A D-optimal designed population pharmacokinetic study of itraconazole capsules and solution in adults with cystic fibrosis

Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data.

Type 2 diabetes:assessing the relative risks and benefits of glucose-lowering medications

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications. © 2010 Elsevier Inc. All rights reserved.

The limits of open innovation:openness and (quasi-)markets in the organization of innovation

Recent studies have stressed the importance of ‘open innovation’ as a means of enhancing innovation performance. The essence of the open innovation model is to take advantage of external as well as internal knowledge sources in developing and commercialising innovation, so avoiding an excessively narrow internal focus in a key area of corporate activity. Although the external aspect of open innovation is often stressed, another key aspect involves maximising the flow of ideas and knowledge from different sources within the firm, for example through knowledge sharing via the use of cross-functional teams. A fully open innovation approach would therefore combine both aspects i.e. cross-functional teams with boundary-spanning knowledge linkages. This suggests that there should be complementarities between the use cross-functional teams with boundary-spanning knowledge linkages i.e. the returns to implementing open innovation in one innovation activity is should be greater if open innovation is already in place in another innovation activity. However, our findings – based on a large sample of UK and German manufacturing plants – do not support this view. Our results suggest that in practice the benefits envisaged in the open innovation model are not generally achievable by the majority of plants, and that instead the adoption of open innovation across the whole innovation process is likely to reduce innovation outputs. Our results provide some guidance on the type of activities where the adoption of a market-based governance structure such as open innovation may be most valuable. This is likely to be in innovation activities where search is deterministic, activities are separable, and where the required level of knowledge sharing is correspondingly moderate – in other words those activities which are more routinized. For this type of activity market-based governance mechanisms (i.e. open innovation) may well be more efficient than hierarchical governance structures. For other innovation activities where outcomes are more uncertain and unpredictable and the risks of knowledge exchange hazards are greater, quasi-market based governance structures such as open innovation are likely to be subject to rapidly diminishing returns in terms of innovation outputs.

A sustainable supply chain study of the Indian bioenergy sector

In India, more than one third of the population do not currently have access to modern energy services. Biomass to energy, known as bioenergy, has immense potential for addressing India’s energy poverty. Small scale decentralised bioenergy systems require low investment compared to other renewable technologies and have environmental and social benefits over fossil fuels. Though they have historically been promoted in India through favourable policies, many studies argue that the sector’s potential is underutilised due to sustainable supply chain barriers. Moreover, a significant research gap exists. This research addresses the gap by analysing the potential sustainable supply chain risks of decentralised small scale bioenergy projects. This was achieved through four research objectives, using various research methods along with multiple data collection techniques. Firstly, a conceptual framework was developed to identify and analyse these risks. The framework is founded on existing literature and gathered inputs from practitioners and experts. Following this, sustainability and supply chain issues within the sector were explored. Sustainability issues were collated into 27 objectives, and supply chain issues were categorised according to related processes. Finally, the framework was validated against an actual bioenergy development in Jodhpur, India. Applying the framework to the action research project had some significant impacts upon the project’s design. These include the development of water conservation arrangements, the insertion of auxiliary arrangements, measures to increase upstream supply chain resilience, and the development of a first aid action plan. More widely, the developed framework and identified issues will help practitioners to take necessary precautionary measures and address them quickly and cost effectively. The framework contributes to the bioenergy decision support system literature and the sustainable supply chain management field by incorporating risk analysis and introducing the concept of global and organisational sustainability in supply chains. The sustainability issues identified contribute to existing knowledge through the exploration of a small scale and developing country context. The analysis gives new insights into potential risks affecting the whole bioenergy supply chain.

Combining an enterprise resource planning system and informality:a study of efficiency and flexibility complmentarity [sic]

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT One of the current research trends in Enterprise Resource Planning (ERP) involves examining the critical factors for its successful implementation. However, such research is limited to system implementation, not focusing on the flexibility of ERP to respond to changes in business. Therefore, this study explores a combination system, made up of an ERP and informality, intended to provide organisations with efficient and flexible performance simultaneously. In addition, this research analyses the benefits and challenges of using the system. The research was based on socio-technical system (STS) theory which contains two dimensions: 1) a technical dimension which evaluates the performance of the system; and 2) a social dimension which examines the impact of the system on an organisation. A mixed method approach has been followed in this research. The qualitative part aims to understand the constraints of using a single ERP system, and to define a new system corresponding to these problems. To achieve this goal, four Chinese companies operating in different industries were studied, all of which faced challenges in using an ERP system due to complexity and uncertainty in their business environments. The quantitative part contains a discrete-event simulation study that is intended to examine the impact of operational performance when a company implements the hybrid system in a real-life situation. Moreover, this research conducts a further qualitative case study, the better to understand the influence of the system in an organisation. The empirical aspect of the study reveals that an ERP with pre-determined business activities cannot react promptly to unanticipated changes in a business. Incorporating informality into an ERP can react to different situations by using different procedures that are based on the practical knowledge of frontline employees. Furthermore, the simulation study shows that the combination system can achieve a balance between efficiency and flexibility. Unlike existing research, which emphasises a continuous improvement in the IT functions of an enterprise system, this research contributes to providing a definition of a new system in theory, which has mixed performance and contains both the formal practices embedded in an ERP and informal activities based on human knowledge. It supports both cost-efficiency in executing business transactions and flexibility in coping with business uncertainty.This research also indicates risks of using the system, such as using an ERP with limited functions; a high cost for performing informally; and a low system acceptance, owing to a shift in organisational culture. With respect to practical contribution, this research suggests that companies can choose the most suitable enterprise system approach in accordance with their operational strategies. The combination system can be implemented in a company that needs to operate a medium amount of volume and variety. By contrast, the traditional ERP system is better suited in a company that operates a high-level volume market, while an informal system is more suitable for a firm with a requirement for a high level of variety.

The devil is in the detail:tobacco industry political influence in the Dutch implementation of the 2001 EU Tobacco Products Directive

Introduction - The Dutch implementation of the black border provision in the 2001 European Union Tobacco Products Directive (TPD) is studied to examine the implications of tobacco industry involvement in the implementation phase of the policy process. Methods - A qualitative analysis was conducted of Dutch government documents obtained through Freedom of Information Act requests, triangulated with in-depth interviews with key informants and secondary data sources (publicly available government documents, scientific literature, and news articles). Results - Tobacco manufacturers’ associations were given the opportunity to set implementation specifications via a fast-track deal with the government. The offer of early implementation of the labelling section of the TPD was used as political leverage by the industry, and underpinned by threats of litigation and arguments highlighting the risks of additional public costs and the benefits to the government of expediency and speed. Ultimately, the government agreed to the industry's interpretation, against the advice of the European Commission. Conclusions - The findings highlight the policy risks associated with corporate actors’ ability to use interactions over technical product specifications to influence the implementation of health policy and illustrate the difficulties in limiting industry interference in accordance with Article 5.3 of the Framework Convention on Tobacco Control (FCTC). The implementation phase is particularly vulnerable to industry influence, where negotiation with industry actors may be unavoidable and the practical implications of relatively technical considerations are not always apparent to policymakers. During the implementation of the new TPD 2014/40/EU, government officials are advised to take a proactive role in stipulating technical specifications.

Understanding the risk of hypoglycaemia in older individuals with diabetes

Introduction: Although older individuals are more prone to hypoglycaemia, it is not known if they have sufficient understanding of the risks of hypoglycaemia or the factors that predispose to it. We evaluated the effectiveness of hypoglycaemia education and examined the factors that increased susceptibility to hypoglycaemia among older people with diabetes. Methods: Forty-five patients (male/female) aged >65 years and known to have diabetes were identified through outpatient clinics at a secondary care hospital. Information relating to education received, awareness of hypoglycaemia and associated risk factors was collected using a standard questionnaire. Additionally, data regarding demographics, treatment regimes, patient attitudes, hypoglycaemic awareness and risks and barriers to self-management of diabetes was collected. Patients were categorised as low, moderate and high risk based on their responses. Independent sample t-tests and Analysis of Variance were carried out to identify factors contributing to high hypoglycaemic risk. Results: Overall, 70% of the patients reported receiving education about hypoglycaemia from health professionals and 95% of them reported good understanding of hypoglycaemia and were able to self-test. Proportion of women receiving education was, however, lower than men (52% women versus 88% men). Compared with men, women were less likely to recognise (59 versus 73%), or act appropriately to a hypoglycaemic episode (59 versus 78%). The mean number of hypoglycaemic episodes per year (41 versus 12) and the duration of hypoglycaemia (9.9 versus 6.3 min) was also greater among women compared with men. The duration of diabetes (P = 0.018), female gender, type 1 diabetes (0.002) and lack awareness of medications causing hypos (P = 0.006) were strong predictors of hypoglycaemia risk. Conclusions: There are significant gaps in education around hypoglycaemia in older people with diabetes. Women, people with longer duration and type 1 diabetes in particular, need additional attention and future educational initiatives need to address these issues.  

A lean termelési rendszer munkásokra gyakorolt hatása (Effects of lean production on quality of working life from workers’ point of view)

A lean termelési rendszer munkásokra gyakorolt hatásaival foglalkozó irodalomban nincsen egyetértés annak megítélésében, hogy a hatásokban a negatív vagy pozitív hatások dominálnak-e. A szerző tanulmánya ehhez a vitához a pszichológiai, egészségügyi, munkahelyi jellemzőkre és a dolgozói elégedettségre vonatkozó eredmények áttekintésével kapcsolódik. A munkások elégedettségének vizsgálata arra utal, hogy a lean termelési rendszer egyszerre növeli és csökkenti is az elégedettséget, így az összességében nem változik más termelési rendszerekhez képest. A lean termelés kritikusai azt hangsúlyozzák, hogy a többi tényező negatívan hat a munkásokra. Megállapításaik megalapozottsága a nagyon kevés empirikus munka miatt megkérdőjelezhető. Ugyanakkor a tevékenységmenedzsment kutatói érdemben nem tudják cáfolni a stressz, a sérülések és betegségek kockázatának növekedését és a munka intenzívebbé válását. A negatív hatások és a várt pozitív hatások hiányának kiemelése felveti, hogy a munkavállalók bevonásán alapuló lean termelési rendszer nehezen ültethető át a gyakorlatba, illetve hogy a lean termelés intenzifikáción alapuló modellje is elterjedt. _____________ This literature review contributes to the debate related to the effects of lean production on workers. The study reviews different dimensions of the debate and focuses on issues like worker’s satisfaction, psychological effects, health and safety aspects, and workplace characteristics. Findings of researches reviewed in this paper cannot confirm that from workers’ point of view lean production is better than other production initiatives. Lean production enhances and decreases worker’s satisfaction at the same time, altogether, the satisfaction of workers does not change significantly compared to other systems. The negative impact of the other factors (psychological etc.) on workers is usually emphasized in the critique of lean production. Although, the limited number of (empirical) studies doubts these critical voices. However, Operations Management can not reject negative effects like increasing level of stress, increased risks of health and safety problems or intensification of work. The emphasis of the negative effects and the lack of positive effects can refer to the difficult employment of lean involvement system, or simply reflect that the model of lean intensification system is widely spread.

Evaluation of corporate environmental management approaches: A framework and application

This article proposes a framework to evaluate corporate environmental strategies. In the proposed framework, a company's environmental risks are analyzed on two dimensions, One dimension, the endogenous environmental risks, arises from the internal operations of the company. The other dimension, the exogenous environmental risks, are determined by the company's external world: its location, its ecological setting, and the demographic characteristics of the physical environment in which it operates. Four environmental management approaches are defined as a function of endogenous and exogenous environmental risks: reactive, proactive, strategic, and crisis preventive. The framework was applied in a survey of 141 company representatives in Hungary. A relationship was sought between the a priori defined environmental management approaches based on technology and location and the companies' environmental management characteristics defined by senior managers. Variables that differentiated among the four environmental management approaches were identified and ranked. The study concludes that there is a relatively well-defined relationship between the environmental risks of companies and the nature of their environmental management approaches, Implementing a strategic environmental management approach may not be the best option for all companies - although there is a growing pressure to do so.

A disztribúció kiszervezéséhez kapcsolódó ellátási és működési kockázatok (Supply and operational risks in the outsourcing of distribution management)

A cikk célja, hogy elemző bemutatását adja az ellátási láncok működéséhez, különösen a disztribúciós tevékenység kiszervezéséhez kapcsolódó működési kockázatoknak. Az írás első része az irodalomkutatás eredményeit feldolgozva az ellátási láncok kockázati kitettségének növekedése mögött rejlő okokat törekszik feltárni, s röviden bemutatja a vállalati kockázatkezelés lehetséges lépéseit e téren. A cikk második gondolati egysége mélyinterjúk segítségével összefoglalja és rendszerezi a disztribúció kiszervezéséhez kapcsolódó kockázatokat, számba veszi a kapcsolódó kockázatkezelési lehetőségeket, s bemutatja a megkérdezett vállalatok által alkalmazott kockázat-megelőzési alternatívákat. ______ The aim of this paper is to introduce operational risks of supply chains, especially risks deriving from the outsourcing of distribution management. Based on literature review the first part of the paper talks about the potential reasons of increasing global supply chain risks, and the general business activities of risk assessment. Analyzing the results of semi-structured qualitative interviews, the second part summarizes the risks belonging to the outsourcing of distribution and introduces the potential risk assessment and avoidance opportunities and alternatives in practice.

Perceptions of French and Creole Among First-Generation Adult Haitian English Language Learners

Context: Due to a unique combination of factors, outdoor athletes in the Southeastern United States are at high risk of lightning deaths and injuries. Lightning detection methods are available to minimize lightning strike victims. Objective: Becoming aware of the risk factors that predispose athletes to lightning strikes and determining the most reliable detection method against hazardous weather will enable Certified Athletic Trainers to develop protocols that protect athletes from injury. Data Sources: A comprehensive literature review of Medline and Pubmed using key words: lightning, lightning risk factors, lightning safety, lightning detection, and athletic trainers and lightning was completed. Data Synthesis: Factors predisposing athletes to lighting death or injury include: time of year, time of day, the athlete’s age, geographical location, physical location, sex, perspiration level, and lack of education and preparedness by athletes and staff. Although handheld lightning detectors have become widely accessible to detect lightning strikes, their performance has not been independently or objectively confirmed. There is evidence that these detectors inaccurately detect strike locations by recording false strikes and not recording actual strikes. Conclusions: Lightning education and preparation are two factors that can be controlled. Measures need to be taken by Certified Athletic Trainers to ensure the safety of athletes during outdoor athletics. It is critical for athletic trainers and supervising staff members to become fully aware of the risks of lightning strikes in order to most effectively protect everyone under their supervision. Even though lightning detectors have been manufactured in an attempt to minimize death and injuries due to lightning strikes, none of the detectors have been proven to be 100% effective. Educating coaches, athletes, and parents on the risks of lightning and the detection methods available, while implementing an emergency action plan for lightning safety, is crucial to ensure the well being of the student-athlete population.

ANALYSIS OF HYPORHEIC FLOW INDUCED BY A BAR IN A GRAVEL STREAM: AN EXPERIMENTAL STUDY

Pipelines are one of the safest means to transport crude oil, but are not spill-free. This is of concern in North America, due to the large volumes of crude oil shipped by Canadian producers and the lengthy network of pipelines. Each pipeline crosses many rivers, supporting a wide variety of human activities, and rich aquatic life. However, there is a knowledge gap on the risks of contamination of river beds due to oil spills. This thesis addresses this knowledge gap by focussing on mechanisms that transport water (and contaminants) from the free surface flow to the bed sediments, and vice-versa. The work focuses on gravel rivers, in which bed sediments are sufficiently permeable that pressure gradients caused by the interactions of flow with topographic elements (gravel bars), or changes in direction induce exchanges of water between the free surface flow and the bed, known as hyporheic flows. The objectives of the thesis are: to present a new method to visualize and quantify hyporheic flows in laboratory experiments; to conduct a novel series of experiments on hyporheic flow induced by a gravel bar under different free surface flows. The new method to quantify hyporheic flows rests on injections of a solution of dye and water. The method yielded accurate flow lines, and reasonable estimates of the hyporheic flow velocities. The present series of experiments was carried out in a 11 m long, 0.39 m wide, and 0.41 m deep tilting flume. The gravel had a mean particle size of 7.7 mm. Different free surface flows were imposed by changing the flume slope and flow depth. Measured hyporheic flows were turbulent. Smaller free surface flow depths resulted in stronger hyporheic flows (higher velocities, and deeper dye penetration into the sediment). A significant finding is that different free surface flows (different velocities, Reynolds number, etc.) produce similar hyporheic flows as long as the downstream hydraulic gradients are similar. This suggests, that for a specified bar geometry, the characteristics of the hyporheic flows depend on the downstream hydraulic gradients, and not or only minimally on the internal dynamics of the free surface flow.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Appropriate Polypharmacy and Medicine Safety: When Many is not Too Many

The use of multiple medicines (polypharmacy) is increasingly common in middle-aged and older populations. Ensuring the correct balance between the prescribing of ‘many’ drugs and ‘too many’ drugs is a significant challenge. Clinicians are tasked with ensuring that patients receive the most appropriate combinations of medications based on the best available evidence, and that medication use is optimised according to patients’ clinical needs (appropriate polypharmacy). Historically, polypharmacy has been viewed negatively because of the associated medication safety risks, such as drug interactions and adverse drug events. More recently, polypharmacy has been identified as a risk factor for under-prescribing, such that patients do not receive necessary medications and this can also pose risks to patients’ safety and well-being. The negative connotations that have long been associated with the term polypharmacy could potentially be acting as a driving factor for under-prescribing, whereby clinicians are reluctant to prescribe necessary medicines for patients who are already receiving ‘many’ medicines. It is now recognised that the prescribing of ‘many’ medicines can be entirely appropriate in patients with several chronic conditions and that the risks of adverse drug events that have been associated with polypharmacy may be greatly reduced when patients’ clinical context is taken into consideration. In this article, we outline the current perspectives on polypharmacy and make the case for adopting the term ‘appropriate polypharmacy’ in differentiating between the prescribing of ‘many’ drugs and ‘too many’ drugs. We also outline the inherent challenges in doing so and provide recommendations for future clinical practice and research.

Waste Not, Want Not: Managing Perishables in Small and Medium Retail Enterprises

Purpose of this paper:
Recent literature indicates that around one third of perishable products finish as waste (Mena et al., 2014): 60% of this waste can be classified as avoidable (EC, 2010) suggesting logistics and operational inefficiencies along the supply chain. In developed countries perishable products are predominantly wasted in wholesale and retail (Gustavsson et al., 2011) due to customer demand uncertainty the errors and delays in the supply chain (Fernie and Sparks, 2014). While research on logistics of large retail supply chains is well documented, research on retail small and medium enterprises’ (SMEs) capabilities to prevent and manage waste of perishable products is in its infancy (c.f. Ellegaard, 2008) and needs further exploration. In our study, we investigate the retail logistics practice of small food retailers, the factors that contribute to perishable products waste and the barriers and opportunities of SMEs in retail logistics to preserve product quality and participate in reverse logistics flows.

Design/methodology/approach:
As research on waste of perishable products for SMEs is scattered, we focus on identifying key variables that contribute to the creation of avoidable waste. Secondly we identify patterns of waste creation at the retail level and its possibilities for value added recovery. We use explorative case studies (Eisenhardt, 1989) and compare four SMEs and one large retailer that operate in a developed market. To get insights into specificities of SMEs that affect retail logistics practice, we select two types of food retailers: specialised (e.g. greengrocers and bakers) and general (e.g. convenience store that sells perishable products as a part of the assortment)

Findings:
Our preliminary findings indicate that there is a difference between large retailers and SME retailers in factors that contribute to the waste creation, as well as opportunities for value added recovery of products. While more factors appear to affect waste creation and management at large retailers, a small number of specific factors appears to affect SMEs. Similarly, large retailers utilise a range of practices to reduce risks of product perishability and short shelf life, manage demand, and manage reverse logistics practices. Retail SMEs on the other hand have limited options to address waste creation and value added recovery. However, our findings show that specialist SMEs could successfully minimize waste and even create possibilities for value added recovery of perishable products. Data indicates that business orientation of the SME, the buyersupplier relationship, and an extent of adoption of lean principles in retail coupled with SME resources, product specific regulations and support from local authorities for waste management or partnerships with other organizations determine extent of successful preservation of a product quality and value added recovery.

Value:
Our contribution to the SCM academic literature is threefold: first, we identify major factors that contribute to the generation waste of perishable products in retail environment; second, we identify possibilities for value added recovery for perishable products and third, we present opportunities and challenges for SME retailers to manage or participate in activities of value added recovery. Our findings contribute to theory by filling a gap in the literature that considers product quality preservation and value added recovery in the context of retail logistics and SMEs.

Research limitations/implications:
Our findings are limited to insights from five case studies of retail companies that operate within a developed market. To improve on generalisability, we intend to increase the number of cases and include data obtained from the suppliers and organizations involved in reverse logistics flows (e.g. local authorities, charities, etc.).

Practical implications:
With this paper, we contribute to the improvement of retail logistics and operations in SMEs which constitute over 99% of business activities in UK (Rhodes, 2015). Our findings will help retail managers and owners to better understand the possibilities for value added recovery, investigate a range of logistics and retail strategies suitable for the specificities of SME environment and, ultimately, improve their profitability and sustainability.