Adverse hypersensitivity reactions to mesna as adjunctive therapy for cyclophosphamide

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Fabrication of novel metal alloy foams for biomedical applications

Degeneration of the weight bearing bones of the ageing population often requires the inception of metallic biomaterials. Research in this area is receiving increased attention globally. However, most of today's artificial bone materials are dense and suffer from problems of adverse reaction, biomechanical mismatch and lack of appropriate space for the regeneration of new bone tissues. In the present study, novel ZrTi alloy foams with a porous structure and mechanical properties that are very close to those of bone were fabricated. These ZrTi alloy foams are biocompatible, and display a porous structure permitting the ingrowth of new bone tissues.

Biomimetic porous titanium scaffolds for orthopaedic and dental applications

The development of artificial organs and implants for replacement of injured and diseased hard tissues such as bones, teeth and joints is highly desired in orthopedic surgery. Orthopedic prostheses have shown an enormous success in restoring the function and offering high quality of life to millions of individuals each year. Therefore, it is pertinent for an engineer to set out new approaches to restore the normal function of impaired hard tissues.

Over the last few decades, a large number of metals and applied materials have been developed with significant improvement in various properties in a wide range of medical applications. However, the traditional metallic bone implants are dense and often suffer from the problems of adverse reaction, biomechanical mismatch and lack of adequate space for new bone tissue to grow into the implant. Scientific advancements have been made to fabricate porous scaffolds that mimic the architecture and mechanical properties of natural bone. The porous structure provides necessary framework for the bone cells to grow into the pores and integrate with host tissue, known as osteointegration. The appropriate mechanical properties, in particular, the low elastic modulus mimicking that of bone may minimize or eliminate the stress-shielding problem. Another important approach is to develop biocompatible and corrosion resistant metallic materials to diminish or avoid adverse body reaction. Although numerous types of materials can be involved in this fast developing field, some of them are more widely used in medical applications. Amongst them, titanium and some of its alloys provide many advantages such as excellent biocompatibility, high strength-to-weight ratio, lower elastic modulus, and superior corrosion resistance, required for dental and orthopedic implants. Alloying elements, i.e. Zr, Nb, Ta, Sn, Mo and Si, would lead to superior improvement in properties of titanium for biomedical applications.

New processes have recently been developed to synthesize biomimetic porous titanium scaffolds for bone replacement through powder metallurgy. In particular, the space holder sintering method is capable of adjusting the pore shape, the porosity, and the pore size distribution, notably within the range of 200 to 500 m as required for osteoconductive applications. The present chapter provides a review on the characteristics of porous metal scaffolds used as bone replacement as well as fabrication processes of porous titanium (Ti) scaffolds through a space holder sintering method. Finally, surface modification of the resultant porous Ti scaffolds through a biomimetic chemical technique is reviewed, in order to ensure that the surfaces of the scaffolds fulfill the requirements for biomedical applications.

Reducing adverse events in older Australians taking newly released drugs

The number of older Australians with one or multiple chronic diseases is increasing. This thesis presents a model to assist in identifying current older patients with multiple illnesses and taking multiple medications who are at risk of experiencing an adverse drug reaction if they are prescribed a newly released drug.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians : a model process

Background
The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients.

Methods
The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug.

Results
Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug.

Conclusions
Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.

Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Exploring in-hospital adverse drug events using ICD-10 codes

 Abstract
Objective Adverse drug events (ADEs) during hospital admissions are a widespread problem associated with adverse patient outcomes. The ‘external cause’ codes in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) provide opportunities for identifying the incidence of ADEs acquired during hospital stays that may assist in targeting interventions to decrease their occurrence. The aim of the present study was to use routine administrative data to identify ADEs acquired during hospital admissions in a suburban healthcare network in Melbourne, Australia.

Methods Thirty-nine secondary diagnosis fields of hospital discharge data for a 1-year period were reviewed for ‘diagnoses not present on admission’ and assigned to the Classification of Hospital Acquired Diagnoses (CHADx) subclasses. Discharges with one or more ADE subclass were extracted for retrospective analysis.

Results From 57 205 hospital discharges, 7891 discharges (13.8%) had at least one CHADx, and 402 discharges (0.7%) had an ADE recorded. The highest proportion of ADEs was due to administration of analgesics (27%) and systemic antibiotics (23%). Other major contributors were anticoagulation (13%), anaesthesia (9%) and medications with cardiovascular side-effects (9%).

Conclusion Hospital data coded in ICD-10 can be used to identify ADEs that occur during hospital stays and also clinical conditions, therapeutic drug classes and treating units where these occur. Using the CHADx algorithm on administrative datasets provides a consistent and economical method for such ADE monitoring.

What is known about the topic? Adverse drug events (ADEs) can result in several different physical consequences, ranging from allergic reactions to death, thereby posing a significant burden on patients and the health system. Numerous studies have compared manual, written incident reporting systems used by hospital staff with computerised automated systems to identify ADEs acquired during hospital admissions. Despite various approaches aimed at improving the detection of ADEs, they remain under-reported, as a result of which interventions to mitigate the effect of ADEs cannot be initiated effectively.

What does this paper add? This research article demonstrates major methodological advances over comparable published studies looking at the effectiveness of using routine administrative data to monitor rates of ADEs that occur during a hospital stay and reviews the type of ADEs and their frequency patterns during patient admission. It also provides an insight into the effect of ADEs that occur within different hospital treating units. The method implemented in this study is unique because it uses a grouping algorithm developed for the Australian Commission on Safety and Quality in Health Care (ACSQHC) to identify ADEs not present on admission from patient data coded in ICD-10. This algorithm links the coded external causes of ADEs with their consequences or manifestations. ADEs identified through the use of programmed code based on this algorithm have not been studied in the past and therefore this paper adds to previous knowledge in this subject area.

What are the implications for health professionals? Although not all ADEs can be prevented with current medical knowledge, this study can assist health professionals in targeting interventions that can efficiently reduce the rate of ADEs that occur during a hospital stay, and improve information available for future medication management decisions.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process

BACKGROUND: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. METHODS: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. RESULTS: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. CONCLUSIONS: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).