Syed Tabish R. Zaidi

Impact of pharmacist recommendations on the cost of drug therapy in ICU patients at a Malaysian hospital

Objectives: To analyse clinical pharmacists interventions in the ICU of the Penang General Hospital (Penang, Malaysia) and to assess the pharmaco-economic impact of these interventions.Methods: A clinical pharmacist reviewed drug prescriptions during one month. Drug-related problems were documented on a preprepared form including a suggestion for a change in prescribing. Such recommendations were submitted to the nursing/medical staff. Acceptance of the recommendation was entirely at the discretion of the medical staff. All recommendations were analysed with respect to potential pharmaco-economic impact: cost savings, cost avoidance or cost addition.Results: The ICU pharmacist made 57 recommendations, of which the medical staff rejected only 5%. The majority of detected drug-related problems referred to unnecessary drug therapy (37%). Recommendations resulted in net cost savings of RM 15,227 (USD 4,007). This corresponded with RM 634 per patient intervened by the pharmacist. Conclusion: Pharmacists interventions in the ICU of a Malaysian hospital resulted in significant cost savings in terms of drug expenses and can therefore be suggested as a routine practice in our hospital.

Nonadherence to Medication Therapy in Haemodialysis Patients: A Systematic Review

Background End-stage kidney disease (ESKD) patients are often prescribed multiple medications. Together with a demanding weekly schedule of dialysis sessions, increased number of medicines and associated regimen complexity pre-dispose them at high risk of medication nonadherence. This review summarizes existing literature on nonadherence and identifies factors associated with nonadherence to medication therapy in patients undergoing haemodialysis. Methods A comprehensive search of PubMed, Embase, CINAHL, PsycInfo, and Cochrane Database of Systematic Reviews covering the period from 1970 through November 2014 was performed following a predefined inclusion and exclusion criteria. Reference lists from relevant materials were reviewed. Data on study characteristics, measures of nonadherence, prevalence rates and factors associated with nonadherence were collected. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was followed in conducting this systematic review. Results Of 920 relevant publications, 44 were included. The prevalence of medication nonadherence varied from 12.5% to 98.6%, with widespread heterogeneity in measures and definitions employed. Most common patient-related factors significantly associated with nonadherence were younger age, non-Caucasian ethnicity, illness interfering family life, being a smoker, and living single and being divorced or widowed. Similarly, disease-related factors include longevity of haemodialysis, recurrent hospitalization, depressive symptoms and having concomitant illness like diabetes and hypertension. Medication-related factors such as daily tablet count, total pill burden, number of phosphate binders prescribed and complexity of medication regimen were also associated with poor adherence. Conclusions A number of patient-, disease-, and medication-related factors are associated with medication nonadherence in haemodialysis patients. Clinicians should be aware of such factors so that adherence to medications can be optimised in haemodialysis patients. Future research should be directed towards well-designed prospective longitudinal studies developing standard definitions and validating available measurement tools, while focusing on the role of additional factors such as psychosocial and behavioural factors in predicting nonadherence to medications.

Combating sale of counterfeit and falsified medicines online: a losing battle

The rapid growth of technology has transformed many brick-and-mortar businesses into online businesses, and medicines are now being sold over the internet. Influenced by the notions that online purchases are economical and do not require a prescription, the general public are keen to purchase medicine online through websites, social media and mobile apps. Online medicine purchase is presumed to be convenient and confidential, free from embarrassment of sharing personal and sensitive health information to a healthcare professional. Public in United States, Europe, Australia is generally aware that internet sales form part of the official medicines distribution channels, often a valid prescription is required for controlled medicine. However, unlicensed, substandard and falsified medicines with various dubious medical claims are advertised and sold illegally in many rogue online pharmacies (Jack, 2016). These include medications for weight loss, hair growth, and treatment of erectile dysfunction. Such medicines are termed as substandard, spurious, falsely labeled, falsified and counterfeit medical products by the World Health Organisation (WHO). Similarly, the European Commission defines such products as falsified medicines or fake medicines that pass themselves off as real, authorized medicines (European Commission, 2016). These medicines may contain substandard active ingredients, which are low quality and/or an incorrect amount, either too high or too low, and have not been properly evaluated by authorities in terms of quality, safety, and efficacy. It must be noted that falsified medicines are often confused with counterfeit medicines. According to European Commission, counterfeit medicines refers to medicines that do not comply with European Union law on intellectual and industrial property rights, for example, unregistered medicines sourced from parallel import (European Medicines Agency). In this article, the illegal sales of both counterfeit and falsified medicines (CFMs) are discussed. In 2012, the WHO estimated the CFMs industry to be worth USD 431 billion a year, but further estimates has not been reported in the recent years due to the fast growing, widespread practice of this industry, making it impractical to estimate on a global scale (Garrett, 2012). Authorities are finding it difficult to curb CFMs due to the lack of governance over the internet. Furthermore, fragmented cybercrime legislation leads to large substantive and procedural lacunae in law, rendering law enforcement efforts useless.

Non-Anticoagulant Fractions of Enoxaparin Suppress Inflammatory Cytokine Release from Peripheral Blood Mononuclear Cells of Allergic Asthmatic Individuals

Background Enoxaparin, a low-molecular-weight heparin, is known to possess anti-inflammatory properties. However, its clinical exploitation as an anti-inflammatory agent is hampered by its anticoagulant effect and the associated risk of bleeding. Objective The aim of the current study was to examine the ability of non-anticoagulant fractions of enoxaparin to inhibit the release of key inflammatory cytokines in primed peripheral blood mononuclear cells derived from allergic mild asthmatics. Methods Peripheral blood mononuclear cells from allergic asthmatics were activated with phytohaemag glutinin (PHA), concanavalin-A (ConA) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of enoxaparin fractions before cytokine levels were quantified using specific cytokine bead arrays. Together with nuclear magnetic resonance analysis,time-dependent and target-specific effects of enoxaparin fractions were used to elucidate structural determinants for their anti-inflammatory effect and gain mechanistic insights into their anti-inflammatory activity. Results Two non-anticoagulant fractions of enoxaparin were identified that significantly inhibited T-cell activation. A disaccharide fraction of enoxaparin inhibited the release of IL-4, IL-5, IL-13 and TNF-α by more than 57% while a tetrasaccharide fraction was found to inhibit the release of tested cytokines by more than 68%. Our data suggest that the observed response is likely to be due to an interaction of 6-O-sulfated tetrasaccharide with cellular receptor(s). Conclusion and Clinical Relevance The two identified anti-inflammatory fractions lacked anticoagulant activity and are therefore not associated with risk of bleeding. The findings highlight the potential therapeutic use of enoxaparin-derived fractions, in particular tetrasaccharide, in patients with chronic inflammatory disorders.

Opposing Effects of Low Molecular Weight Heparins on the Release of Inflammatory Cytokines from Peripheral Blood Mononuclear Cells of Asthmatics

Background T-cell-mediated inflammatory cytokines, such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF-α), play an important role in the initiation and progression of inflammatory airways diseases. Low-molecular-weight heparins (LMWHs), widely used anticoagulants, possess anti-inflammatory properties making them potential treatment options for inflammatory diseases, including asthma. In the current study, we investigated the modulating effects of two LMWHs (enoxaparin and dalteparin) on the release of cytokines from stimulated peripheral blood mononuclear cells (PBMCs) of asthmatic subjects to identify the specific components responsible for the effects. Methods PBMCs from asthmatic subjects (consist of ~75% of T-cells) were isolated from blood taken from ten asthmatic subjects. The PBMCs were pre-treated in the presence or absence of different concentrations of LMWHs, and were then stimulated by phytohaemagglutinin for the release of IL-4, IL-5, IL-13 and TNF-α. LMWHs were completely or selectively desulfated and their anticoagulant effect, as well as the ability to modulate cytokine release, was determined. LMWHs were chromatographically fractionated and each fraction was tested for molecular weight determination along with an assessment of anticoagulant potency and effect on cytokine release. Results Enoxaparin inhibited cytokine release by more than 48%, whereas dalteparin increased their release by more than 25%. The observed anti-inflammatory effects of enoxaparin were independent of their anticoagulant activities. Smaller fractions, in particular dp4 (four saccharide units), were responsible for the inhibitory effect of enoxaparin. Whereas, the larger fractions, in particular dp22 (twenty two saccharide units), were associated with the stimulatory effect of dalteparin. Conclusion Enoxaparin and dalteparin demonstrated opposing effects on inflammatory markers. These observed effects could be due to the presence of structurally different components in the two LMWHs arising from different methods of depolymerisation. This study provides a platform for further studies investigating the usefulness of enoxaparin in various inflammatory diseases.

Perceptions and practices of community pharmacists towards antimicrobial stewardship in the state of Selangor, Malaysia

Background Increasing antimicrobial resistance is one of the pressing concerns globally. Injudicious use of antibiotics is one of the modifiable factors responsible for antimicrobial resistance. Given the widespread use of antimicrobials in community settings, pharmacists have an important role in ensuring appropriate use of antibiotics. The objective of this study was to assess the perception and self-reported practices of community pharmacists towards antimicrobial stewardship. Methods A cross-sectional study was conducted among community pharmacists between March–April, 2015, using a self-administered, pre-tested questionnaire in the State of Selangor, Malaysia. A simple random sampling approach was used to select pharmacy sites. Descriptive and inferential statistical methods were used to analyse the data. Results A total of 188 pharmacists responded to the survey, giving a response rate of 83.5%. The majority of participants (n = 182, 96.8%) believed that antimicrobial stewardship program helps healthcare professionals to improve the quality of patient care. However, more than half of pharmacists were neutral in their opinion about the incorporation of antimicrobial stewardship programs in community pharmacies (n = 102, 54.2%). Though collaboration was often done by pharmacists with other health professionals over the use of antibiotics (n = 104, 55.3%), a significant proportion of participants (n = 102, 54.2%) rarely/occasionally participate in antimicrobial awareness campaigns. Pharmacists having postgraduate qualification were more likely to held positive perceptions of, and were engaged in, antimicrobial stewardship than their non-postgraduate counterpart (p<0.05). Similarly, more experienced pharmacists (> 10 years) held positive perceptions towards antimicrobial stewardship (p<0.05). Conclusion The study highlighted some gaps in the perception and practices of community pharmacist towards antimicrobial stewardship. Development of customized interventions would be critical to bridging these gaps and improve their perception and practices towards antimicrobial stewardship.

Medication Regimen Complexity and Adherence in Haemodialysis Patients: An Exploratory Study

Background: The impact of medication regimen complexity on adherence in hemodialysis patients is unknown. We investigated regimen complexity, perceived burden of medicines (PBM) and health-related quality of life (HR-QoL) as potential predictors of adherence. Methods: Adult (≥18 years) hemodialysis patients were included. Data on medication regimen complexity index (MRCI), self-reported and objective adherence, comorbidity index, PBM and HR-QoL were obtained using established measures. Sociodemographic and clinical characteristics were collected during interviews and by reviewing medical records. Predictors of adherence were determined using logistic regression. Results: Fifty-three out of 70 hemodialysis patients participated (response rate 75%; male 58.5%; age 67.9 ± 11.5 years). The mean MRCI, HR-QoL and PBM scores were 27.0 ± 10.9, 0.70 ± 0.13 and 1.7 ± 0.6, respectively. Based on self-reports, 43.4% (n = 23) were adherent, whereas for a subset of patients analyzed using objective measure (n = 33), much lower adherence rate was observed (27.3%, n = 9). The self-reported and objective measures were significantly correlated (r = 0.43, p = 0.01). Older age was the only significant predictor of self-reported adherence (OR 1.05; 95% CI 1.00-1.11) whereas older age (OR 1.10; 95% CI 1.00-1.21), higher comorbidity (OR 1.58; 95% CI 1.03-2.42) and MRCI (OR 1.14; 95% CI 1.02-1.27) were independent predictors of objective adherence. Conclusions: The findings of this exploratory study suggest that older patients with high comorbidities and highly complex regimen are more likely to be adherent based on an objective measure. Future research is needed using objective measures of adherence suitable for all patients and reflecting all medications.

Factors influencing ceftriaxone use in community-acquired pneumonia: Emergency doctors’ perspectives

To explore the perceptions of ED doctors regarding the use of ceftriaxone in patients with community‐acquired pneumonia (CAP).

Efficacy and safety of low‐dose colistin in the treatment for infections caused by multidrug‐resistant gram‐negative bacteria

Infections due to multidrug‐resistant gram‐negative bacteria (MDR‐GNB) are a significant burden to the healthcare system globally. Colistin is the drug of choice for MDR‐GNB and recent studies recommend high doses. This study investigated the safety of low‐dose colistin and the relationship of minimum inhibitory concentration (MIC) of colistin with bacterial cure in the treatment for MDR‐GNB infections.

The Crux of the Medicine Prices' Controversy in Pakistan

Drugs are regulated in Pakistan under the Drug Act 1976 and DRAP Act, 2012, under which the sales, storage, and distribution of drugs are regulated at provincial level while the manufacturing (licensing), registration, pricing, import, export, and monitoring of controlled drugs comes under the domain of federal government. The Drug Regulatory Authority of Pakistan (DRAP) established under the DRAP Act 2012 works under the federal government to regulate the aforementioned matters including fixation of prices. Prices are fixed by the Federal government under Section 12 of Drugs Act, 1976 after a recommendation of the Drug Pricing Committee (DPC) constituted the Statutory Regulatory Orders (SRO) on 6th August 2013 under the Cost and Pricing Division, DRAP. DPC is comprised of representatives from provincial health departments, Ministry of Finance and consumer bodies along with stakeholders as observers to proceedings of committee. In retrospective, the Pakistani government, particularly Drug Regulatory Authority of Pakistan (DRAP) in collaboration with provincial health departments are responsible for regulating the medicine prices and has taken various regulatory measures to address the issue of medicines accessibility, particularly on the medicines affordability and availability. Since 2001, there is a moratorium on price increase on 821 and 108 medicines through statutory regulatory orders SRO-100, SRO-328, respectively, before the establishment of DRAP. There are media reports that between June and August 2016, DRAP has approved price increases for four times but pharmaceutical companies were reported to have increased prices for at least five times (Chaudhry, 2016) but these reports are misleading. During the price moratorium, drug prices have not been revised despite of multifactorial burdens including increase in dollar exchange rate, fuel prices, inflation, material costs. Only with the exceptional cases of failure of a pharmaceutical manufacturer to continue manufacturing at the fixed price and accessibility of that drug was not ensured for general public. Moreover, some pharmaceutical companies increased prices of their medicines and were able to get stay orders from a provincial High Court to keep their price increased until the matter was resolved. DRAPs statutory power to regulate medicine prices were heavily opposed by the pharmaceutical industries who struggle to optimize their revenues due to limited wholesale mark-ups, ranging 2% (Cameron et al., 2009) to 10% (Mendis et al., 2007). It was getting practically non-viable for many companies including the multinationals to market their products in the same price as approved in 2001. These factors also led to stock-outs of essential medicine in healthcare institutions, especially public-funded hospitals. As a solution, to ensure the sustainability of local pharmaceutical industries and the accessibility of medicines, the first ever comprehensive Drug Pricing Policy 2015 was introduced (Drug Regulatory Authority of Pakistan, 2015). This new policy has laid down a transparent mechanism for fixation and price adjustment with an objective to help increasing availability of drugs at rational prices and discourage hoarding. Moreover, DRAP has also devised a monitoring mechanism with the coordination of the provincial health authorities working under the Provincial Quality Control Board to ensure that drugs are not sold in the market at prices higher than the approved range. According to this policy, prices of new drugs shall be fixed on the basis of average prices in India and Bangladesh and if new drug is not available in these countries price shall be fixed at the lowest level of the developing countries which regulate drugs prices or wholesale prices in UK, Australia, New Zealand. Moreover, a new concept of price reduction up to 30% on originator brands has been introduced with three staggered annual decrements. Drug Pricing Policy 2015 links the annual increase in medicine prices with the Consumer Price Index (CPI) as announced by Pakistan Bureau of Statistics, Government of Pakistan, with a maximum cap of 4% for scheduled drugs and 6% for non-scheduled drugs. For 2016, the proposed price increase in scheduled drugs and non-scheduled drugs was merely 1.43% and 2.00% respectively, based on CPI. It must be noted that the price hike is in fact unlawful as it had not been approved by Pakistani Federal Government.