Publications

Abdel Shaheed, C, Maher, CG, Williams, KA & McLachlan, AJ 2017, 'Efficacy and tolerability of muscle relaxants for low back pain: Systematic review and meta‐analysis', European Journal of Pain, vol. 21, no. 2, pp. 228-237.
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AbstractMuscle relaxants are commonly prescribed for low back pain (LBP); however, there is limited evidence of their clinical efficacy and tolerability. This review evaluated the efficacy and tolerability of muscle relaxants in people with LBP. We searched online databases including Medline, EMBASE, CENTRAL and PsycINFO (inception to end October 2015) and performed citation tracking for eligible randomized controlled trials (RCTs). Two authors independently extracted data and assessed risk of bias of randomized controlled trials of muscle relaxants. Pain outcomes were converted to a common 0–100 scale. Data were pooled using a random effects model with strength of evidence assessed using GRADE. Fifteen trials (3362 participants) were evaluated in this review. A total of five trials (496 participants) provide high quality evidence that muscle relaxants provide clinically significant pain relief in the short term for acute LBP; MD −21.3, [−29.0, −13.5]. There was no information on long‐term outcomes. The median adverse event rate in clinical trials for muscle relaxants was similar to placebo 14.1% IQR (7.0–28.7%) and 16.0% (4.1–31.2%); p = 0.5, respectively. There is no evidence for the efficacy of benzodiazepines in LBP

Alhawassi, TM, Krass, I & Pont, LG 2017, 'Prevalence, management and control of hypertension in older adults on admission to hospital', Saudi Pharmaceutical Journal, vol. 25, no. 8, pp. 1201-1207.
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© 2017 The Authors Introduction The aim of this study was to explore the prevalence and management of hypertension among older adults on admission to hospital and to assess the choice of antihypertensive pharmacotherapy in light of relevant comorbid conditions using the national treatment guideline. Materials and methods A retrospective cross sectional study of 503 patients aged 65 years or older admitted to a large metropolitan teaching hospital in Sydney Australia was conducted. The main outcome measures were prevalence of hypertension, blood pressure (BP) control, antihypertensive medication use and the appropriateness of antihypertensive medications. Results Sixty-nine percent (n = 347) of the study population had a documented diagnosis of hypertension and of these, approximately one third were at target BP levels on admission to hospital. Some concerns regarding choice of antihypertensive noted with 51% of those with comorbid diabetes and 30% of those with comorbid heart failure receiving a potentially inappropriate antihypertensive agent. Conclusions Despite the use of antihypertensive pharmacotherapy, many older adults do not have optimal BP control and are not reaching target BP levels. New strategies to improve blood pressure control in older populations especially targeting women, those with a past history of myocardial infarction and those on multiple antihypertensive medications are needed.

Arali, B, Madhu, A, Gupta, G, K. Chellappan, D & Dua, K 2017, 'Anti-Psychotic Activity of Aqueous Root Extract of Hemidesmus indicus: A Time Bound Study in Rats', Recent Patents on Drug Delivery & Formulation, vol. 11, no. 1, pp. 36-41.
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Aims and Background: Psychosis is a neurological disorder, which is usually defined as the “loss of contact with reality.” As medicine ‘Hemidesmusindicus’ holds a reputed place in all systems of medicine in India. It is given in the form of infusion, fine particles, or syrup. It is also a component of several medicinal preparations. The present research work is pertaining to find out an anti-psychotic activity of an aqueous root extract of Hemidesmusindicus- a time bound study in rats. Methods: In the present study, the dried roots of Hemidesmusindicus were crushed to a coarse powder and extracted with water under reflux for 36 hours to obtain the aqueous extract of roots of Hemidesmusindicus (AERHI). The extract was reconstituted in 2% aqueous tragacanth just before use and administered orally at a dose 0f 100 mg/kg, 300 mg/kg and 500 mg/kg. In a single dose study, the parameters were assessed after oral administration of the single dose of the AERHI, whereas in a multiple dose study, the animals daily received the suitable oral dose of the AERHI for a period of 30 days. The parameters were assessed on the 15 and 30 day. The antipsychotic activity was screened using Apomorphine induced Stereotyped behavior in rats and Haloperidol induced catalepsy models were used. In Apomorphine induced Stereotyped behavior inhibition of the Stereotyped behavior was considered to be anti-psychotic activity and in Haloperidol induced catalepsy, we observed whether the AERHI potentate or attenuate the catalepsy in rats. Results: In this study, the extract of Hemidesmusindicus significantly inhibited the stereotyped behavior induced by apomorphine in rats and also potentiate the catalepsy induced by haloperidol, thereby showing its anti-psychotic activity. Conclusion: All these observations imply that Hemidesmusindicus extract possesses anti-psychotic activity in experimental animals. th th

AWASTHI, R, Madan, JR, Kamate, VK & Dua, K 2017, 'Improving the solubility of nevirapine using a hydrotropyand mixed hydrotropy based solid dispersion approach', Polymers in Medicine, vol. 47, no. 2, pp. 83-90.
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Nevirapine, an antiviral drug, is a potent reverse transcriptase inhibitor (NNRTI). It is used in combination with nucleoside analogues for treatment of HIV type-1 (HIV-1) infection and AIDS. Nevirapine is a BCS class II drug which shows dissolution rate limited absorption.The aim of the present research was to provide a fast dissolving solid dispersion of nevirapine.The solubility of nevirapine was initially determined individually in four hydrotropic agents - namely urea, lactose, citric acid and mannitol - at a concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. The highest solubility was obtained in the 40% citric acid solution. Then different combinations of 2 and 3 hydrotropic agents in different ratios were used to determine solubility, so that the total concentration of hydrotropic agents was always 40%.The highest solubility was obtained in a solution of lactose and citric acid at the optimum ratio of 15:25. This optimized combination was utilized in preparing solid dispersions by a common solvent technique using distilled water as a solvent. The solid dispersions were evaluated for XRD, DSC and FTIR to show no drug-hydrotrope interaction.It was concluded that the concept of mixed hydrotropic solid dispersion is a safe, novel and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs by dissolving the drug in a nonionized form. The enhancement in solubility of nevirapine using hydrotropy is a clear indication of its potential to be used in the future for other poorly water-soluble drugs in which low bioavailability is a major concern.

Beuscart, J, Pont, LG, Thevelin, S, Boland, B, Dalleur, O, Rutjes, AWS, Westbrook, JI & Spinewine, A 2017, 'A systematic review of the outcomes reported in trials of medication review in older patients: the need for a core outcome set', British Journal of Clinical Pharmacology, vol. 83, no. 5, pp. 942-952.
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AimMedication review has been advocated as one of the measures to tackle the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. This study aimed to assess outcome reporting in trials of medication review in older patients.MethodsRandomized controlled trials (RCTs), prospective studies and RCT protocols involving medication review performed in patients aged 65 years or older in any setting of care were identified from: (1) a recent systematic review; (2) RCT registries of ongoing studies; (3) the Cochrane library. The type, definition, and frequency of all outcomes reported were extracted independently by two researchers.ResultsForty‐seven RCTs or prospective published studies and 32 RCT protocols were identified. A total of 327 distinct outcomes were identified in the 47 published studies. Only one fifth (21%) of the studies evaluated the impact of medication reviews on adverse events such as drug reactions or drug‐related hospital admissions. Most of the outcomes were related to medication use (n = 114, 35%) and healthcare use (n = 74, 23%). Very few outcomes were patient‐related (n = 24, 7%). A total of 248 distinct outcomes were identified in the 32 RCT protocols. Overall, the number of outcomes and the number and type of health domains covered by the outcomes varied largely.ConclusionOutcome reporting from RCTs concerning medication review in older patients is heterogeneous. This review highlights the need for a standardized core outcome set for medication review in older patients, to improve outcome reporting and evidence synthesis.

Das, P, Gupta, G, Velu, V, Awasthi, R, Dua, K & Malipeddi, H 2017, 'Formation of struvite urinary stones and approaches towards the inhibition—A review', Biomedicine & Pharmacotherapy, vol. 96, pp. 361-370.
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Struvite is one of the most common urinary/kidney stones, composed of magnesium ammonium phosphate (MgNHPO4·H2O). They are also termed as infection stones as these are associated with urinary tract infections. Numerous studies have been carried out to examine the growth and inhibition of struvite stones.This review summarizes various reports on the factors responsible for inducing struvite stones in the kidney and gives a detailed account of studies on inhibition of growth of struvite crystals.The presence of urea-splitting bacteria such as Proteus mirabilis and alkaline pH plays a crucial role in struvite formation. In vitro inhibition of struvite stones by various chemical agents were examined mainly in artificial urine whereas inhibition by herbal extracts was studied in vitro by gel diffusion technique. Herbal extracts of curcumin, Boerhaavia diffusa Linn, Rotula aquatica and many other plants, as well as some chemicals like pyrophosphate, acetohydroxamic acid, disodium EDTA and trisodium citrate, were reported to successfully inhibit struvite formation.The present review recapitulates various factors affecting the growth of struvite urinary stones and the inhibitory role of certain chemicals and herbal extracts. Most of the tested plants are edible hence can be easily consumed without any adverse effects whereas the side effects of chemicals are unknown due to lack of toxicity studies. Thus, the use of herbal extracts might serve as an alternate and safe therapy for prevention of struvite stones.

Dua, K, D. Shukla, S & M. Hansbro, P 2017, 'Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties', Journal of Biological Methods, vol. 4, no. 3, pp. 1-1.
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Bronchoalveolar lavage (BAL) is a simple, yet informative tool in understanding the immunopathology of various lung diseases via quantifying various inflammatory cells, cytokines and growth factors. At present, this traditional method is often blended with several robust and sophisticated molecular and biological techniques sustaining the significance and longevity of this technique. Crucially, the existence of slightly distinct approaches and variables employed at different laboratories around the globe in performing BAL aspiration indeed demands an utmost need to optimize and develop an effective, cost-effective and a reproducible technique. This mini review will be of importance to the biological translational scientist, particularly respiratory researchers in understanding the fundamentals and approaches to apply and consider with BAL aspiration techniques. This will ensure generating a meaningful and clinically relevant data which in turn accelerate the development of new and effective therapeutic moieties for major respiratory conditions.

Dua, K, Hansbro, NG, Foster, PS & Hansbro, PM 2017, 'MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases', Drug Delivery and Translational Research, vol. 7, no. 1, pp. 168-178.
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© 2016, Controlled Release Society. The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.

Dua, K, Shukla, SD, Andreoli Pinto, TDJ & Hansbro, PM 2017, 'Nanotechnology: Advancing the translational respiratory research', INTERVENTIONAL MEDICINE AND APPLIED SCIENCE, vol. 9, no. 1, pp. 39-41.
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Dua, K, Shukla, SD, de Jesus Andreoli Pinto, T & Hansbro, PM 2017, 'Nanotechnology: Advancing the translational respiratory research', Interventional Medicine and Applied Science, vol. 9, no. 1, pp. 39-41.
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Considering the various limitations associated with the conventional dosage forms, nanotechnology is gaining increased attention in drug delivery particularly in respiratory medicine and research because of its advantages like targeting effects, improved pharmacotherapy, and patient compliance. This paper provides a quick snapshot about the recent trends and applications of nanotechnology to various translational and formulation scientists working on various respiratory diseases, which can help paving a new path in developing effective drug delivery system.

Dua, K, Shukla, SD, Tekade, RK & Hansbro, PM 2017, 'Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?', Drug Delivery and Translational Research, vol. 7, no. 1, pp. 179-187.
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© 2016, Controlled Release Society. Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.

Fong, J, Buckley, T, Cashin, A & Pont, L 2017, 'Nurse practitioner prescribing in Australia: A comprehensive literature review', Australian Critical Care, vol. 30, no. 5, pp. 252-259.
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In Australia, the nurse practitioner (NP) obtained prescriptive authority in some jurisdictions in 2001. One of the key aspects in which the scope of NPs differs from Registered Nurses (RNs) relates to the legal privilege to prescribe medications. Although NPs have had prescriptive authority in Australia since 2001, with access to the Commonwealth subsidy scheme (PBS) since 2010, little is known about NPs prescriptive patterns or outcomes of prescriptive practice.The aim of this scoping review was to examine the extent, range and nature of research conducted in relation to NP prescribing in the Australian health context as well as identify gaps in the existing literature. Whilst considerable research has been undertaken on medical prescribing, to date there is no published review of studies regarding NP prescribing in the Australian context.A structured search of the literature was undertaken using permutations of the following key words ’nurse practitioner prescribing Australia’, ’nurse practitioner and prescribing’, ’advanced practice nurse and prescribing’, ’nurse practitioner and Australia’. Databases where searched from January 2000 to January 2016. Databases searched include PsycInfo, Pubmed, CINAHL and Medline.There are a number of distinguishing features of NP prescribing practices in the Australian context. Little is known about the prescribing behaviours of critical care NPs in both the international and Australian context. Key themes identified were: barriers to prescribing, attitudes to NP prescribing, frequency of prescribing, types of medications prescribed, prescribing practice behaviours and confidence in prescribing.The impact of legislative changes on Australian NPs clinical practice and service delivery is still evolving. This review should create impetus for further research to determine the outcomes of NP prescribing on both patient and health service outcomes in the Australian healthcare context including critical care settings.

Gupta, G, Chellappan, DK, Agarwal, M, Ashwathanarayana, M, Nammi, S, Pabreja, K & Dua, K 2017, 'Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3)-Induced Memory Impairment in Rats', Central Nervous System Agents in Medicinal Chemistry, vol. 17, no. 3, pp. 196-200.
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BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels. RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels. CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.

Gupta, G, Chellappan, DK, Kikuchi, IS, Pinto, TDJA, Pabreja, K, Agrawal, M, Singh, Y, Tiwari, J & Dua, K 2017, 'Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of Moralbosteroid, a Steroidal Glycoside', Journal of Environmental Pathology, Toxicology and Oncology, vol. 36, no. 2, pp. 113-119.
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Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.

Hansbro, PM, Kim, RY, Starkey, MR, Donovan, C, Dua, K, Mayall, JR, Liu, G, Hansbro, NG, Simpson, JL, Wood, LG, Hirota, JA, Knight, DA, Foster, PS & Horvat, JC 2017, 'Mechanisms and treatments for severe, steroid‐resistant allergic airway disease and asthma', Immunological Reviews, vol. 278, no. 1, pp. 41-62.
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SummarySevere, steroid‐resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid‐resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid‐resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid‐resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid‐resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity‐or pollution‐associated asthma.

Hsu, AC-Y, Dua, K, Starkey, MR, Haw, T-J, Nair, PM, Nichol, K, Zammit, N, Grey, ST, Baines, KJ, Foster, PS, Hansbro, PM & Wark, PA 2017, 'MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD', JCI Insight, vol. 2, no. 7, pp. e90443-e90443.
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Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects. In pBECs from COPD patients, infections resulted in exaggerated inflammatory but deficient antiviral responses. A20 is an important negative regulator of NF-κB-mediated inflammatory but not antiviral responses, and A20 expression was reduced in COPD. IAV infection increased the expression of miR-125a or -b, which directly reduced the expression of A20 and mitochondrial antiviral signaling (MAVS), and caused exaggerated inflammation and impaired antiviral responses. These events were replicated in vivo in a mouse model of experimental COPD. Thus, miR-125a or -b and A20 may be targeted therapeutically to inhibit excessive inflammatory responses and enhance antiviral immunity in IAV infections and in COPD.

Kikuchi, IS, Cardoso Galante, RS, Dua, K, Malipeddi, VR, Awasthi, R, Ghisleni, DDM & de Jesus Andreoli Pinto, T 2017, 'Hydrogel Based Drug Delivery Systems: A Review with Special Emphasis on Challenges Associated with Decontamination of Hydrogels and Biomaterials', Current Drug Delivery, vol. 14, no. 7, pp. 917-925.
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© 2017 Bentham Science Publishers. Background: Many researches involving the development of new techniques and biomaterials to formulate a suitable drug delivery system and tissue engineering have been conducted. The majority of published literature from these researches emphasizes the production and materials characterization. The safety aspect of hydrogels and biomaterials is a major constraint in their biological applications. Objective: The present review article aimed to summarize various literatures that encompass the difficulties encountered with decontamination and sterilization methods in the preparations of biomaterials and especially hydrogels for biological applications. Method: We searched for original and review articles from various indexed journals reporting applications of hydrogels and biomaterials in drug delivery systems and the importance of decontamination process for hydrogel containing preparations based on various patents evidences. Results: Despite the vast literature available, limited information regarding the decontamination and sterilization processes related to hydrogels and biomaterials is reported. Sterilization processes to hydrogels are not yet fully explored. Researchers working on hydrogel based systems can consider decontamination of such biomaterial as an important tool to allow for commercialization within the chemical, herbal or pharmaceutical industries. Conclusion: Unfortunately, till date, limited papers are available which reported the challenges associated with decontamination methods to prepare hydrogels and biomaterials for biological applications. In conclusion, each case of biomaterial requires individual consideration to decontamination and/or sterilization. This must be submitted to a specific method, but more than one technique can be involved. Physicochemical and biological alterations must be avoided and evaluated by the appropriate assays method. Furthermore, it is also important to consider that e...

Lyell, D, Magrabi, F, Raban, MZ, Pont, LG, Baysari, MT, Day, RO & Coiera, E 2017, 'Automation bias in electronic prescribing', BMC Medical Informatics and Decision Making, vol. 17, no. 1, pp. 1-10.
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© 2017 The Author(s). Background: Clinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB. Methods: One hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured. Results: Compared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB. Conclusions: This study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS.

Madan, JR, Kamate, VJ, Awasthi, R & Dua, K 2017, 'Formulation, Characterization and In-vitro Evaluation of Fast Dissolv ing Tablets Containing Gliclazide Hydrotropic Solid Dispersions', Recent Patents on Drug Delivery & Formulation, vol. 11, no. 2, pp. 147-154.
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Low aqueous solubility is a major problem faced with new drug molecules. The purpose of this research was to provide a fast dissolving oral dosage form of Gliclazide (GLZ) using the concept of mixed hydrotropy. The recent patents on Adenosine (US20140107059A1), Growth hormone releasing factor peptide (EP0984788A1) and Paclitaxel (WO2002030466A2) helped in selecting the hydrotropes.Solubility of GLZ was determined individually in sodium salicylate, nicotinamide, lactose, sodium acetate, urea, trisodium citrate and sodium benzoate. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope amount, mixed hydrotropic agents were used.Highest solubility was obtained in 25:15 ratio of sodium salicylate and sodium benzoate. This optimized combination was utilized in the preparation of solid dispersions which were evaluated for Xray diffractometry, Differential Scanning Calorimetry (DSC) and Fourier-transform infrared to show no drug-hydrotropes interaction. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus.The batch G3 tablets showed 86% cumulative drug release within 14min with in vitro dispersion time of 33sec. It was concluded that the enhancement in solubility of GLZ is a clear indication of the potential of mixed hydrotropy which is a novel, safe and cost-effective technique to be employed for other poorly water-soluble drugs having low bioavailability.

Mahmood, MQ, Shukla, SD, Dua, K & Shastri, MD 2017, 'The Role of Epidermal Growth Factor Receptor in the Management of Gastrointestinal Carcinomas: Present Status and Future Perspectives', Current Pharmaceutical Design, vol. 23, no. 16, pp. 2314-2320.
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© 2017 Bentham Science Publishers. Background: The global burden of gastrointestinal cancers, including colorectal, stomach, and esophageal cancers is rising steadily. Several therapeutic approaches have been considered for the treatment of GI carcinomas. However, none showed to halt or cure the disease. There is a need to develop effective targeted molecular therapies; mainly to overcome the adverse effects of currently used treatment regimens, as well as, to benefit a large proportion of cancer patients who do not respond well to chemotherapeutics. Methods: Epidermal growth factor receptor (EGFR) is one of the promising targets for cancer therapy. Through a cascade of events, activation of EGFR plays an important role in the homeostasis and pathogenesis of various disorders, including carcinomas of the gastrointestinal (GI) tract, ranging from oesophagitis to complex colon carcinoma. Results: The GI carcinomas are associated with aberrant EGFR expression. In this review, emphasis was made on various EFGR-associated signalling pathways, their mechanisms and role in the formation of gastrointestinal lesions. Conclusion: The current EGFR-targeting therapeutics and an outline of various novel drug delivery systems that could potentially be employed for targeting EGFR during cancer treatment were discussed. This would help medical, pharmaceutical and other life science researchers in providing broad understanding of the work previously conducted in this field.

Malipeddi, VR, Awasthi, R, Ghisleni, DDM, de Souza Braga, M, Kikuchi, IS, de Jesus Andreoli Pinto, T & Dua, K 2017, 'Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system', Drug Delivery and Translational Research, vol. 7, no. 1, pp. 66-76.
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© 2016, Controlled Release Society. The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Panth, N, Manandhar, B & Paudel, KR 2017, 'Anticancer Activity ofPunica granatum(Pomegranate): A Review', Phytotherapy Research, vol. 31, no. 4, pp. 568-578.
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Copyright © 2017 John Wiley & Sons, Ltd. Cancer is a pathological condition where excessive and abnormal cell growth leads to widespread invasion within the body to affect various organ functions. It is known that chemotherapeutic agents are themselves possible candidate of cancer generation as they can kill normal cells. So, therapeutic approach for cancer treatment and prevention is weighed in terms of benefit to risk ratio. Nowadays, there is an immense interest for the search herbal formulation with cancer preventive effect because of the problems, generated with existing chemotherapeutic regimens. Research interest in fruits rich in polyphenols is increasing because of their anticancer potential. In this review, we highlight the potential health benefits of pomegranate (Punica granatum) fruit and the underlying mechanism of its inhibition of cancer progression. Pomegranate has demonstrated anti-proliferative, anti-metastatic and anti-invasive effects on various cancer cell line in vitro as well as in vivo animal model or human clinical trial. Although several clinical trials are in progress for identifying the pomegranate as a candidate for various cancer treatment. It is necessary to replicate and validate its therapeutic efficacy by multiple clinical studies in order to formulate pomegranate products as an integral part of the dietary and pharmacological intervention in anticancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Pont, LG 2017, 'Playing ball with the Red Sox: the 31^st International Conference on Phamacoepidemiology and Therapeutic Risk Management, Boston, USA', Journal of Pharmacy Practice and Research, vol. 47, no. 5, pp. 402-402.
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As a 2015 recipient of the Pfizer Pharmacy Grant, I attended the 31st International Conference on Phamacoepidemiology and Therapeutic Risk Management in Boston from August 21–26, 2015. The International Conference on Pharmacoepidemiology (ICPE) is the annual meeting of the International Society of Pharmacoepidemiology (ISPE) and alternates annually between North America and Europe. Approximately 1500 researchers, clinicians, regulators, policy makers and academics from around the world attended the conference. Prior to the main meeting, ISPE runs 2 days of pre‐conference educational courses in a number of specialty areas. I was involved in the Introduction to Drug Utilisation Research session, which introduced participants to the basic principles, methodologies, resources and use of drug utilisation research, including a session presented by the World Health Organization on their ATC/DDD (Anatomic Therapeutic Classification/Defined Daily Dose) methodology.1 I was also involved with colleagues from France and USA in a workshop on designing and conducting non‐database research where participants worked through a series of case studies to better understand the challenges of doing epidemiological research without large databases. Each day the conference ran multiple concurrent sessions, each with a different therapeutic or methodological focus. With my research interest, drug utilisation research among older persons, I was able to attend relevant and interesting sessions each day in the drug utilisation stream, which showcased international research. It was interesting to see that many of the issues we are struggling with around medication use among older persons are international challenges. One of the highlights of the meeting was the plenary session on ‘The eye of the beholder’, where adverse drug reactions were discussed from different perspectives, including those of a physician, the pharmaceutical industry, a lawyer, regulators and a patient. The patient ha...

Pont, LG, Morgan, TK, Williamson, M, Haaijer, FM & van Driel, ML 2017, 'Validity of prescribing indicators for assessing quality of antibiotic use in Australian general practice', International Journal of Pharmacy Practice, vol. 25, no. 1, pp. 66-74.
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© 2016 Royal Pharmaceutical Society Objectives: The aim of this study was to assess the validity of a set of European quality indicators for assessing antimicrobial prescribing in Australian General Practice. Methods: A modified UCLA/RAND appropriateness method was used to assess the validity of 30 antimicrobial prescribing indicators. An expert panel of 12 general practitioners scored the validity of each indicator for measuring quality in Australian general practice. Four quality domains were considered: monitoring antibiotic resistance, benefit to individual patients, value for money and value to policymakers. Panel members were also asked to comment on the relevance to the Australian context and proposed benchmarks for each indicator. Key findings: All panel members were in agreement regarding the validity of each indicator in each of the specified domains with exception of the indicator assessing the use of systemic antibiotics for pneumonia. The majority of the indicators and their associated benchmarks were considered valid for assessing quality in Australian General Practice, however, there were differences regarding the quality domain that each indicator was considered valid for. Monitoring quality considering individual patient benefit was the most problematic domain with respect to validity. Conclusions: This study demonstrates the validity of 30 European indicators for assessing quality of antimicrobial prescribing in general practice in a non-European setting and provides guidance regarding acceptable benchmarks for the indicators. With international concerns regarding misuse of antibiotics and global interest in prescribing quality, valid evidence-based antimicrobial prescribing indicators and associated benchmarks are an essential tool for assessing prescribing quality.

Sharma, S, Pathak, S, Gupta, G, Sharma, SK, Singh, L, Sharma, RK, Mishra, A & Dua, K 2017, 'Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet—Role of PPARγ and PPARα', Biomedicine & Pharmacotherapy, vol. 89, pp. 447-453.
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© 2017 Elsevier Masson SAS In India syzygium cumini (Myrtaceae) is commonly used traditional medicine to treat diabetes. The present study was undertaken to assess an investigation of antihyperglycemic and antidyslipidemic properties of aqueous extract of Syzigium Cumini (SC) in diabetic rats fed a high cholesterol diet. The aqueous extract of SC was screened for antihyperglycemic and antidyslipidemic activity by streptozotocin induced diabetes in rats. Animals were treated with 100, 200 and 400 mg/kg body weight of aqueous extract of SC. Metformin were used as reference antihyperglycemic drugs for comparison. Administration of aqueous extract of SC or metformin for 21 days resulted in a significant (P < 0.05) reduction in serum glucose, insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) compared with diabetic controls. Treatment with 100 mg/kg/day aqueous extract of SC did not result in a significant reduction in serum insulin levels, but 200 mg/kg/day and 400 mg/kg/day, aqueous extract of SC and metformin showed significant reductions 17.89%, 19.60% and 24.40%, respectively. Furthermore, administration of 100, 200 and 400 mg/kg/day, aqueous extract of SC and metformin resulted in significant decrease in insulin resistance of 19.20%, 41.59%, 51.55% and 68.68%, respectively. In high fat diet- streptozotocin (HFD – STZ) treated rats β-cells function (HOMA-B) were markedly reduced (5.8-fold), however observed a significant (P < 0.01) improvement of β-cell function with aqueous extract of SC (400 mg/kg/day) and metformin. The aqueous extract of SC seeds exhibits significant insulin-sensitizing, antidyslipidemic, antioxidant, anti-inflammatory and β-cell salvaging activity in HFD-STZ-induced type 2 diabetic rats via overexpression of PPARγ and PPARα activity, affirming its potential to be used in the prevention and treatment of type 2 diabetes mellitus (T2DM). Further isolation and characterization of active components in SC seed extra...

Singh, Y, Gupta, G, Shrivastava, B, Dahiya, R, Tiwari, J, Ashwathanarayana, M, Sharma, RK, Agrawal, M, Mishra, A & Dua, K 2017, 'Calcitonin gene‐related peptide (CGRP): A novel target for Alzheimer's disease', CNS Neuroscience & Therapeutics, vol. 23, no. 6, pp. 457-461.
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SummaryAlzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid‐β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene‐related peptide (CGRP) is a thirty‐seven‐amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor‐stimulating peptide. It is a proof for a CGRP receptor within nucleus accumbens of brain that is different from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high‐affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases activated cAMP‐dependent pkA and PI3 kinase, resulting in N‐terminal fragments that are shown to exert complex inhibitory as well facilitator actions on nAChRs. Fragments such as

Soni, N, Tekade, M, Kesharwani, P, Bhattacharya, P, Maheshwari, R, Dua, K, Hansbro, PM & Tekade, RK 2017, 'Recent Advances in Oncological Submissions of Dendrimer', Current Pharmaceutical Design, vol. 23, no. 21, pp. 3084-3098.
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© 2017 Bentham Science Publishers. Background: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients. Methods: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body. Results: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation. Conclusion: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.

Taxis, K, Kochen, S, Wouters, H, Boersma, F, Jan Gerard, M, Mulder, H, Pavlovic, J, Stevens, G, McLachlan, A & Pont, LG 2017, 'Cross-national comparison of medication use in Australian and Dutch nursing homes', Age and Ageing, vol. 46, no. 2, pp. 320-323.
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© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. Background: cross-national comparisons can be used to explore therapeutic areas and identify potential medication issues. Methods: we used cross-sectional pharmacy supply data to explore medication use for nursing home residents in Australia (AU n = 26 homes, 1,560 residents) and the Netherlands (NL n = 6 homes, 2,037 residents). Binary logistic regression analysis was used to calculate the sex and aged adjusted odds ratios (OR) and associated 95% confidence intervals with a flexible Bonferroni-Holm procedure used to adjust for multiple hypothesis testing. Results: total use of antipsychotics (AU: 37.7%, NL: 40.3%; OR 0.91 (0.79-1.04, P = 0.16) and antibacterials (66.8% AU, 62.4% NL, OR 1.08 (0.93-1.24, P = 0.31) was similar, but choice of individual agents differed between the two countries. Differences were observed in the use of antithrombotics (46.7% AU, 64.7% NL, OR 0.48 (0.42-0.56, P > 0.01), ophthalmologicals (44.3% AU, 22.1% NL, OR 2.80 (2.42-3.24, P < 0.001), laxatives (77.1% AU, 65.8% NL, OR 1.65 (1.41-1.92, P < 0.001). Conclusion: while the general prevalence of medication use in nursing home residents was similar across the two countries, distinct differences existed in the choice of agent among therapeutic groups. Comparing use between countries identified a number of potential medication related problem areas that need further exploration.

Velu, V, Das, M, Raj N, AN, Dua, K & Malipeddi, H 2017, 'Evaluation of in vitro and in vivo anti-urolithiatic activity of silver nanoparticles containing aqueous leaf extract of Tragia involucrata', Drug Delivery and Translational Research, vol. 7, no. 3, pp. 439-449.
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The present investigation is focused on exploring the anti-urolithiatic potential of aqueous leaf extract of Tragia involucrata (TIA) and its silver nanoparticles (AgNPs) and to quantify the total phenol, flavonoid, terpenoid and sterol contents present in TIA. Quantification results suggested TIA to be a rich source of phenol, flavonoid and terpenoid and less of sterol content. The AgNPs were synthesized by a simple green method using aqueous extract of T. involucrata. The formation of AgNPs was confirmed through UV spectroscopy, particle size analysis, zeta potential, X-ray diffraction and transmission electron microscopy. The in vitro struvite growth inhibitory activity of the extract was performed using a single gel diffusion method. Samples incorporated with higher concentration of 2% TIA and AgNPs (200 μg mL-1) exhibited potent crystal growth inhibitory activity which was further supported by the dissolution of crystals in gel medium. Calcium oxalate stone formation was induced in rats by the oral administration of ethylene glycol in water. Stone formation was assessed by increase in the levels of calcium and phosphorous in the urine and accumulation of nitrogenous substances like urea, creatinine in renal tissues and blood. Prophylactic treatment with TIA and AgNPs showed significant anti-urolithiatic activity with normalization of the mineral contents of the urine and serum samples. Histopathological analysis of the kidney of TIA- and AgNP-treated animals showed no CaOx deposits and a normal architecture of the kidney cells. We conclude that aqueous extract of T. involucrata and its AgNPs has potential for the treatment of patients with recurrent stones.

Werth, BL, Williams, KA & Pont, LG 2017, 'Laxative Use and Self-Reported Constipation in a Community-Dwelling Elderly Population', Gastroenterology Nursing, vol. 40, no. 2, pp. 134-141.
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The objectives of this study were to (1) determine the prevalence of laxative use and self-reported constipation and (2) identify risk factors associated with constipation in a community-dwelling elderly population. A retrospective cross-sectional survey using data from the Australian Longitudinal Study of Ageing was used to explore laxative use and constipation in a cohort of community-dwelling older persons. The prevalence of laxative use was 15% and the prevalence of self-reported constipation was 21%. Females were more likely to report constipation and use laxatives. Of those using laxatives, men were more likely to have their laxatives prescribed by a doctor whereas women were more likely to self-medicate. Poor self-rated health and a higher need for assistance with activities of daily living were identified as risk factors for constipation. Constipation is a common condition affecting the community-dwelling elderly. There is a need to optimize the management of constipation and use of laxatives in such populations.

Benson, H, Lucas, C, Benrimoj, S & Williams, KA 1970, 'Integrating Pharmacists in General Practice: Drug Related Problems in the Patient Centred Medical Home', Pharmaceutical Society of Australia National Conference (PSA17), Sydney.

Caughey, GE, Taxis, K, Pont, LG, Zongo, A & Wettermark, B 1970, 'Evidence Generation in Multimorbidity: A New Frontier in Drug Utilization', PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, WILEY, pp. 253-254.

Pont, LG, Raban, M, Georgiou, A & Westbrook, J 1970, 'Medicine Use Profiles in Residential Aged Care: Can They Inform Policy and Guide Practice?', PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, WILEY, pp. 137-137.

Pont, LG, Raban, MZ, Siette, J, Mitchell, R, Georgiou, A & Westbrook, J 1970, 'Antipsychotics Are Forever? De-Prescribing of Antipsychotics in Residential Aged Care', PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, WILEY, pp. 329-330.

Dua, K, Hansbro, NG & Hansbro, PM 2017, 'Steroid resistance and concomitant respiratory infections: A challenging battle in pulmonary clinic.', NCBI, pp. 981-985.
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Gupta, G, Dahiya, R, Dua, K, Chellappan, DK, Tiwari, J, Narayan Sharma, G, Kumar Singh, S, Mishra, A, Kumar Sharma, R & Agrawal, M 2017, 'Anticonvulsant effect of liraglutide, GLP-1 agonist by averting a change in GABA and brain glutathione level on picrotoxin-induced seizures.', EXCLI JOURNAL MANAGING OFFICE, pp. 752-754.
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Starkey, MR, Dua, K, Hsu, AC, Nair, PM, Haw, TJ, Nguyen, DH, Kim, RY, Horvat, JC, Godfrey, DI, McKenzie, A, Lukacs, NW, Wark, PAB & Hansbro, PM 2017, 'Interleukin-13 Predisposes To More Severe Influenza Infection In Mice And Human Epithelial Cells By Suppressing Interferon Responses And Activating The Microrna-21/pi3k Signaling Pathway', AMER THORACIC SOC.

Taxis, K, Kochen, S, Wouters, H, Boersma, F, Jan Gerard, M, Mulder, H, Pavlovic, J, Stevens, G, Andrew, M & Pont, LG 2017, 'Cross-national comparison of medication use in Australian and Dutch nursing homes', Oxford University Press (OUP), p. 319.
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The author would like to apologise for an error in the originally published paper. One of the authors' names appeared incorrectly in the originally published paper. 'McLachlan Andrew' has been corrected to 'Andrew McLachlan'.

Tiwari, J, Gupta, G, Dahiya, R, Pabreja, K, Kumar Sharma, R, Mishra, A & Dua, K 2017, 'Recent update on biological activities and pharmacological actions of liraglutide.', pp. 742-747.
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Tsingos-Lucas, C, Williams, KA, Smith, L, Lonie, JM & Woulfe, J 2017, 'Development and Utilisation of a Structured ePortfolio to Support Attainment of Pharmacy Practice Competencies'.