Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery : a review for multidisciplinary researchers

Pulmonary drug delivery is the focus of much research and development because of its great potential to produce maximum therapeutic benefit. Among the available options the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse number of diseases. However, as drug delivery from a DPI involves a complicated set of physical processes and the integration of drug formulations, device design and patient usage, the engineering development of this medical technology is proving to be a great challenge. Currently there is large range of devices that are either available on the market or under development, however, none exhibit superior clinical efficacy. A major concern is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs. The extent of variability depends on the drug formulation, the device design and the patient’s inhalation profile. This article reviews recent advances in DPI technology and presents the key factors which motivate and constrain the successful engineering of a universal, patient-independent DPI that is capable of efficient, reliable and repeatable drug delivery. A strong emphasis is placed on the physical processes of drug powder aerosolisation, deagglomeration, and dispersion and on the engineering of formulations and inhalers that can optimise these processes.

Early users of fertility treatment with hormones and IVF : women who live in major cities and have private health insurance

Objective: To identify early users (women aged <34 years) of fertility treatment with hormones and in vitro fertilisation (IVF). Methods: A cross-sectional survey of infertile women from fertility clinics (n=59) and from the community (Australian Longitudinal Study on Women's Health participants) who had (n=121) or had not (n=110) used hormones/IVF as treatment for infertility. Associations between socio-demographic, reproductive and lifestyle factors, medical conditions and recurrent symptoms and using treatment (or not) were analysed using multivariable logistic regression. Results: Among infertile women who had used treatment (community vs clinic), women from clinics had lower odds of living outside major cities, using hormones only, i.e., not IVF, or recurrent headaches/migraines, severe tiredness, or stiff/painful joints; and higher odds of recent diagnoses of urinary tract infection or anxiety disorder. Compared to infertile women who had not used treatment, women from clinics had lower odds of living outside major cities, recurrent allergies or severe tiredness; and higher odds of having private health insurance for hospital or ancillary services, recent diagnosis of polycystic ovary syndrome or recurrent constipation. Conclusions: Compared to infertile women in the community, living in major cities and having private health insurance are associated with early use of treatment for infertility at specialist clinics by women aged <34 years. Implications: These results provided evidence of inequity of services for infertile women.

The effect of alcohol and drug consumption on academic performance : a treatment effect evaluation

It is often argued that consumption of alcohol, tobacco and drugs is detrimental to the cognitive abilities of teenagers. In order to disentangle a possible causal effect of these substances use from a self-selection bias, we control for pupils previous performance and for their previous rate of progression applying a DiDiD strategy. Using the NELS 1988 panel dataset, we find that the effects of alcohol and tobacco on test scores disappear once the selection bias is controlled for (this does not preclude long term detrimental effects). However, we find reliable evidence that heavy use of drugs (marijuana and cocaine) has direct detrimental effects on educational achievements. Hence, our results may have significant policy implications.

An interactive and adaptive building layer : strategies for allowing people to become advanced building-users

This paper reports outcomes of a pilot study to develop a conceptual framework to allow people to retrofit a building-layer to gain better control of their own built- environments. The study was initiated by the realisation that discussions surrounding the improvement of building performances tend to be about top-down technological solutions rather than to help and encourage bottom-up involvement of building-users. While users are the ultimate beneficiaries and their feedback is always appreciated, their direct involvements in managing buildings would often be regarded as obstruction or distraction. This is largely because casual interventions by uninformed building-users tend to disrupt the system. Some earlier researches showed however that direct and active participation of users could improve the building performance if appropriate training and/or systems were introduced. We also speculate this in long run would also make the built environment more sustainable. With this in mind, we looked for opportunities to retrofit our own office with an interactive layer to study how we could introduce ad-hoc systems for building-users. The aim of this paper is to describe our vision and initial attempts followed by discussion.

Emergency Health Services (EHS) : demand and service delivery models. [Monograph 2 : Queensland EHS users’ profile]

Emergency health is a critical component of Australia’s health system and one which is increasingly congested from growing demand and blocked access to inpatient beds. The Emergency Health Services Queensland (EHSQ) study aims to identify the factors driving increased demand for emergency health and to evaluate strategies which may safely reduce the future demand growth. This monograph addresses the characteristics of users of emergency health services with an aim to identify those that appear to contribute to demand growth. This study utilises data on patients treated by Emergency Departments (ED) and Queensland Ambulance Service (QAS) across Queensland. ED data was derived from the Emergency Department Information System (EDIS) for the period 2001-02 through to 2010-11. Ambulance data was extracted from the QAS’ Ambulance Information Management System (AIMS) and electronic Ambulance Report Form (eARF) for the period 2001-02 through to 2009-10. Due to discrepancies and comparability issues for ED data, this monograph compares data from the 2003-04 time period with 2010-11 data for 21 of the reporting EDs. Also a snapshot of users for the 2010-11 financial year for 31 reporting EDs is used to describe the characteristics of users and to compare those characteristics with population demographics. For QAS data, the 2002-03 and 2009-10 time periods were selected for detailed analyses to identify trends. • Demand for emergency health care services is increasing, representing both increased population and increased relative utilisation. Per capita demand for ED attention has increased by 2% per annum over the last decade and for ambulance attention by 3.7% per annum. • The growth in ED demand is prominent in more urgent triage categories with actual decline in less urgent patients. An estimated 55% of patients attend hospital EDs outside of normal working hours. There is no evidence that patients presenting out of hours are significantly different to those presenting within working hours; they have similar triage assessments and outcomes. • Patients suffering from injuries and poisoning comprise 28% of the ED workload (an increase of 65% in the study period), whilst declines of 32% in cardiovascular and circulatory conditions, and musculoskeletal problems have been observed. • 25.6% of patients attending EDs are admitted to hospital. 19% of admitted patients and 7% of patients who die in the ED are triage category 4 or 5 on arrival. • The average age of ED patients is 35.6 years. Demand has grown in all age groups and amongst both men and women. Men have higher utilisation rates for ED in all age groups. The only group where the growth rate in women has exceeded men is in the 20-29 age group; this growth is particularly in the injury and poisoning categories. • Considerable attention has been paid publicly to ED performance criteria. It is worth noting that 50% of all patients were treated within 33 minutes of arrival. • Patients from lower socioeconomic areas appear to have higher utilisation rates and the utilisation rate for indigenous people appears to exceed those of European and other backgrounds. The utilisation rates for immigrant people is generally less than that of Australian born however it has not been possible to eliminate the confounding impact of different age and socioeconomic profiles. • Demand for ambulance service is also increasing at a rate that exceeds population growth. Utilisation rates have increased by an average of 5% per annum in Queensland compared to 3.6% nationally, and the utilisation rate in Queensland is 27% higher than the national average. • The growth in ambulance utilisation has also been amongst the more urgent categories of dispatch and utilisation rates are higher in rural and regional areas than in the metropolitan area. The demand for ambulance increases with age but the growth in demand for ambulance service has been more prominent in younger age groups. These findings contribute significantly to an understanding of the growth in demand for emergency health. It shows that the growth is amongst patients in genuine need of emergency healthcare and public rhetoric that the congestion of emergency health services is due to inappropriate attendees is unable to be substantiated. The consistency of the growth in demand over the last decade reflects not only the changing demographics of the Australian population but also the changes in health status, standards of acute health care and other social factors. The growth is also amongst patients with acute injury and poisoning which is inconsistent with rates of chronic disease as a fundamental driver. We have also interviewed patients in regard to their decision making choices for acute health care and the factors that influence these decisions and this will be the subject of a third Monograph and publications.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

Subacute effects of ecstasy on mood : an exploration of associated risk factors

Ecstasy use may result in lowered mood, anxiety or aggression in the days following use. Yet, few studies have investigated what factors increase the risk of experiencing such symptoms. Ecstasy users (at least once in the last 12 months) who subsequently took ecstasy (n=35) over the next week, were compared on measures of mood, sleep, stress and drug use, with those who abstained (n=21) that week. Measures were administered the week prior to ecstasy use and 1 and 3 days following use, or the equivalent day for abstainers. Mood symptoms were assessed using the Kessler-10 self-report psychological distress scale, a subjective mood rating (1-10), and the depression, anxiety and hostility items of the clinician-rated Brief Psychiatric Rating Scale. Timeline followback methods were used to collect information on drug use and life stress in the past month. Self-reported sleep quality was also assessed. Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms. Rather, lowered mood and increased psychological distress were associated with self-reported hours and quality of sleep obtained during the 3-day follow up. These findings highlight the importance of considering sleep disruption in understanding the short-term mood effects of ecstasy use.

Drug abusers perceptions of their parents.

Many clinicians in the area of drug addiction believe that emotional problems arise from particular styles of parenting. To investigate this link, 63 young male and female addicts who had sought treatment completed the Parental Bonding Instrument which tapped their perceptions of their relationship with each parent. Addicts reported early parental experiences differing from those of a control group. Drug abusers judged their parents as cold, indifferent, controlling and intrusive. In addition, these perceptions were shared by male and female addicts. These results, together with previous research suggest that these perceptions might well point to a general risk factor for the development of a broad range of psychological and psychiatric disorders. In addition, the issue of family factors in the design and implementation of drug treatment programs needs to be addressed.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

The continuing relevance of the library as a third place for users and non-users of IT : the case of Canada Bay

The purpose of this paper is to consider how libraries support the development of community networks both physically and digitally. To do this, a case-study methodology was employed, including a combination of data about the library and qualitative interviews with library users considering their experience of the library. This paper proposes that libraries act as ‘third places’ spatially connecting people; libraries also build links with online media and play a critical role in inclusively connecting non-technology users with the information on the Internet and digital technology more generally. The paper establishes the value of libraries in the digital age and recommends that libraries actively seek ways to develop links between non-technology users and activity on the Internet. It addresses the need to reach these types of non-technology users in different ways. Further, it suggests that libraries utilise their positioning as third places to create broader community networks, to support local communities beyond existing users and beyond the library precinct.

Dry powder inhaler formulations : effect of carrier size on the drug dispersion

Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Social cars : sensing, gathering, sharing and conveying social cues to road users

Intelligent Transport Systems (ITS) resembles the infrastructure for ubiquitous computing in the car. It encompasses a) all kinds of sensing technologies within vehicles as well as road infrastructure, b) wireless communication protocols for the sensed information to be exchanged between vehicles (V2V) and between vehicles and infrastructure (V2I), and c) appropriate intelligent algorithms and computational technologies that process these real-time streams of information. As such, ITS can be considered a game changer. It provides the fundamental basis of new, innovative concepts and applications, similar to the Internet itself. The information sensed or gathered within or around the vehicle has led to a variety of context-aware in-vehicular technologies within the car. A simple example is the Anti-lock Breaking System (ABS), which releases the breaks when sensors detect that the wheels are locked. We refer to this type of context awareness as vehicle/technology awareness. V2V and V2I communication, often summarized as V2X, enables the exchange and sharing of sensed information amongst cars. As a result, the vehicle/technology awareness horizon of each individual car is expanded beyond its observable surrounding, paving the way to technologically enhance such already advanced systems. In this chapter, we draw attention to those application areas of sensing and V2X technologies, where the human (driver), the human’s behavior and hence the psychological perspective plays a more pivotal role. The focal points of our project are illustrated in Figure 1: In all areas, the vehicle first (1) gathers or senses information about the driver. Rather than to limit the use of such information towards vehicle/technology awareness, we see great potential for applications in which this sensed information is then (2) fed back to the driver for an increased self-awareness. In addition, by using V2V technologies, it can also be (3) passed to surrounding drivers for an increased social awareness, or (4), pushed even further, into the cloud, where it is collected and visualized for an increased, collective urban awareness within the urban community at large, which includes all city dwellers.