The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study.

BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.

Prediction admission in the older population in the Emergency Department: the CLEARED tool.

BACKGROUND: Length of stay (LOS) in the Emergency Department (ED) is correlated with an extended in-hospital LOS and may even increase 30-day mortality. Older patients represent a growing population in the ED and they are especially at risk of adverse outcomes. Screening tools that adequately predict admission could help reduce waiting times in the ED and reduce time to treatment. We aimed to develop and validate a clinical prediction tool for admission, applicable to the aged patient population in the ED. METHODS: Data from 7,606 ED visits of patients aged 70 years and older between 2012 and 2014 were used to develop the CLEARED tool. Model performance was assessed with discrimination using logistic regression and calibration. The model was internally validated by bootstrap resampling in Erasmus Medical Center and externally validated at two other hospitals, Medisch Spectrum Twente (MST) and Leiden University Medical Centre (LUMC). RESULTS: CLEARED contains 10 predictors: body temperature, heart rate, diastolic blood pressure, systolic blood pressure, oxygen saturation, respiratory rate, referral status, the Manchester Triage System category, and the need for laboratory or radiology testing. The internally validated area under the curve (AUC) was 0.766 (95% CI [0.759;0.781]). External validation in MST showed an AUC of 0.797 and in LUMC, an AUC of 0.725. CONCLUSIONS: The developed CLEARED tool reliably predicts admission in elderly patients visiting the ED. It is a promising prompt, although further research is needed to implement the tool and to investigate the benefits in terms of reduction of crowding and LOS in the ED.

The APOP screener and clinical outcomes in older hospitalised internal medicine patients.

BACKGROUND: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group. METHODS: Patients aged ≥ 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk ≥ 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation. RESULTS: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients 5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients. CONCLUSION: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients.

Trauma models to identify major trauma and mortality in the prehospital setting.

BACKGROUND: Patients with major trauma might benefit from treatment in a trauma centre, but early identification of major trauma (Injury Severity Score (ISS) over 15) remains difficult. The aim of this study was to undertake an external validation of existing prognostic models for injured patients to assess their ability to predict mortality and major trauma in the prehospital setting. METHODS: Prognostic models were identified through a systematic literature search up to October 2017. Injured patients transported by Emergency Medical Services to an English hospital from the Trauma Audit and Research Network between 2013 and 2016 were included. Outcome measures were major trauma (ISS over 15) and in-hospital mortality. The performance of the models was assessed in terms of discrimination (concordance index, C-statistic) and net benefit to assess the clinical usefulness. RESULTS: A total of 154 476 patients were included to validate six previously proposed prediction models. Discriminative ability ranged from a C-statistic value of 0·602 (95 per cent c.i. 0·596 to 0·608) for the Mechanism, Glasgow Coma Scale, Age and Arterial Pressure model to 0·793 (0·789 to 0·797) for the modified Rapid Emergency Medicine Score (mREMS) in predicting in-hospital mortality (11 882 patients). Major trauma was identified in 52 818 patients, with discrimination from a C-statistic value of 0·589 (0·586 to 0·592) for mREMS to 0·735 (0·733 to 0·737) for the Kampala Trauma Score in predicting major trauma. None of the prediction models met acceptable undertriage and overtriage rates. CONCLUSION: Currently available prehospital trauma models perform reasonably in predicting in-hospital mortality, but are inadequate in identifying patients with major trauma. Future research should focus on which patients would benefit from treatment in a major trauma centre.

ANTECEDENTES: Los pacientes con traumatismo mayor pueden beneficiarse del tratamiento en un centro de trauma, pero la identificación precoz del traumatismo mayor (Injury Severity Score, ISS > 15) sigue siendo difícil. El objetivo de este estudio fue validar externamente los modelos pronósticos existentes para los pacientes con traumatismos con el fin de evaluar su capacidad para predecir el traumatismo mayor y la mortalidad en el entorno pre-hospitalario. MÉTODOS: Los modelos pronóstico se identificaron mediante una búsqueda sistemática de la literatura hasta octubre de 2017. Los pacientes incluidos fueron pacientes con traumatismos que fueron trasladados mediante los servicios de emergencia médica (emergency medical services, EMS) a un hospital inglés perteneciente a Trauma Audit and Research Network (TARN) entre 2013 y 2016. Las variables evaluadas fueron los traumatismos graves (ISS > 15) y la mortalidad hospitalaria. El rendimiento de los modelos se analizó en términos de discriminación (índice de concordancia, c) y de beneficio neto para evaluar la utilidad clínica. RESULTADOS: Se incluyeron un total de 154.476 pacientes para validar los seis modelos de predicción propuestos previamente. La capacidad discriminatoria osciló entre c = 0,602 (i.c. del 95%: 0,596-0,608) para el modelo que incluye mecanismo, escala de coma de Glasgow, edad y presión arterial (MGAP) hasta c = 0,793 (0,789-0,797) para la puntuación de medicina de emergencia rápida modificada (mREMS) en la predicción de la mortalidad hospitalaria (n = 11.882). Se identificó un traumatismo mayor en 52.818 pacientes, con una discriminación de c = 0,589 (0,586-0,592) para mREMS a c = 0,735 (0,733-0,737) para la puntuación de trauma de Kampala en la predicción de traumatismo mayor. Ninguno de los modelos de predicción cumplió con las tasas aceptables de subtriaje (undertriage) y sobretriaje (overtriage). CONCLUSIÓN: Los modelos de trauma pre-hospitalarios actualmente disponibles tienen un rendimiento razonable para predecir la mortalidad hospitalaria, pero son inadecuados para identificar a los pacientes con traumatismo mayor. En el futuro, las investigaciones deberían centrarse en identificar a los pacientes que se podrían beneficiar del tratamiento en un centro de trauma especializado.

Emergency Department visits due to intoxications in a Dutch university hospital: Occurrence, characteristics and health care costs.

BACKGROUND: Intoxications with alcohol and drugs are common in the Emergency Department. This study aimed to describe the occurrence and characteristics of intoxications (alcohol, Drugs of Abuse (DOA), pharmaceutical and chemical) presented to the Emergency Department and the health care costs of these intoxications. METHODS: This was a retrospective medical record study of all patients (≥ 16 years) who presented to the Emergency Department of an inner-city academic hospital in the Netherlands due to single or multiple intoxication(s) as the primary or secondary reason in the year 2016. An intoxication was reported as present if the attending physician described the intoxication in the patient's medical record. RESULTS: A total of 783 patients were included, accounting for 3.2% of the adult Emergency Department population (age ≥ 16 year). In 30% more than one substance was used. Intoxications with alcohol, Drugs of Abuse and pharmaceuticals was reported in respectively 62%, 29% and 21% of the intoxicated patients. The mean costs per patient presenting with an intoxication to the Emergency Department was € 1,490. The mean costs per patient were highest for pharmaceutical intoxications (€ 2,980), followed by Drugs of Abuse (€ 1,140) and alcohol (€ 1,070). CONCLUSIONS: Intoxications among patients aged 16 years and older are frequently seen at the Emergency Department and are frequently caused by multiple substances. Alcohol is the most common intoxication. Substantial healthcare costs are involved. Therefore, this study suggests that further research into hazardous alcohol consumption and DOA abuse is warranted.

Waterpipe smoking: not as innocent as it may seem.

INTRODUCTION: Waterpipe (hookah) smoking is popular; in Dutch surveys, 26% of the respondents have smoked a waterpipe at least once. However, waterpipe smoking is not without risk. We present a series of carbon monoxide (CO) poisonings after waterpipe smoking and discuss the etiology and treatment of CO intoxication after waterpipe smoking. CASE DESCRIPTIONS: We present three patients who presented with syncopial episodes and a variety of other neurological and circulatory symptoms after smoking a waterpipe. All patients had significantly elevated carboxyhaemoglobin levels (26%, 19% and 26%). Patients were treated with oxygen, following Dutch guidelines; one patient was admitted for eight hours of oxygen therapy. The other two patients were observed shortly, diverging from the guidelines because symptoms passed and the carboxyhaemoglobin normalised. DISCUSSION: Reviewing combustion chemistry, the formation of CO is a logical consequence of using burning coals as a heat source. This is due to CO2 reduction with carbon. This chemical process has not previously been related to waterpipe smoking. Dutch guidelines advise eight hours of oxygen therapy. The research this guideline is based on, justifies therapy directed at symptom relief and carboxyhaemoglobin normalisation. This strategy may prevent unnecessary hospital admissions and exposure to high-dose oxygen. CONCLUSION: We described three cases of CO intoxication after waterpipe smoking and argue why this may not be an incidental finding. Greater awareness of this risk is urgently needed. We conclude that the literature does not firmly support a fixed treatment duration.

Urinary tract infections in a university hospital: pathogens and antibiotic susceptibility.

BACKGROUND: A substantial group of patients visit the emergency department (ED) with complaints of urinary tract infections (UTI). Treatment advice is based on national and local public health surveillance data. It is unclear whether this advice is adequate for hospitals with selected patient populations, such as university hospitals. METHODS: We performed a retrospective study on patients visiting the ED of the Erasmus University Medical Center (Erasmus MC) in the Netherlands from January 1st, 2013 until December 31st, 2014 with a suspected complicated UTI (cUTI) and positive urinary cultures. Patient data, data concerning the ED visit and microbiological data were analysed. RESULTS: 439 patients visited the ED, of whom 429 had a cUTI. Our results were compared with NethMap data. Distribution of uropathogens was comparable with the overall distribution in the Netherlands. Antibiotic susceptibility was comparable for intravenous antibiotics, but was lower for oral antibiotics. Susceptibility for empiric antibiotic therapy (i.e., cefuroxime and gentamyicin) was 96.2%. Pathogens differed from the index culture in 56.2% 104/185) of the urinary cultures available from the previous year. Using logistic regression, we found that a shorter time between last admission to the initiated antibiotic regimen was associated with lower susceptibility of cultured uropathogens. CONCLUSION: The distribution and antibiotic susceptibility of uropathogens for intravenous antibiotics in a Dutch university hospital is comparable with overall distribution in the Netherlands. Empiric antibiotic therapy in our local guideline appears to be an adequate antibiotic regimen for cUTI and we therefore recommend treating patients accordingly. Extension of the chosen regimen based on earlier cultured pathogens is advised, and narrowing of the antibiotic regimen strongly discouraged.

Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study.

OBJECTIVES: The aim was to effectively reduce the unnecessary use of broad spectrum antibiotics in the emergency department (ED), patients with bacterial infections need to be identified accurately. We investigated the diagnostic value of a combination of biomarkers for bacterial infections, C-reactive protein (CRP), and procalcitonin (PCT), together with biomarkers for viral infections, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and interferon-gamma-induced protein-10 (IP-10), in identifying suspected and confirmed bacterial infections in a general ED population with fever. METHODS: This is a sub-study in the HiTEMP cohort. Patients with fever were included during ED triage, and blood samples were obtained. Using both diagnostics and expert panel analysis, all patients were classified as having either suspected or confirmed bacterial infections, or non-bacterial disease. Using multivariable logistic regression analysis, three biomarker models were analysed: model 1, CRP, TRAIL, IP-10; model 2, PCT, TRAIL, IP-10; and model 3, CRP, PCT, TRAIL, IP-10. RESULTS: A total of 315 patients were included, of whom 228 patients had a suspected or confirmed bacterial infection. The areas under the curve for the combined models were the following: model 1, 0.730 (95% CI 0.665-0.795); model 2, 0.748 (95% CI 0.685-0.811); and model 3, 0.767(95% CI 0.704-0.829). CONCLUSIONS: These findings show that a combination of CRP, PCT, TRAIL and IP-10 can identify bacterial infections with higher accuracy than single biomarkers and combinations of a single bacterial biomarkers combined with TRAIL and IP-10.

Optimization of the APOP screener to predict functional decline or mortality in older emergency department patients: Cross-validation in four prospective cohorts.

INTRODUCTION: Many screening instruments to predict adverse health outcomes in older patients visiting the emergency department (ED) have been developed, but successful implementation has been hampered because they are insufficiently validated or not tailored for the intended use of everyday clinical practice. The present study aims to refine and validate an existing screening instrument (the APOP screener) to predict 90-day functional decline or mortality in older ED patients. METHODS: Consecutive older patients (≥70 years) visiting the EDs of four hospitals were included and prospectively followed. First, an expert panel used predefined criteria to decide which independent predictors (including demographics, illness severity and geriatric parameters) were suitable for refinement of the model predicting functional decline or mortality after 90 days. Second, the model was cross-validated in all four hospitals and predictive performance was assessed. Additionally, a pilot study among triage nurses experiences and clinical usability of the APOP screener was conducted. RESULTS: In total 2629 older patients were included, with a median age of 79 years (IQR 74-84). After 90 days 805 patients (30.6%) experienced functional decline or mortality. The refined prediction model included age, gender, way of arrival, need of regular help, need help in bathing/showering, hospitalization the prior six months and impaired cognition. Calibration was good and cross-validation was successful with a pooled area under the curve of 0.71 (0.69-0.73). In the top 20% patients predicted to be at highest risk in total 58% (95%CI 54%-62%) experienced functional decline or mortality. Triage nurses found the screener well suited for clinical use, with room for improvement. CONCLUSION: In conclusion, optimization of the APOP screener resulted in a short and more simplified screener, which adequately identifies older ED patients at highest risk for functional decline or mortality. The findings of the pilot study were promising for clinical use.

Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study).

OBJECTIVES: Overuse of broad-spectrum antibiotics in emergency departments (EDs) results in antibiotic resistance. We determined whether procalcitonin (PCT) -guided therapy can be used to reduce antibiotic regimens in EDs by investigating efficacy, safety and accuracy. METHODS: This was a non-inferiority multicentre randomized clinical trial, performed in two Dutch hospitals. Adult patients with fever ≥38.2°C (100.8°F) in triage were randomized between standard diagnostic workup (control group) and PCT-guided therapy, defined as standard workup with the addition of one single PCT measurement. The treatment algorithm encouraged withholding antibiotic regimens with PCT <0.5 µg/L, and starting antibiotic regimens at PCT ≥0.5 µg/L. Exclusion criteria were immunocompromised conditions, pregnancy, moribund patients, patients <72 h after surgery or requiring primary surgical intervention. Primary outcomes were efficacy, defined as number of prescribed antibiotic regimens; safety, defined as combined safety end point consisting of 30 days mortality, intensive-care unit admission, ED return visit within 2 weeks; accuracy, defined as sensitivity, specificity and area-under-the-curve (AUC) of PCT for bacterial infections. Non-inferiority margin for safety outcome was 7.5%. RESULTS: Between August 2014 and January 2017, 551 individuals were included. In the PCT-guided group (n = 275) 200 (73%) patients were prescribed antibiotic regimens, in the control group (n = 276) 212 (77%) patients were prescribed antibiotics (p 0.28). There was no significant difference in combined safety end point between the PCT-guided group, 29 (11%), and control group, 46 (16%) (p 0.16), with a non-inferiority margin of 0.46% (n = 526). AUC for confirmed bacterial infections for PCT was 0.681 (95% CI 0.633-0.730), and for CRP was 0.619 (95% CI 0.569-0.669). CONCLUSIONS: PCT-guided therapy was non-inferior in terms of safety, but did not reduce prescription of antibiotic regimens in an ED population with fever. In this heterogeneous population, the accuracy of PCT in diagnosing bacterial infections was poor. TRIAL REGISTRATION IN NETHERLANDS TRIAL REGISTER: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4949.

Non-targeted HIV screening in emergency departments in the Netherlands.

BACKGROUND: In the Netherlands a substantial proportion of newly diagnosed human immunodeficiency virus (HIV) patients present late for care and an estimated 12-34% of people living with HIV are undiagnosed. Linkage to care of these patients is important to decrease HIV transmission and to improve individual patient outcomes. We investigated if non-targeted HIV testing in emergency departments is a useful and cost-effective way to identify these patients. METHODS: In a cross-sectional multicentre study, eligible adult patients who underwent phlebotomy were given an active choice to be additionally tested for HIV. In a subset of patients, risk factors for HIV infection were asked for. A cost-effectiveness analysis was conducted. RESULTS: Of 7577 eligible patients, 3223 patients were tested, and two new HIV infections were diagnosed (0.06%). Both patients had risk factors for HIV infection. Non-targeted HIV testing in the emergency department was not considered cost-effective, with a cost per quality adjusted life years gained of € 77,050, more than triple the Dutch cost-effectiveness threshold of € 20,000. CONCLUSION: Non-targeted HIV testing in emergency departments in the Netherlands had a low yield of newly diagnosed HIV infections and was not cost-effective. Our data suggest that targeted HIV testing may offer an alternative approach to decrease the number of undiagnosed people living with HIV.

Microbiological outcomes and antibiotic overuse in Emergency Department patients with suspected sepsis.

OBJECTIVE: To study the presence of bacterial disease and antibiotic use in patients in the emergency department (ED) included in the local sepsis protocol. METHODS: An observational retrospective cohort study. Adults aged > 18 years, presenting to the ED of a large teaching hospital, from 1 January to 1 June 2011, with more than two SIRS criteria and a clinical suspicion of sepsis were included. RESULTS: Bacterial disease was suspected or confirmed in only 71% of all the patients with suspected sepsis (2008 definition) and consequently treated with antibiotics. Most of these patients (58%) suffered from systemic inflammatory response syndrome (SIRS) without signs of organ dysfunction, hypotension or hypoperfusion. Despite absence of bacterial disease in 29% of the patients after rigorous diagnostics, median antibiotic treatment in this group was still seven days (IQR 4-10). CONCLUSIONS: Standard sepsis detection using SIRS criteria and clinical suspicion identified patients with suspected or confirmed bacterial disease in 71% of the cases. A significant proportion of patients were exposed to prolonged antibiotic use without proof of bacterial disease. This study illustrates the difficulties in correctly identifying bacterial disease and sepsis, and shows that overuse of antibiotics may be the consequence.

Knowledge about systemic inflammatory response syndrome and sepsis: a survey among Dutch emergency department nurses.

BACKGROUND: Sepsis has a high mortality. Early recognition and timely treatment are essential for patient survival. The aim of this study is to examine the factors that influence the knowledge and recognition of systemic inflammatory response syndrome (SIRS) criteria and sepsis by emergency department (ED) nurses. METHODS: A prospective, multi-center study including 216 ED nurses from 11 hospitals and academic medical centers in The Netherlands was conducted in 2013. A validated questionnaire was used to evaluate ED nurses' knowledge about SIRS and sepsis. Questions about demographic characteristics were also included, to investigate factors that may contribute to the knowledge about SIRS and sepsis. RESULTS: The mean total score was 15.9 points, with a maximum possible score of 29 points. ED nurses employed at hospitals with a level 3 intensive care unit (ICU) scored significantly higher than their colleagues employed at hospitals with a level 1 or 2 ICU. Recently completed education in sepsis was associated with a higher score. The employees in low ICU level hospitals who reported recent education did not score significantly lower than their ICU level 3 colleagues. ED nurses over the age of 50 scored significantly lower than their younger colleagues. CONCLUSIONS: The knowledge of ED nurses concerning SIRS and sepsis rises proportionally with the level of ICU in hospitals. Recent education in sepsis raises knowledge level as well. We recommend that when there is a low exposure rate to SIRS and sepsis, more emphasis should be placed on regular education.

A 45-year-old woman with an anticholinergic toxidrome.

Intentional or accidental intoxications are common in the emergency department, but are not always sufficiently recognised. When intoxication is suspected, the causative agent or combination of agents often remain unclear, making these patients a diagnostic challenge. We present here a 45-year-old woman who was admitted due to altered consciousness. The clinical presentation fitted the anticholinergic toxidrome and an intoxication with venlafaxine (her known prescribed medication) was suspected. Plasma venlafaxine concentrations, however, were very low. After 24 hours the patient recovered completely. Further testing after discharge revealed high concentrations of promethazine, confirming the suspected diagnosis. This case illustrates the importance of knowledge of toxidromes and good collaboration with the hospital pharmacist. Because of the thorough testing the patient could receive proper treatment.

Unintentional nutmeg autointoxication.

Nutmeg ingestion in large amounts can cause toxic symptoms such as hallucinations, tachycardia and anticholinergic effects. We describe a case of a 37-year-old woman who experienced an unintentional autointoxication of nutmeg. It is likely that nutmeg intoxication is underreported. We suggest to specifically think of nutmeg ingestion in case of symptoms as mentioned above.

Variations in estrogen receptor alpha gene and risk of dementia, and brain volumes on MRI.

The role of estrogens in Alzheimer's disease (AD) is controversial. We investigated the association between well-recognized, and potentially functional, polymorphisms in the estrogen receptor (ER) alpha gene and the risk of AD in a prospective study of 6056 Caucasian older men and women aged 55 years and over. In a subset of 468 participants, we assessed volumes of the hippocampus and amygdala, which have a high density of ER alpha, with brain magnetic resonance imaging (MRI) (1.5 T MR unit). During a total of 35 405 person-years of follow-up (mean per persons 5.8 years), 312 new cases of dementia were detected, of whom 230 were diagnosed with AD. Neither the PvuII nor the XbaI polymorphism or haplotypes thereof were associated with the risk of all-cause dementia or AD. In contrast, we found that nondemented women who carried the PvuII p allele or haplotype 'px' had smaller amygdalar volumes on MRI in an allele-dose-dependent fashion. Total amygdalar volume was 4.50 (SE 0.10) in PP genotype, 4.45 (SE 0.06) in Pp genotype, and 4.18 ml (SE 0.08) in pp genotype (P trend=0.008). Further studies are required to investigate whether this smaller amygdalar volume has functional significance.

Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study.

The incidence of all non-vertebral fractures, as well as the relation to bone mineral density (BMD), was quantified in 7806 men and women from the Rotterdam Study, a prospective, population-based cohort study of men and women aged 55 years and older. In addition, the sensitivity of using a T-score at or below -2.5 for identifying subjects at risk for fractures was assessed. At baseline, between 1990 and 1993, femoral neck BMD was measured by dual energy X-ray absorptiometry (DXA). Subsequently, gender-specific T-scores were calculated using the NHANES reference population. During a mean follow-up of 6.8 years, information on incident non-vertebral fractures was gathered. In general, hip, wrist and upper humerus fractures are the most frequent fractures in both men and women. Femoral neck BMD appears to be an equally important risk factor in both genders, and is especially related to hip fractures. For all non-vertebral fractures, the age-adjusted hazard ratio (95% confidence interval) per standard deviation decrease in femoral neck BMD was 1.5 (1.4-1.6) for women and 1.4 (1.2-1.6) for men. For hip fractures, the hazard ratios were 2.1 (1.7-2.5) for women and 2.3 (1.6-3.3) for men. Only 44% of all non-vertebral fractures occurred in women with a T-score below -2.5; in men, this percentage was even lower (21%). Thus, there is a clear need for the development of more sensitive risk assessment tools, using not only BMD, but also other clinical predictors of fractures.