Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats.

Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.

Investigation of interventions to reduce nurses' medication errors in adult intensive care units: A systematic review.

BACKGROUND: Medication errors in adult intensive care units (ICUs) are both frequent and harmful. For nurses, these errors may be multifactorial and multidisciplinary, extending from prescription stage to monitoring of patient response to medication. Therefore, diverse interventions have been developed to optimise the medication process to prevent such errors. OBJECTIVES: The objective of this systematic review was to identify research investigating interventions that may be effective in reducing the rate of nurses' medication errors in adult ICUs. METHODS: A systematic search was undertaken of three databases: Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, and EMCARE using a combination of key terms related to "medication errors", "nurses", "interventions", and "intensive care units". The search was limited to studies published in English between 2009 and 2019. Independent screening, quality appraisal, and data extraction were undertaken by two reviewers. RESULTS: A total of 464 records were identified from database searches. Eleven studies met inclusion criteria: ten were quasi-experimental designs and one was a randomised controlled trial. Studies examined six types of interventions: prefilled syringes, barcode-assisted medication administration, an automated dispensing system, nursing education programs, a protocolised program logic form, and a preventive interventions program with protocols and pharmacist-supported supervision and monitoring. Findings revealed that a prefilled syringe, nurses' education programs, and the protocolised program logic form were most effective in reducing medication errors. For the barcode-assisted medication administration, automated dispensing systems, and a preventive interventions program with protocols and pharmacist-supported supervision and monitoring, results showed wide variability in effectiveness. CONCLUSION: This review found that the evidence for effective interventions to reduce nurses' medication errors in adult ICUs is limited, due largely to inconsistencies in research design and methods. Therefore, further studies such as randomised controlled trials focusing on a single intervention are required to provide robust evidence of the effectiveness of interventions.

Interventions to reduce medication errors in adult medical and surgical settings: a systematic review.

BACKGROUND AND AIMS: Medication errors occur at any point of the medication management process, and are a major cause of death and harm globally. The objective of this review was to compare the effectiveness of different interventions in reducing prescribing, dispensing and administration medication errors in acute medical and surgical settings. METHODS: The protocol for this systematic review was registered in PROSPERO (CRD42019124587). The library databases, MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched from inception to February 2019. Studies were included if they involved testing of an intervention aimed at reducing medication errors in adult, acute medical or surgical settings. Meta-analyses were performed to examine the effectiveness of intervention types. RESULTS: A total of 34 articles were included with 12 intervention types identified. Meta-analysis showed that prescribing errors were reduced by pharmacist-led medication reconciliation, computerised medication reconciliation, pharmacist partnership, prescriber education, medication reconciliation by trained mentors and computerised physician order entry (CPOE) as single interventions. Medication administration errors were reduced by CPOE and the use of an automated drug distribution system as single interventions. Combined interventions were also found to be effective in reducing prescribing or administration medication errors. No interventions were found to reduce dispensing error rates. Most studies were conducted at single-site hospitals, with chart review being the most common method for collecting medication error data. Clinical significance of interventions was examined in 21 studies. Since many studies were conducted in a pre-post format, future studies should include a concurrent control group. CONCLUSION: The systematic review identified a number of single and combined intervention types that were effective in reducing medication errors, which clinicians and policymakers could consider for implementation in medical and surgical settings. New directions for future research should examine interdisciplinary collaborative approaches comprising physicians, pharmacists and nurses. LAY SUMMARY: Activities to reduce medication errors in adult medical and surgical hospital areas. INTRODUCTION: Medication errors or mistakes may happen at any time in hospital, and they are a major reason for death and harm around the world. OBJECTIVE: To compare the effectiveness of different activities in reducing medication errors occurring with prescribing, giving and supplying medications in adult medical and surgical settings in hospital. METHODS: Six library databases were examined from the time they were developed to February 2019. Studies were included if they involved testing of an activity aimed at reducing medication errors in adult medical and surgical settings in hospital. Statistical analysis was used to look at the success of different types of activities. RESULTS: A total of 34 studies were included with 12 activity types identified. Statistical analysis showed that prescribing errors were reduced by pharmacists matching medications, computers matching medications, partnerships with pharmacists, prescriber education, medication matching by trained physicians, and computerised physician order entry (CPOE). Medication-giving errors were reduced by the use of CPOE and an automated medication distribution system. The combination of different activity types were also shown to be successful in reducing prescribing or medication-giving errors. No activities were found to be successful in reducing errors relating to supplying medications. Most studies were conducted at one hospital with reviewing patient charts being the most common way for collecting information about medication errors. In 21 out of 34 articles, researchers examined the effect of activity types on patient harm caused by medication errors. Many studies did not involve the use of a control group that does not receive the activity. CONCLUSION: A number of activity types were shown to be successful in reducing prescribing and medication-giving errors. New directions for future research should examine activities comprising health professionals working together.

Medication-based Refill Adherence Among Pregnant Women Living With HIV in Nigeria.

PURPOSE: A major global public health challenge is the continuance of new pediatric HIV infections primarily because of mother to child transmission of HIV occurring mainly in sub-Saharan African countries. The purpose of this study was to examine antiretroviral therapy (ART) refill adherence and its determinants among pregnant women living with HIV in Nigeria. METHODS: A retrospective review of pharmacy refill records was undertaken to examine adherence data on 275 pregnant women undergoing ART in 4 high-volume HIV treatment sites in Nigeria. A pharmacy refill adherence measure was used to assess medication refill behavior of pregnant women living with HIV who had received an ART refill during a period of 3 months. Medication-based ART refill adherence was categorized as % adherence (100% adherence) or % nonadherence (<100% adherence) to the ART refill scheduled dates. Refill appointments were scheduled on a 28-day cycle. Multivariable logistic regression analysis was performed. FINDINGS: Of the 275 women, 59.3% (95% CI, 53.1%-65.5%) were adherent to their ART refill schedule. Women who initiated ART during the third trimester of their current pregnancy had the lowest adherence rate of 30.8% (95% CI, 7.7%-53.8%) compared with women who commenced ART before conception or during the first or second trimester. The availability of a treatment support person was significantly associated with ART refill adherence. The odds of medication-based refill adherence were 2.9 times higher for participants who had a treatment support person (odds ratio = 2.9; 95% CI, 1.6-5.2; p = 0.001). IMPLICATIONS: Results indicate that having a treatment support person could contribute to improving ART adherence in pregnant women living in Nigeria.

The effect of 17ß-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. 17ß-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 17ß-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 17ß-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. 17ß-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 17ß-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 17ß-estradiol may improve some symptoms of schizophrenia, an effect that may be mediated by selective changes in dopamine D2 receptor density.

Physical comorbidities in private psychiatric inpatients: Prevalence and its association with quality of life and functional impairment.

The aim of this study was to examine the association between physical health conditions and quality of life and functioning in private psychiatric inpatients. We sought to determine whether quality of life and functioning was poorer in individuals with physical comorbidity compared to those without. A quantitative correlational descriptive design was utilized. Seventy patients were included in sequential order within a week of admission to hospital. Participants completed the SF-36 survey, and the corresponding hospital records were audited. The STROBE guidelines were followed in the reporting of this research. The study found that 64.3% (45/70) of participants had one or more comorbid physical health conditions, primarily cardiovascular, respiratory, musculoskeletal, endocrine and medically unexplained conditions or syndromes. Chronic pain was experienced by 40% (28/70) of participants, and 47.6% (33/70) were found to be overweight or obese. Tobacco smoking and obesity were risk factors associated with physical comorbidity (P = 0.02 and P < 0.001, respectively). Quality of life and functioning were poorer in those with physical health conditions, particularly in the SF-36 domains of bodily pain, physical functioning and general health (P < 0.001, P = 0.003 and P = 0.005, respectively). Physical health conditions were largely prevalent, and quality of life and functioning were poorer in those with physical comorbidities. The implementation of clinical guidelines for the monitoring of physical health has been proposed as well as a dedicated physical health nursing role. Continuation of integrative programmes focusing on both physical and mental health may also benefit patients in this setting.

Perspectives of pregnant women, family members and health professionals on medication adherence in Nigeria.

ABSTRACT Nigeria has the highest burden of mother-to-child transmission of human immunodeficiency virus (HIV) worldwide. Pregnant women living with HIV in Nigeria face challenges adhering to antiretroviral therapy (ART). We explored the perspectives of pregnant women living with HIV, family members, friends and health professionals to understand adherence to ART. Pregnant women, family members, friends and health professionals recruited from four HIV treatment sites in Nigeria participated in semi-structured interviews and focus groups. Thematic analysis was conducted and themes and sub-themes were mapped against the Theory of Planned Behaviour comprising behavioural, normative and control beliefs. Overall, 74 participants took part in the study. Common behavioural beliefs comprised maintaining the mother's and unborn child's health and success of having HIV-negative children from previous pregnancies. Common normative beliefs involved partner and family support for medication taking and medication refill visits. Common control beliefs comprised fear of discrimination and stigmatisation. Results showed that adherence to ART in pregnancy is intricate. Hence, before interventions are developed to change adherence behaviours in pregnant women tailored strategies should be devised that address the salient beliefs that influence adherence during pregnancy.

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.

How do cognitive and functional impairment relate to the use of anticholinergic medications in hospitalised patients aged 65 years and over?

BACKGROUND: Anticholinergic medications are commonly prescribed to older adults despite their unfavourable pharmacological profile. There are no specific systems in place to alert prescribers about the wide range of medications with anticholinergic properties and their cumulative potential. AIMS: To examine associations between medications with anticholinergic properties and cognitive and functional impairment in hospitalised patients aged 65 years and older. METHODS: This descriptive, cross-sectional study included 94 patients admitted to a rehabilitation ward and a geriatric evaluation and management unit. Anticholinergic burden was calculated using the Anticholinergic Risk Scale. The Addenbrooke's Cognitive Examination and the Elderly Symptom Assessment Scale tools were utilised to assess cognitive function and burden of anticholinergic symptoms, respectively. RESULTS: Medications with anticholinergic properties were taken by 72.3% of patients with level 1 being the most commonly consumed (median 1, IQR = 0-2) medications. There was no association between anticholinergic medication use and cognitive function or anticholinergic symptoms. Increasing age and the hospital length of stay were associated with fewer anticholinergic symptoms (p < 0.001 and p = 0.021, respectively), whereas the total number of medications consumed was linked to a greater burden of anticholinergic symptoms (p < 0.001). CONCLUSION: A lack of association between anticholinergic medications and cognitive function could be related to duration of exposure to this group of medications and the age sensitivity. Additionally, the total number of medications consumed by patients was linked to a greater burden of anticholinergic symptoms. These findings highlight the need for improved knowledge and attentiveness when prescribing medications in general in this vulnerable population.

Factors Associated With Success in Reducing HIV Mother-to-child Transmission in Sub-Saharan Africa: Interviews With Key Stakeholders.

PURPOSE: A key global health challenge is the persistence of new pediatric HIV infections due to mother-to-child transmission (MCTC), particularly in sub-Saharan Africa. The purpose of this study was to identify the key strategies that some sub-Saharan African countries have used to successfully reduce new pediatric HIV infections. METHODS: A qualitative study utilizing semistructured interviews with key stakeholders in 6 sub-Saharan African countries (Burundi, Malawi, Mozambique, South Africa, Swaziland, and Uganda) was conducted from September 2017 to September 2018. These stakeholders were situated in the National Department of Health or in international health-funding bodies relating to the provision of the HIV/AIDS implementation program in these countries. The countries were selected based on considerable success achieved with HIV treatment in pregnant women. Audio-recorded interviews were transcribed verbatim and thematic analysis was undertaken. FINDINGS: In all, 6 interviews were conducted, and the mean time of the interviews was 62 min. There were similar numbers of men and women, and most were in the 35- to 45-year age group. Five in six were either a medical doctor or held a doctorate degree. Four in six had >10 years of experience working in the prevention of HIV (PMTCT). Four key strategies that contributed to significant reductions in pediatric HIV infection in the respective countries were identified: (1) committed political leadership; (2) support structures within the community; (3) innovation in service delivery; and (4) robust monitoring and evaluation systems. Stakeholders spoke about how their governments played a leading role in engagement with communities, and in the dissemination of services. Innovative service delivery comprising task-shifting initiatives and the integration of maternal, newborn, and child health and HIV PMCTC services played an important role in reducing the burdens experienced by women and health care workers, leading to improved health outcomes. Peer support also helped mothers to adhere to their treatment during and after pregnancy. The capacity of national programs to monitor and evaluate the PMTCT services and the importance of regular viral-load monitoring were highlighted by the stakeholders. IMPLICATIONS: These strategies can be reviewed for possible implementation by other sub-Saharan African countries as possible means of reducing new pediatric HIV infections.

Post Option B+ implementation programme in Nigeria: Determinants of adherence of antiretroviral therapy among pregnant women with HIV.

OBJECTIVE: Nigeria has the highest rate of mother to child transmission of HIV (MTCT) in the world. By 2015, all Global Plan priority countries, except Nigeria, had adopted the Option B+ programme. Nigeria finally adopted Option B+ in 2016 with full implementation reported in 2017. We examined adherence to antiretroviral therapy (ART) among pregnant women since the rollout of Option B+ in Nigeria. METHODS: A cross sectional approach was adopted that involved dissemination of a survey (Adult AIDS Clinical Trial Groups [AACTG] standardised survey) to HIV positive pregnant women, to assess adherence to ART. This study was conducted from February to June, 2018 in four health care sites in Akwa Ibom State, in the South-South region of Nigeria. Bootstrapping was used to estimate the 95% confidence interval of the prevalence of adherence. Bivariate associations between patient demographic characteristics and medication taking behaviours, and the outcome variable of ART adherence were examined using Chi-square tests. Multivariable logistic regression was used to identify factors independently associated with adherence. RESULTS: Of the 275 women (response rate=92.6%), 32.7% (95% CI: 26.9-38.5) self-reported taking all ART doses in the past 96 hours. In the multivariable logistic regression analyses, there were positive associations between an increased education level (OR=1.7, p=0.006) and disclosure of HIV status (OR=2.3, p=0.024), and medication adherence. For women who had previous prevention of MTCT exposure, the odds of medication adherence were 2.5 times higher compared with those with no previous MTCT exposure (OR=2.5, p=0.005). CONCLUSION: Adherence to ART among pregnant women in Nigeria is low. There is a need to improve adherence during pregnancy under the Option B+ programme in Nigeria.

Differential effects of chronic 17ß-oestradiol treatment on rat behaviours relevant to depression.

Sex differences are a prominent feature of the pathophysiology of psychiatric disorders, such as major depressive disorder, which affects women at a higher incidence than men. Research suggests that the most potent endogenous oestrogen, 17ß-oestradiol, may have therapeutic potential in treating depression. However, preclinical studies have produced mixed results, likely as a result of various methodological factors such as treatment duration. The present study aimed to investigate the effects of ovariectomy and chronic 17ß-oestradiol treatment via a s.c. silastic implant on behaviours relevant to depression in adult female Sprague-Dawley rats. Rats were assessed in the forced swim test, saccharin preference test and novel object recognition memory test, as well as for possible confounding behaviours, including locomotion and anxiety (open field test) and motivation and anxiety (novelty suppressed feeding test). Treatment effects were verified using body and uterus weight, as well as serum concentrations of 17ß-oestradiol, progesterone and testosterone. Compared to ovariectomised rats, chronic 17ß-oestradiol treatment enhanced saccharin preference and novel object recognition performance. There were no group differences in passive or active coping behaviour when assayed using the forced swim test. Taken together, these results support an antidepressant-like action of oestrogens but highlight that the beneficial effects of chronic 17ß-oestradiol treatment may be related to specific depression-related symptoms, particularly anhedonia and memory.

A meta-analysis of effectiveness of interventions to improve adherence in pregnant women receiving antiretroviral therapy in sub-Saharan Africa.

OBJECTIVE: We evaluated the effectiveness of interventions aimed at improving antiretroviral therapy (ART) adherence during pregnancy in sub-Saharan Africa. METHODS: For this meta-analysis, the following databases were searched: MEDLINE Complete, Embase, Global Health, CINAHL Complete, and Google Scholar. Randomized and nonrandomized studies were considered for inclusion if they involved an intervention with the intent of improving medication adherence among pregnant women taking ART in sub-Saharan Africa. Databases were searched from inception to the end of August 2017. The primary outcome assessed was adherence to ART, defined as the proportion of women adherent to treatment in the control and intervention groups. Risk ratios and random effect meta-analysis were undertaken, and heterogeneity was examined with the I2 statistic. RESULTS: The systematic search of databases yielded a total of 402 articles, of which 19 studies were selected for meta-analysis with a total of 27,974 participants. Nine types of interventions were identified in the 19 studies to improve ART adherence. The test for the subgroup differences showed that there was a statistically significant difference among the 9 subgroups of interventions, χ2 (8)=102.38; p=0.00001. Collectively, in the meta-analysis, the various intervention types made a significant impact on improving medication adherence. The overall effect estimate with 95% CI was as follows: 1.25 (95% CI=1.03, 1.52, p=0.03). The following risk ratio results for meta-analysis were obtained for the three interventions that showed significant impact on adherence; namely social support and structural support, 1.58 (95% CI=1.36, 1.84, p<0.00001); education, social support and structural support=2.60 (95% CI=1.95, 3.45, p<0.00001); and device reminder=1.13 (95% CI=1.05, 1.20, p=0.0004). The proportion of women who were adherent to ART as a result of the interventions was 59.3% compared with 22.5% in the control groups. CONCLUSION: The use of device reminder, a combination of social support and structural support, and education, social support and structural support has the potential to improve ART adherence during pregnancy. Good quality prospective observational studies and randomized control trials are needed in sub-Saharan Africa to determine the most effective interventions.

Medication adherence in pregnant women with human immunodeficiency virus receiving antiretroviral therapy in sub-Saharan Africa: a systematic review.

BACKGROUND: The use of antiretroviral therapy (ART) is a core strategy proposed by the World Health Organization in preventing mother to child transmission (MTCT) of HIV. This systematic review aimed to examine the enablers and barriers of medication adherence among HIV positive pregnant women in sub-Saharan Africa. METHODS: We used the following keywords: HIV AND (Pregnancy OR Pregnant*) AND (PMTCT OR "PMTCT Cascade" OR "Vertical Transmission" OR "Mother-to-Child") AND (Prevent OR Prevention) AND (HAART OR "Antiretroviral Therapy" OR "Triple Therapy") AND (Retention OR Concordance OR Adherence OR Compliance) to conduct electronic searches in the following databases: MEDLINE Complete (1916-Dec 2017), Embase (1947-Dec 2017), Global Health (1910-Dec 2017) and CINAHL Complete (1937-Dec 2017). Of the four databases searched, 401 studies were identified with 44 meeting the inclusion criteria. Seven studies were added after searching reference lists of included articles, resulting in 51 articles in total. RESULTS: The review demonstrated that stigma, cost of transportation, food deprivation and a woman's disclosure or non-disclosure of her HIV status to a partner, family and the community, could limit or define the extent of her adherence to prescribed antiretroviral drugs during pregnancy. Furthermore, the review indicated that knowledge of HIV status, either before or during pregnancy, was significantly associated with medication adherence. Women who knew their HIV status before pregnancy demonstrated good adherence while women who found out their HIV infection status during pregnancy were linked with non-adherence to ART. CONCLUSION: This review revealed several barriers and enablers of adherence among pregnant women taking ART in sub-Saharan Africa. Major barriers included the fear of HIV infection status disclosure to partners and family members, stigma and discrimination. A major enabler of adherence in women taking ART was women's knowledge of their HIV status prior to becoming pregnant. Enhanced effort is needed to facilitate women's knowledge of their HIV status before pregnancy to enable disease acceptance and management, and to support pregnant women and her partner and family in dealing with fear, stigma and discrimination about HIV.

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.

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.

Incidence of complications in men undergoing transurethral resection of the prostate.

Objectives: To examine the link between medication use and the risk of bleeding complications following transurethral resection of the prostate from the second postoperative day until hospital discharge. Method: Using a retrospective observational study design, the medical records of all patients who underwent transurethral resection of the prostate over a 24-month period were examined. Comprehensive data regarding patients' medication history, comorbidities and complications that occurred either during or after surgery were collected from medical records. Inferential statistical analysis was used to examine associations between demographic and medication variables and the risk of complications. Results: Complications arising after surgery occurred in 48/135 (36%) of patients. The most common complications postoperatively were hematuria, occurring in 41/48 (85%) and hematuria with clot retention, occurring in 24/48 (50%) of patients who suffered complications. There was a significant association between the number of medications prescribed and postoperative complications; for hematuria, χ2 (12) = 21.50, p = 0.04; and for hematuria with clot retention χ2 (12) = 24.97, p = 0.015. Conclusions: Demographic data relating to patients' age, comorbid state and the number of standard medications prescribed is associated with an increase in macroscopic hematuria and macroscopic hematuria with clot retention after transurethral resection of the prostate. These findings emphasize the importance of nursing practice in both preoperative and postoperative care of patients undergoing surgery. Nurses need to be very vigilant in assessing patients at risk of increased bleeding from a transurethral resection of the prostate by examining their medication regimen.

Positive-Unlabeled Learning for inferring drug interactions based on heterogeneous attributes.

BACKGROUND: Investigating and understanding drug-drug interactions (DDIs) is important in improving the effectiveness of clinical care. DDIs can occur when two or more drugs are administered together. Experimentally based DDI detection methods require a large cost and time. Hence, there is a great interest in developing efficient and useful computational methods for inferring potential DDIs. Standard binary classifiers require both positives and negatives for training. In a DDI context, drug pairs that are known to interact can serve as positives for predictive methods. But, the negatives or drug pairs that have been confirmed to have no interaction are scarce. To address this lack of negatives, we introduce a Positive-Unlabeled Learning method for inferring potential DDIs. RESULTS: The proposed method consists of three steps: i) application of Growing Self Organizing Maps to infer negatives from the unlabeled dataset; ii) using a pairwise similarity function to quantify the overlap between individual features of drugs and iii) using support vector machine classifier for inferring DDIs. We obtained 6036 DDIs from DrugBank database. Using the proposed approach, we inferred 589 drug pairs that are likely to not interact with each other; these drug pairs are used as representative data for the negative class in binary classification for DDI prediction. Moreover, we classify the predicted DDIs as Cytochrome P450 (CYP) enzyme-Dependent and CYP-Independent interactions invoking their locations on the Growing Self Organizing Map, due to the particular importance of these enzymes in clinically significant interaction effects. Further, we provide a case study on three predicted CYP-Dependent DDIs to evaluate the clinical relevance of this study. CONCLUSION: Our proposed approach showed an absolute improvement in F1-score of 14 and 38% in comparison to the method that randomly selects unlabeled data points as likely negatives, depending on the choice of similarity function. We inferred 5300 possible CYP-Dependent DDIs and 592 CYP-Independent DDIs with the highest posterior probabilities. Our discoveries can be used to improve clinical care as well as the research outcomes of drug development.

Sex differences in psychotomimetic-induced behaviours in rats.

Animal model studies using equal numbers of males and females are sparse in psychiatry research. Given the marked sex differences observed in psychiatric disorders, such as schizophrenia, using both males and females in research studies is an important requirement. Thus the aim of this study was to examine sex differences in psychotomimetic-induced behavioural deficits relevant to psychosis. We therefore compared the acute effect of amphetamine or phencyclidine on locomotor activity and prepulse inhibition in adult male and female Sprague-Dawley rats. The results of this study were that: (1) amphetamine-induced distance travelled was greater in female rats than in male rats, (2) phencyclidine-induced locomotor hyperactivity was similar in male and female rats; (3) there were no sex differences in amphetamine- or phencyclidine-induced disruption of prepulse inhibition; (4) male rats had an increased startle response after amphetamine. These findings suggest that sensitivity to amphetamine, but not phencyclidine, differs between male and female rats, and that this sex difference is selective to locomotor hyperactivity and startle, but not prepulse inhibition. This study used two widely-used, validated preclinical assays relevant to psychosis; the results of this study have implications for psychiatry research, particularly for disorders where marked sex differences in onset and symptomology are observed.