correlation analysis found a significant negative correlation (r = −0.174, P<0.001) between asthma hospitalizations and daily mean temperature (DMT). The DMT effect on asthma increased below the median DMT, with lower temperatures associated with a higher risk of hospital admission for asthma. Generally, the cold effect appeared to be relatively acute, with duration lasting several weeks, while the hot effect was short-term. The relative risk of asthma hospital admissions associated with cold temperature (the 25^th percentile of temperature relative to the median temperature) was 1.20 (95% confidence interval [CI], 1.01∼1.41) at lag0-14. However, warmer temperatures were not associated with asthma hospital admissions.

Conclusions

Cold temperatures may trigger asthmatic attacks. Effective strategies are needed to protect populations at risk from the effects of cold.     

Weekly and Holiday-Related Patterns of Panic Attacks in Panic Disorder: A Population-Based Study

Background

While chronobiological studies have reported seasonal variation in panic attacks (PA) episodes, information on the timing of PA by week-days may enable better understanding of the triggers of PA episodes and thereby provide pointers for suitable interventional approaches to minimize PA attacks. This study investigated weekly variation in potential PA admissions including associations with holidays using a population-based longitudinal, administrative claims-based dataset in an Asian population.

Methods

This study used ambulatory care data from the “Longitudinal Health Insurance Database 2000. We identified 993 patients with panic disorder (PD), and they had 4228 emergency room (ER) admissions for potential PA in a 3-year period between 1 January 2009 and 31 December 2011. One-way analysis of variance (ANOVA) was used to examine associations between the potential PA admissions and holidays/weekend days/work-days of the week.

Results

The daily mean number of potential PA admissions was 3.96 (standard deviation 2.05). One-way ANOVA showed significant differences in potential PA admissions by holiday and day of the week (p<0.001). Daily frequencies showed a trough on Wednesday-Thursday, followed by a sharp increase on Saturday and a peak on Sunday. Potential PA admissions were higher than the daily mean for the sample patients by 29.4% and 22.1%, respectively on Sundays and holidays. Furthermore, the weekly variations were similar for females and males, although females always had higher potential PA admissions on both weekdays and holidays than the males.

Conclusions

We found that potential PA admissions among persons with PD varied systematically by day of the week, with a significant peak on weekends and holidays.     

Risk of Maltreatment-Related Injury: A Cross-Sectional Study of Children under Five Years Old Admitted to Hospital with a Head or Neck Injury or Fracture

Objectives

To determine the predictive value and sensitivity of demographic features and injuries (indicators) for maltreatment-related codes in hospital discharge records of children admitted with a head or neck injury or fracture.

Methods

Study design: Population-based, cross sectional study. Setting: NHS hospitals in England. Subjects: Children under five years old admitted acutely to hospital with head or neck injury or fracture. Data source: Hospital Episodes Statistics, 1997 to 2009. Main outcome measure: Maltreatment-related injury admissions, defined by ICD10 codes, were used to calculate for each indicator (demographic feature and/or type of injury): i) the predictive value (proportion of injury admissions that were maltreatment-related); ii) sensitivity (proportion of all maltreatment-related injury admissions with the indicator).

Results

Of 260,294 childhood admissions for fracture or head or neck injury, 3.2% (8,337) were maltreatment-related. With increasing age of the child, the predictive value for maltreatment-related injury declined but sensitivity increased. Half of the maltreatment-related admissions occurred in children older than one year, and 63% occurred in children with head injuries without fractures or intracranial injury.

Conclusions

Highly predictive injuries accounted for very few maltreatment-related admissions. Protocols that focus on high-risk injuries may miss the majority of maltreated children.     

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool

Aim

To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT).

Methods

A comparison between seven assessors of a new CAT, formulated by an expert focus group, compared with the Naranjo CAT in 80 cases from a prospective observational study and 37 published ADR case reports (819 causality assessments in total).

Main Outcome Measures

Utilisation of causality categories, measure of disagreements, inter-rater reliability (IRR).

Results

The Liverpool ADR CAT, using 40 cases from an observational study, showed causality categories of 1 unlikely, 62 possible, 92 probable and 125 definite (1, 62, 92, 125) and ‘moderate’ IRR (kappa 0.48), compared to Naranjo (0, 100, 172, 8) with ‘moderate’ IRR (kappa 0.45). In a further 40 cases, the Liverpool tool (0, 66, 81, 133) showed ‘good’ IRR (kappa 0.6) while Naranjo (1, 90, 185, 4) remained ‘moderate’.

Conclusion

The Liverpool tool assigns the full range of causality categories and shows good IRR. Further assessment by different investigators in different settings is needed to fully assess the utility of this tool.     

Endoscopic management of hypertensive intraventricular haemorrhage with obstructive hydrocephalus

Background  

Intracranial haemorrhage accounts for 30–60 % of all stroke admissions into a hospital, with hypertension being the main risk factor. Presence of intraventricular haematoma is considered a poor prognostic factor due to the resultant obstruction to CSF and the mass effect following the presence of blood resulting in raised intracranial pressure and hydrocephalus. We report the results following endoscopic decompression of obstructive hydrocephalus and evacuation of haematoma in patients with hypertensive intraventricular haemorrhage.     

Weight bias in graduate school admissions

Objective:

Whether weight bias occurs in the graduate school admissions process is explored here. Specifically, we examined whether body mass index (BMI) was related to letter of recommendation quality and the number of admissions offers applicants received after attending in‐person interviews.

Design and Methods:

Participants were 97 applicants to a psychology graduate program at a large university in the United States. They reported height, weight, and information about their applications to psychology graduate programs. Participants' letters of recommendation were coded for positive and negative statements as well as overall quality.

Results:

Higher BMI significantly predicted fewer post‐interview offers of admission into psychology graduate programs. Results also suggest this relationship is stronger for female applicants. BMI was not related to overall quality or the number of stereotypically weight‐related adjectives in letters of recommendation. Surprisingly, higher BMI was related to more positive adjectives in letters.

Conclusions:

The first evidence that individuals interviewing applicants to graduate programs may systematically favor thinner applicants is provided here. A conscious or unconscious bias against applicants with extra body weight is a plausible explanation. Stereotype threat and social identity threat are also discussed as explanations for the relationship between BMI and interview success.     

The High Cost of HIV-Positive Inpatient Care at an Urban Hospital in Johannesburg,South Africa

Background

While most HIV care is provided on an outpatient basis, hospitals continue to treat serious HIV-related admissions, which is relatively resource-intensive and expensive. This study reports the primary reasons for HIV-related admission at a regional, urban hospital in Johannesburg, South Africa and estimates the associated lengths of stay and costs.

Methods and Findings

A retrospective cohort study of adult, medical admissions was conducted. Each admission was assigned a reason for admission and an outcome. The length of stay was calculated for all patients (N = 1,041) and for HIV-positive patients (n = 469), actual utilization and associated costs were also estimated. Just under half were known to be HIV-positive admissions. Deaths and transfers were proportionately higher amongst HIV-positive admissions compared to HIV-negative and unknown. The three most common reasons for admission were tuberculosis and other mycobacterial infections (18%, n = 187), cardiovascular disorders (12%, n = 127) and bacterial infections (12%, n = 121). The study sample utilized a total of 7,733 bed days of those, 55% (4,259/7,733) were for HIV-positive patients. The average cost per admission amongst confirmed HIV-positive patients, which was an average of 9.3 days in length, was $1,783 (United States Dollars).

Conclusions

Even in the era of large-scale antiretroviral treatment, inpatient facilities in South Africa shoulder a significant HIV burden. The majority of this burden is related to patients not on ART (298/469, 64%), and accounts for more than half of all inpatient resources. Reducing the costs of inpatient care is thus another important benefit of expanding access to ART, promoting earlier ART initiation, and achieving rates of ART retention and adherence.     

Rising Obesity-Related Hospital Admissions among Children and Young People in England: National Time Trends Study

Objective

To describe the trends in hospital admissions associated with obesity as a primary diagnosis and comorbidity, and bariatric surgery procedures among children and young people in England.

Design

National time trends study of hospital admissions data between 2000 and 2009.

Participants

Children and young people aged 5 to 19 years who were admitted to hospital with any diagnosis of obesity.

Main outcome measures

Age- and sex-specific admission rates per million children.

Results

Between 2000 and 2009, age- and sex-specific hospital admission rates in 5–19 year olds for total obesity-related diagnoses increased more than four-fold from 93.0 (95% CI 86.0 to 100.0) per million children to 414.0 (95% CI 410.7 to 417.5) per million children, largely due to rising admissions where obesity was mentioned as a co-morbidity. The median age of admission to hospital over the study period was 14.0 years; 5,566 (26.7%) admissions were for obesity and 15,319 (73.3%) mentioned obesity as a comorbidity. Admissions were more common in girls than boys (56.2% v 43.8%). The most common reasons for admission where obesity was a comorbid condition were sleep apnoea, asthma, and complications of pregnancy. The number of bariatric surgery procedures has risen from 1 per year in 2000 to 31 in 2009, with the majority were performed in obese girls (75.6%) aged 13–19 years.

Conclusions

Hospital admission rates for obesity and related comorbid conditions have increased more than four-fold over the past decade amongst children and young people. Although some of the increase is likely to be due to improved case ascertainment, conditions associated with obesity in children and young people are imposing greater challenges for health care providers in English hospitals. Most inpatient care is directed at dealing with associated conditions rather than primary assessment and management of obesity itself.