Adverse drug events in older hospitalized patients: results and reliability of a comprehensive and structured identification strategy.

BACKGROUND: Older patients are at high risk for experiencing Adverse Drug Events (ADEs) during hospitalization. To be able to reduce ADEs in these vulnerable patients, hospitals first need to measure the occurrence of ADEs, especially those that are preventable. However, data on preventable ADEs (pADEs) occurring during hospitalization in older patients are scarce, and no 'gold standard' for the identification of ADEs exists. METHODOLOGY: The study was conducted in three hospitals in the Netherlands in 2007. ADEs were retrospectively identified by a team of experts using a comprehensive and structured patient chart review (PCR) combined with a trigger-tool as an aid. This ADE identification strategy was applied to a cohort of 250 older hospitalized patients. To estimate the intra- and inter-rater reliabilities, Cohen's kappa values were calculated. PRINCIPAL FINDINGS: In total, 118 ADEs were detected which occurred in 62 patients. This ADE yield was 1.1 to 2.7 times higher in comparison to other ADE studies in older hospitalized patients. Of the 118 ADEs, 83 (70.3%) were pADEs; 51 pADEs (43.2% of all ADEs identified) caused serious patient harm. Patient harm caused by ADEs resulted in various events. The overall intra-rater agreement of the developed strategy was substantial (κ = 0.74); the overall inter-rater agreement was only fair (κ = 0.24). CONCLUSIONS/SIGNIFICANCE: The ADE identification strategy provided a detailed insight into the scope of ADEs occurring in older hospitalized patients, and showed that the majority of (serious) ADEs can be prevented. Several strategy related aspects, as well as setting/study specific aspects, may have contributed to the results gained. These aspects should be considered whenever ADE measurements need to be conducted. The results regarding pADEs can be used to design tailored interventions to effectively reduce harm caused by medication errors. Improvement of the inter-rater reliability of a PCR remains challenging.

Changes in adverse event rates in hospitals over time: a longitudinal retrospective patient record review study.

OBJECTIVE: To determine the change in adverse event (AE) rates and preventable AE rates over time, identify certain patient risk groups and discuss factors influencing the outcome. DESIGN: Longitudinal retrospective patient record review study. SETTING AND PARTICIPANTS: A random sample of 21 hospitals in The Netherlands in 2004, and 20 hospitals in 2008. In each hospital, 400 patient admissions were included in 2004, and 200 in 2008. MAIN OUTCOME MEASURES: AEs and preventable AEs. RESULTS: Multilevel analyses of 11 883 patient records (7.887 in 2004, 3.996 in 2008) showed that the rate of patients experiencing an AE increased from 4.1% (95% CI 3.3% to 5.1%) in 2004 to 6.2% (95% CI 5.0% to 7.6%) in 2008. The preventable AE rate remained relatively stable at 1.8% (95% CI 1.3% to 2.4%) in 2004 and 1.6% (95% CI 1.2% to 2.3%) in 2008. The risk of experiencing a preventable AE was increasingly higher for patients admitted to a surgical unit (OR 1.54 (95% CI 1.10 to 2.16) in 2004 and 3.32 (95% CI 2.17 to 5.07)) in 2008. More than 50% of all AEs were related to surgery. Indications were found that differences in the risk of experiencing a preventable AE between hospital departments were larger in 2008 than in 2004, while differences between hospitals themselves were smaller. CONCLUSIONS: Patient harm related to healthcare is a persistent problem that is hard to influence. Measuring AEs over time stresses the continuing urgency, and also identifies possible areas for improvement.

A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.

OBJECTIVE: Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. DESIGN: A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses. RESULTS: In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population. CONCLUSIONS: The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.

Nature, occurrence and consequences of medication-related adverse events during hospitalization: a retrospective chart review in the Netherlands.

BACKGROUND: Medication-related adverse events (MRAEs) form a large proportion of all adverse events in hospitalized patients and are associated with considerable preventable harm. Detailed information on harm related to drugs administered during hospitalization is scarce. Knowledge of the nature and preventability of MRAEs is needed to prioritize and improve medication-related patient safety. OBJECTIVE: To provide information on the nature, consequences and preventability of MRAEs occurring during hospitalization in the Netherlands. STUDY DESIGN: Analysis of MRAEs identified in a retrospective chart review of patients hospitalized during 2004. METHODS: The records of 7889 patients admitted to 21 hospitals in 2004 were reviewed by trained nurses and physicians using a three-stage process. For each hospital, patient records of 200 discharged and 200 deceased patients were randomly selected and reviewed. For each patient record, characteristics of the patient and the admission were collected. After identification of an MRAE the physician reviewers determined the type, severity, preventability, drug category and excess length of stay associated with the MRAE. Data on additional interventions or procedures related to MRAEs were obtained by linking our data to the national hospital registration database. The excess length of stay and the additional medical procedures were multiplied by unit costs to estimate the total excess direct medical costs associated with the MRAE. RESULTS: In total, 148 MRAEs occurred in 140 hospital admissions. The incidence of MRAEs was 0.9% (95% CI 0.7, 1.2) and the incidence of preventable MRAEs was 0.2% (95% CI 0.1, 0.4) per hospital admission. The majority of non-preventable MRAEs were adverse drug reactions caused by cancer chemotherapy. Preventable MRAEs were most often found in relation to anticoagulant treatment administered in combination with NSAIDs. Both non-preventable and preventable MRAEs resulted in considerable excess length of hospital stay and costs. On average, MRAEs resulted in an excess length of stay of 6.2 days (95% CI 3.6, 8.8) and average additional costs of &U20AC;2507 (95% CI 1520, 3773). CONCLUSIONS: This study was the first to provide detailed information on MRAEs during hospital admissions in the Netherlands, which were associated with both considerable patient harm and additional medical costs. To increase patient safety, interventions need to be developed that reduce the burden of MRAEs. These interventions should target the areas with the highest risk of MRAEs, notably antibacterials, cancer treatment, anticoagulant treatment and drug therapy in elderly patients.

Direct medical costs of adverse events in Dutch hospitals.

BACKGROUND: Up to now, costs attributable to adverse events (AEs) and preventable AEs in the Netherlands were unknown. We assessed the total direct medical costs associated with AEs and preventable AEs in Dutch hospitals to gain insight in opportunities for cost savings. METHODS: Trained nurses and physicians retrospectively reviewed 7,926 patient records in 21 hospitals. Additional patient information of 7,889 patients was received from the Dutch registration of hospital information. Direct medical costs attributable to AEs were assessed by measuring excess length of stay and additional medical procedures after an AE occurred. Costs were valued using Dutch standardized cost prices. RESULTS: The annual direct medical costs in Dutch hospitals were estimated at a total of euro 355 million for all AEs and euro 161 million for preventable AEs in 2004. The total number of hospital admissions in which a preventable AE occurred was 30,000 (2.3% of all admissions) and more than 300,000 (over 3% of all bed days) bed days were attributable to preventable AEs in 2004. Multilevel analysis showed that variance in direct medical costs was not determined by differences between hospitals or hospital departments. CONCLUSION: The estimates of the total preventable direct medical costs of AEs indicate that they form a substantial part (1%) of the expenses of the national health care budget and are of importance to hospital management. The cost driver of the direct medical costs is the excess length of stay (including readmissions) in a hospital. Insight in which determinants are associated with high preventable costs will offer useful information for policymakers and hospital management to determine starting points for interventions to reduce the costs of preventable AEs.

Is physical examination required before prescribing hormones to patients with gender dysphoria?

INTRODUCTION: A genital examination can have psychologic effects on a patient, particularly when the source of their sexual medicine complaint is a body part. How necessary is a physical exam before prescribing hormones in cases of gender dsyphoria? METHODS: Five people with expertise and/or interest in the area of gender dysphoria and endocrinology were asked to contribute their opinions. MAIN OUTCOME MEASURE: To provide food for thought, discussion, and possible further research in a poorly discussed area of sexual medicine. RESULTS: Of the five experts writing on the topic, one believes that a physical examination should always be performed before prescribing hormones for gender dysphoria, one believes it is not a prerequisite, and three believe a physical examination is recommended, but is not necessary in cases where the patient objects despite an explanation of the purpose of the exam. As long as this was documented, it would not present a medicolegal problem. CONCLUSIONS: It is not clear whether or not a physical examination must be performed on all gender dsyphoric patients before prescribing hormones; however, an examination would be helpful in revealing a significant health management issue.

Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects.

OBJECTIVE: Sex differences are found in most components of the insulin resistance syndrome and the associated cardiovascular risk profile. These differences are attributed to sex-specific sex steroid profiles, but the effects of sex steroids on the individual components of the insulin resistance syndrome remain incompletely understood. DESIGN: Prospective, intervention study. SUBJECTS: In 37 young (age range 16-36 years), nonobese [body mass index (BMI) < 29], transsexual subjects, effects of ethinyl oestradiol (100 micro g/day) + cyproterone acetate (100 mg/day) administration were evaluated in 20 male-to-female transsexuals and of testosterone-ester administration [250 mg intramuscularly (i.m.)/2 weeks] in 17 female-to-male transsexuals. MEASUREMENTS: We studied lipid spectrum, postheparin hepatic lipase (HL) and lipoprotein lipase (LPL) activity, blood pressure, glucose utilization (by euglycaemic hyperinsulinaemic clamp), and fat areas (by magnetic resonance imaging) at baseline and during 1-year cross-sex hormone administration. RESULTS: Oestrogens + antiandrogens increased high-density lipoprotein (HDL)-cholesterol and decreased LDL-cholesterol, and HL activity, which are considered beneficial. But this combination also increased triglycerides, blood pressure, subcutaneous fat and visceral fat, and decreased the LDL-particle size, LPL activity and insulin sensitivity, which are all considered detrimental. Testosterone reduced HDL-cholesterol and the LDL-particle size, and increased triglycerides and HL activity. An android fat distribution was induced (i.e. decreased subcutaneous and increased visceral fat). Blood pressure, total and LDL-cholesterol, LPL activity and insulin sensitivity were mainly unaffected. CONCLUSIONS: The effects of cross-sex hormone treatment - in the dosages used in this study - in healthy, nonobese, young transsexual subjects do not show unequivocally that female sex steroids, given in large amounts to male subjects, have beneficial effects on cardiovascular profile and that high dose testosterone administration to female subjects is detrimental with respect to cardiovascular risk.