Age modifies the association between apathy and recurrent falling in Dutch ambulant older persons with a high fall risk: Recurrent falling in Dutch outpatients, does apathy play a role?

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number of falls in the past 12 months in 243 outpatients aged ≥65 years with ≥3 fall risk-factors visiting a fall-clinic after a fall. We calculated Odds Ratio's (ORs), Incidence Rate Ratio's (IRRs) and their 95% Confidential Intervals (CI95) using multivariable regression and negative binomial regression analyses. We adjusted for cognitive functioning, depression, the use of fall risk increasing drugs, visual impairment, urine incontinence, comorbidity, smoking, use of alcohol, body mass index (BMI), and the number of months between assessment of fall risk and of apathy. We assessed effect modification by age and gender. In our study, apathy was independently associated with recurrent falling in patients aged 65-75 years: OR 2.8 (CI95 1.0-7.7). Overall, patients with apathy experienced 1.46 times as many falls in the past 12 months compared to patients without apathy (IRR 1.46 (CI95 1.0-2.1). To conclude, in high fall-risk older outpatients, apathy was cross-sectionally associated with recurrent falling in patients aged 65-75 years and the number of falls. Apathy appeared to be especially relevant in relation to falling in this age group. Whether apathy predicts recurrent falling is yet to be determined.

[Systematic review of the side effects of benzodiazepines]. / Aandacht voor bijwerkingen van benzodiazepinen is belangrijk: een systematisch overzicht.

- Benzodiazepines are used frequently, despite the risk of severe side effects.- The Generic module 'Side effects; prevention, monitoring and treatment of side effects of drugs for psychiatric disorders' will be published soon. This contains recommendations for reduction in the risk for falls and fractures, cognitive problems and dependency related to the use of benzodiazepines or Z-drugs (zopiclone, zolpidem).- Prescribing physicians and pharmacists are compulsorily required to provide extensive information to patients on the anticipated effects and side effects of benzodiazepines, and on the limited prescription period.- A lot of information has become available from systematic literature reviews by the Benzodiazepines working group. Different benzodiazepines present similar risks of falls and fractures; higher doses present a higher risk, and Z-drugs are no safer.- In comparison with placebo, benzodiazepines and Z-drugs soon cause cognitive problems, even at low doses and in drugs with a short half-life. There is almost no development of tolerance for these cognitive problems.- Tailored patient education letters for ceasing benzodiazepine use are more effective than the standard letters. Different dose-tapering schemes have comparable success rates (on average 50%). Augmentation with cognitive behavioural therapy is effective for dose reduction.- It is therefore important to carefully consider the use of benzodiazepines before using them.

Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF-α experience to oncology.

Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM.

False positive acetaminophen concentrations in icteric serum.

INTRODUCTION: Serum concentrations of acetaminophen are measured to predict the risk of hepatotoxicity in cases of acetaminophen overdose and to identify acetaminophen use in patients with acute liver injury without a known cause. The acetaminophen concentration determines if treatment with N-acetyl cysteine, the antidote for acetaminophen poisoning, is warranted. DESCRIPTION: A 49-year-old woman was admitted to our hospital with a hepatic encephalopathy and a total serum bilirubin concentration of 442 µmol/l. The acetaminophen concentration of 11.5 mg/l was measured with an enzymatic-colorimetric assay, thus treatment with N-acetyl cysteine was started. Interestingly, the acetaminophen concentration remained unchanged (11.5-12.3 mg/l) during a period of 4 consecutive days. In contrast, the acetaminophen concentration measured by HPLC, a chromatographic technique, remained undetectable. DISCUSSION: In the presented case, elevated bilirubin was the most likely candidate to interfere with acetaminophen assay causing false positive results. Bilirubin has intense absorbance in the ultraviolet and visible regions of the electromagnetic spectrum and for that reason it causes interference in an enzymatic-colorimetric assay. CONCLUSION: False positive acetaminophen laboratory test results may be found in icteric serum, when enzymatic-colorimetric assays are used for determination of an acetaminophen concentration. Questionable acetaminophen results in icteric serum should be confirmed by a non-enzymatic method, by means of ultrafiltration of the serum, or by dilution studies.

The relation between granule size, granule stickiness, and torque in the high-shear granulation process.

PURPOSE: To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. METHODS: Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipulation. Surface properties of wet granules were manipulated by coating them with talc. RESULTS: The torque-granule size relationship could not be explained by the rise in mass of the individual granules; it occurs rather through an increase in stickiness of the granules when the moisture content is increased. Obviously, the increased stickiness that causes the granules to grow also increases the torque. Increased stickiness was shown to be the result of an increased deformability of the granules at higher moisture contents, in combination with a change in surface properties. The elastic-plastic behavior (ratio of elastic to plastic deformation) was found to change at increasing moisture contents. CONCLUSIONS: Our results imply that changes in the stickiness of the granular material that may be caused by changes in composition shift the torque-size relationship. This may be of particular importance when, for example, granulation results from placebo batches are used to predict the granule size of drug-containing batches.

The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation.

The structure of granules changes during the high shear granulation process. The purpose of this research was to investigate the effect of the amount of binder liquid on the structure of the granules and the structural changes which occur during the granulation process, using microcrystalline cellulose (MCC) and water as the model system. The structure is the result of the granulation mechanism; therefore, conclusions can be drawn about the latter by studying the former. X-ray microtomography and scanning electron microscopy (SEM) were applied in order to visualise the densification process of granules, which were first freeze dried in order to preserve their structure. Variations in their porosity were quantified by applying image analysis to the tomography results. In order to link the granule mechanical properties to their structural differences, a micromanipulation technique was used to measure granule resistance to deformation. MCC granules granulated with 100% (w/w) water showed increased densification with time, as expected; detailed examination showed that densification is more pronounced in the core of the granule; whereas the outer part remained more porous. Increased densification reduces deformability, so that granules become more resistant to breakage. The lower deformability of the densified granules in the final stages of granulation might result in establishment of equilibrium between attrition and growth, without substantial gross breakage. On the other hand, when more water was used (125%, w/w), densification was hardly observed; the porosity of the granule core was still high even after prolonged granulation times. This may be explained by the fact that higher water content increases the ease of deformation of granules. This increased deformability led to significant granule breakage even during the final phases of the granulation process. Therefore, for these granules a final equilibrium between breakage and coalescence might be established. This also explains why more granules produced with 125% granulation liquid were composed of fragments of irregular shape. Our results establish the link between the granulation behaviour of MCC in the latter stages and the material structure of these granules, which is determined by their liquid content. The process conditions (amount of liquid) to be chosen depend largely on the final purpose for which the granular material is produced.