Age-dependent physiological changes, medicines and sex-influenced types of falls

Background/Study context: We investigated various parameters related to falls including age-dependent physiological changes, regular medicine use and different types of falls experienced. There is a lack of research investigating the impact of health status, sex, polypharmacy and ageing on different types of falls such as unspecified fall on the same level, mechanical fall on the same level relating to slipping, tripping or loosing balance, fall from a chair, vehicle and fall as a result of syncope, fall from steps or stairs and fall from the height. METHODS: The study included a random sample of 250 older patients, which comprised 10% of the total number of patients (n = 2,492), admitted to a large-scale academic hospital following a fall. Patients' medicine and illness history, types of falls, liver, renal and sensory function were collected. Univariate analysis was used to examine associations between the type of fall and explanatory variables, followed by multinominal logistic regression analysis. RESULTS: There was a significant association between the type of fall and sex, p = 0.01, and between the type of fall and regular medicine use, p = 0.002. The multinominal logistic regression analysis revealed that the full model, which considered all explanatory variables together, was statistically significant, p < 0.001. The strongest predictor of all types of falls except 'fall from the height' was female sex followed by the regular medicine use. CONCLUSION: This study identified predictors for various types of falls in older people; the strongest predictor being a female sex followed by regular medicine use. Based on these findings, the medicine prescribing practice in this older population must be carefully reviewed

Testing the validity, reliability and utility of the Self-Administration of Medication (SAM) tool in patients undergoing rehabilitation.

Determination of patients\u27 ability to self-administer medications in the hospital has largely been determined using the subjective judgment of health professionals

Use of the Screening Tool of Older Persons\u27 Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) in hospitalised older people

To determine the prevalence and nature of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) in patients aged 65 years and over

A two-tiered unsupervised clustering approach for drug repositioning through heterogeneous data integration

BACKGROUND: Drug repositioning is the process of identifying new uses for existing drugs. Computational drug repositioning methods can reduce the time, costs and risks of drug development by automating the analysis of the relationships in pharmacology networks. Pharmacology networks are large and heterogeneous. Clustering drugs into small groups can simplify large pharmacology networks, these subgroups can also be used as a starting point for repositioning drugs. In this paper, we propose a two-tiered drug-centric unsupervised clustering approach for drug repositioning, integrating heterogeneous drug data profiles: drug-chemical, drug-disease, drug-gene, drug-protein and drug-side effect relationships. RESULTS: The proposed drug repositioning approach is threefold; (i) clustering drugs based on their homogeneous profiles using the Growing Self Organizing Map (GSOM); (ii) clustering drugs based on drug-drug relation matrices based on the previous step, considering three state-of-the-art graph clustering methods; and (iii) inferring drug repositioning candidates and assigning a confidence value for each identified candidate. In this paper, we compare our two-tiered clustering approach against two existing heterogeneous data integration approaches with reference to the Anatomical Therapeutic Chemical (ATC) classification, using GSOM. Our approach yields Normalized Mutual Information (NMI) and Standardized Mutual Information (SMI) of 0.66 and 36.11, respectively, while the two existing methods yield NMI of 0.60 and 0.64 and SMI of 22.26 and 33.59. Moreover, the two existing approaches failed to produce useful cluster separations when using graph clustering algorithms while our approach is able to identify useful clusters for drug repositioning. Furthermore, we provide clinical evidence for four predicted results (Chlorthalidone, Indomethacin, Metformin and Thioridazine) to support that our proposed approach can be reliably used to infer ATC code and drug repositioning. CONCLUSION: The proposed two-tiered unsupervised clustering approach is suitable for drug clustering and enables heterogeneous data integration. It also enables identifying reliable repositioning drug candidates with reference to ATC therapeutic classification. The repositioning drug candidates identified consistently by multiple clustering algorithms and with high confidence have a higher possibility of being effective repositioning candidates

The effect of 17 beta-estradiol on maternal immune activation-induced changes in prepulse inhibition and dopamine receptor and transporter binding in female rats

Maternal immune activation (MIA) during pregnancy is associated with an increased risk of development of schizophrenia in later life. 17β-estradiol treatment may improve schizophrenia symptoms, but little is known about its efficacy on MIA-induced psychosis-like behavioural deficits in animals. Therefore, in this study we used the poly(I:C) neurodevelopmental model of schizophrenia to examine whether MIA-induced psychosis-like behavioural and neurochemical changes can be attenuated by chronic treatment (2-6 weeks) with 17β-estradiol. Pregnant rats were treated with saline or the viral mimetic, poly(I:C), on gestational day 15 and adult female offspring were tested for changes in prepulse inhibition (PPI) and density of dopamine D1 and D2 receptors and dopamine transporters in the forebrain compared to control offspring. Poly(I:C)-treated offspring exhibited significantly disrupted PPI, an effect which was reversed by chronic treatment with 17β-estradiol. In control offspring, but not poly(I:C) offspring, PPI was significantly reduced by acute treatment with either the dopamine D1/D2 receptor agonist, apomorphine, or dopamine releaser, methamphetamine. 17β-estradiol restored the effect of apomorphine, but not methamphetamine, on PPI in poly(I:C) offspring. There was a strong trend for a dopamine D2 receptor binding density increase in the nucleus accumbens core region in poly(I:C) offspring, and this was reversed by chronic 17β-estradiol treatment. No changes were found in the nucleus accumbens shell, caudate putamen or frontal cortex or in the density of dopamine D1 receptors or transporters. These findings suggest that 17β-estradiol may improve some symptoms of schizophrenia, an effect that may be mediated by selective changes in dopamine D2 receptor density

Use of the Screening tool of older person\u27s prescriptions (STOPP) in older people admitted to an Australian hospital

Aims: To determine the prevalence of potentially inappropriate medications (PIMs) in older people aged 65years and over who were admitted to hospital, and to examine the medications and medication classes that comprised these PIMs with use of the Screening Tool of Older Person\u27s Prescriptions. Method: Using a retrospective clinical audit design, the medical records of 100 older patients were randomly selected and examined for the prevalence and characteristics of PIMs. The audit was undertaken of patients admitted over a 12-month period to an Australian public teaching hospital. Results: In total, 92 individual occurrences of PIMs were detected, and 54 patients had at least one PIM. The most common type of PIM experienced related to prescribed medications that adversely affected individuals who were prone to falls. Conclusion: Many older patients experienced a PIM during their hospital admission, where the risk of an adverse event could outweigh the clinical benefit

The impact of removal of ovarian hormones on cholinergic muscarinic receptors:Examining prepulse inhibition and receptor binding

Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [3H]-pirenzepine, [3H]-AF-DX, and [3H]-4-DAMP, to label M1, M2/M4, and M3 receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density