Biodegradable polymers as drug delivery systems.

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Experimental and theoretical studies on molecular geometry and polymorphism in crystalline drug substances

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Biodegradable polymers as drug delivery systems

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Warfarin toxicity: do discharge ICD-10 codes and yellow cards accurately identify serious adverse drug reactions?

Focal points: ICD-10 codings and spontaneous yellow card reports for warfarin toxicity were compared retrospectively over a one-year period Eighteen cases of ICD-10 coded warfarin toxicity were identified from a total of 55,811 coded episodes More than three times as many ADRs to warfarin were found by screening ICD-10 codes as were reported spontaneously using the yellow card scheme Valuable information is being lost to regulatory authorities and as recognised reporters to the yellow card scheme, pharmacists are well placed to report these ADRs, enhancing their role in the safe and appropriate prescribing of warfarin

Set-up and maintenance of syringe drivers for subcutaneous drug administration in palliative care

Focal points: Details of syringe driver use were collected from 11 inpatient hospice units in the West Midlands and compared with predetermined standards set by a multidisciplinary group We recorded 294 syringe driver events which complied with standards for the choice of administration site, protection of the syringe driver from light and the reason for initiation of the infusion Issues of nurse training, variability in prescribing practices, provision of written information for patients, labelling and documentation of the diluent used were all identified as areas in which compliance with standards could be improved

A patient's perspective:the impact of adverse drug reactions on patients and their views on reporting

What is known and objective: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self-reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. Method: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi-structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient's reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients'responses was performed. Results and discussion: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient's 'job'. What is new and conclusion: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic. © 2011 Blackwell Publishing Ltd.

Identification of DNA-binding proteins by incorporating evolutionary information into pseudo amino acid composition via the top-n-gram approach

DNA-binding proteins are crucial for various cellular processes and hence have become an important target for both basic research and drug development. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to establish an automated method for rapidly and accurately identifying DNA-binding proteins based on their sequence information alone. Owing to the fact that all biological species have developed beginning from a very limited number of ancestral species, it is important to take into account the evolutionary information in developing such a high-throughput tool. In view of this, a new predictor was proposed by incorporating the evolutionary information into the general form of pseudo amino acid composition via the top-n-gram approach. It was observed by comparing the new predictor with the existing methods via both jackknife test and independent data-set test that the new predictor outperformed its counterparts. It is anticipated that the new predictor may become a useful vehicle for identifying DNA-binding proteins. It has not escaped our notice that the novel approach to extract evolutionary information into the formulation of statistical samples can be used to identify many other protein attributes as well.

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Patient experiences of serious adverse drug reactions and their attitudes to medicines:a qualitative study of survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK

Background: Adverse drug reactions (ADRs) cause significant morbidity and mortality and account for around 6.5% of hospital admissions. Patient experiences of serious ADRs and their long-term impact on patients' lives, including their influence on current attitudes towards medicines, have not been previously explored. Objective: The aim of the study was to explore the experiences, beliefs, and attitudes of survivors of serious ADRs, using drug-induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) as a paradigm. Methods: A retrospective, qualitative study was undertaken using detailed semi-structured interviews. Fourteen adult survivors of SJS and TEN, admitted to two teaching hospitals in the UK, one the location of a tertiary burns centre, were interviewed. Interview transcripts were independently analysed by three different researchers and themes emerging from the text identified. Results: All 14 patients were aware that their condition was drug induced, and all but one knew the specific drug(s) implicated. Several expressed surprise at the perceived lack of awareness of the ADR amongst healthcare professionals, and described how the ADR was mistaken for another condition. Survivors believed that causes of the ADR included (i) being given too high a dose of the drug; (ii) medical staff ignoring existing allergies; and (iii) failure to monitor blood tests. Only two believed that the reaction was unavoidable. Those who believed that the condition could have been avoided had less trust in healthcare professionals. The ADR had a persisting impact on their current lives physically and psychologically. Many now avoided medicines altogether and were fearful of becoming ill enough to need them. © 2011 Adis Data Information BV. All rights reserved. Conclusions: Life-threatening ADRs continued to affect patients’ lives long after the event. Patients’ beliefs regarding the cause of the ADR differed, and may have influenced their trust in healthcare professionals and medicines. We propose that clear communication during the acute phase of a serious ADR may therefore be important.

Qualitative Responses to Pre-employment Drug Testing in the Foodservice Industry

Employee substance abuse has long time been a topic of concern for the hospitality industry. Operating under the assumption that drug-users, and associated undesirable behavior, can be eliminated from the hiring process, many operations have adopted pre-employment drug-testing policies. Despite being represented across the industry as a major target of effort and resources, it is suggested that the perceived sensitive-nature of the subject has somewhat hindered access to qualitative information. The purpose of this research was to assess and explore the attitudes, beliefs and perceptions of both management and employees in the foodservice industry regarding pre-employment drug-testing and its impact on work performance. Through the use of a phenomenological survey, qualitative data was collected then used to identify themes in participants’ perceptions of such screening policies and their effects. Results and implications of these findings are discussed.

Drug Abuse in the Hospitality Industry

Drug and alcohol abuse in the hospitality industry is an ongoing problem, reflective of business as a whole. A series of surveys were conducted at national drug rehabilitation centers seeking information from patients currently or formerly employed in the hotel and restaurant industry. The author identifies a number of problem indicators and makes recommendations relevant to resolutions.

Online information seeking by patients with bipolar disorder:results from an international multisite survey

Background: Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods: A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results: 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion: Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites.

Patient/carers' recollection of medicines related information from an out-patient clinic appointment

AIM: To identify what medicines related information children/young people or their parents/carers are able to recall following an out-patient clinic appointment. METHOD: A convenience sample of patients' prescribed at least one new long-term (>6 weeks) medicine were recruited from a single UK paediatric hospital out-patient pharmacy. A face-to-face semi-structured questionnaire was administered to participants when they presented with their prescription. The questionnaire included the following themes: names of the medicines, therapeutic indication, dose regimen, duration of treatment and adverse effects.The results were analysed using Microsoft Excel 2013. RESULTS: One hundred participants consented and were included in the study. One hundred and forty-five medicines were prescribed in total. Participants were able to recall the names of 96 (66%) medicines and were aware of the therapeutic indication for 142 (97.9%) medicines. The dose regimen was accurately described for 120 (82.8%) medicines with the duration of treatment known for 132 (91%). Participants mentioned that they had been advised about side effects for 44 (30.3%) medicines. Specific counselling points recommended by the BNFc1, were either omitted or not recalled by participants for the following systemic treatments: cetirizine (1), chlorphenamine (1), desmopressin (2), hydroxyzine (2), itraconazole (1), piroxicam (2), methotrexate (1), stiripentol (1) and topiramate (1). CONCLUSION: Following an out-patient consultation, where a new medicine is prescribed, children and their parents/carers are usually able to recall the indication, dose regimen and duration of treatment. Few were able to recall, or were told about, possible adverse effects. This may include some important drug specific effects that require vigilance during treatment.Patients, along with families and carers, should be involved in the decision to prescribe a medicine.2 This includes a discussion about the benefits of the medicine on the patient's condition and possible adverse effects.2 Treatment side effects have been shown to be a factor in treatment non-adherence in paediatric long-term medical conditions.3 Practitioners should explain to patients, and their family members or carers where appropriate, how to identify and report medicines-related patient safety incidents.4 However, this study suggests that medical staff may not be comfortable discussing the adverse effects of medicines with patients or their parents/carers.Further research in to the shared decision making process in the paediatric out-patient clinic when a new long-term medicine is prescribed is required to further support medicines adherence and the patient safety agenda.

Mechanistic Models of Anti-HIV Microbicide Drug Delivery

A new modality for preventing HIV transmission is emerging in the form of topical microbicides. Some clinical trials have shown some promising results of these methods of protection while other trials have failed to show efficacy. Due to the relatively novel nature of microbicide drug transport, a rigorous, deterministic analysis of that transport can help improve the design of microbicide vehicles and understand results from clinical trials. This type of analysis can aid microbicide product design by helping understand and organize the determinants of drug transport and the potential efficacies of candidate microbicide products.

Microbicide drug transport is modeled as a diffusion process with convection and reaction effects in appropriate compartments. This is applied here to vaginal gels and rings and a rectal enema, all delivering the microbicide drug Tenofovir. Although the focus here is on Tenofovir, the methods established in this dissertation can readily be adapted to other drugs, given knowledge of their physical and chemical properties, such as the diffusion coefficient, partition coefficient, and reaction kinetics. Other dosage forms such as tablets and fiber meshes can also be modeled using the perspective and methods developed here.

The analyses here include convective details of intravaginal flows by both ambient fluid and spreading gels with different rheological properties and applied volumes. These are input to the overall conservation equations for drug mass transport in different compartments. The results are Tenofovir concentration distributions in time and space for a variety of microbicide products and conditions. The Tenofovir concentrations in the vaginal and rectal mucosal stroma are converted, via a coupled reaction equation, to concentrations of Tenofovir diphosphate, which is the active form of the drug that functions as a reverse transcriptase inhibitor against HIV. Key model outputs are related to concentrations measured in experimental pharmacokinetic (PK) studies, e.g. concentrations in biopsies and blood. A new measure of microbicide prophylactic functionality, the Percent Protected, is calculated. This is the time dependent volume of the entire stroma (and thus fraction of host cells therein) in which Tenofovir diphosphate concentrations equal or exceed a target prophylactic value, e.g. an EC50.

Results show the prophylactic potentials of the studied microbicide vehicles against HIV infections. Key design parameters for each are addressed in application of the models. For a vaginal gel, fast spreading at small volume is more effective than slower spreading at high volume. Vaginal rings are shown to be most effective if inserted and retained as close to the fornix as possible. Because of the long half-life of Tenofovir diphosphate, temporary removal of the vaginal ring (after achieving steady state) for up to 24h does not appreciably diminish Percent Protected. However, full steady state (for the entire stromal volume) is not achieved until several days after ring insertion. Delivery of Tenofovir to the rectal mucosa by an enema is dominated by surface area of coated mucosa and whether the interiors of rectal crypts are filled with the enema fluid. For the enema 100% Percent Protected is achieved much more rapidly than for vaginal products, primarily because of the much thinner epithelial layer of the mucosa. For example, 100% Percent Protected can be achieved with a one minute enema application, and 15 minute wait time.

Results of these models have good agreement with experimental pharmacokinetic data, in animals and clinical trials. They also improve upon traditional, empirical PK modeling, and this is illustrated here. Our deterministic approach can inform design of sampling in clinical trials by indicating time periods during which significant changes in drug concentrations occur in different compartments. More fundamentally, the work here helps delineate the determinants of microbicide drug delivery. This information can be the key to improved, rational design of microbicide products and their dosage regimens.

Drug prescribing patterns in the General Medical Services Scheme in Ireland and projected costs to 2026

The primary objective is to investigate the main factors contributing to GMS expenditure on pharmaceutical prescribing and projecting this expenditure to 2026. This study is located in the area of pharmacoeconomic cost containment and projections literature. The thesis has five main aims: 1. To determine the main factors contributing to GMS expenditure on pharmaceutical prescribing. 2. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2006 Central Statistics Office (CSO) Census data and 2007 Health Service Executive{Primary Care Reimbursement Service (HSE{PCRS) sample data. 3. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2012 HSE{PCRS population data, incorporating cost containment measures, and 2011 CSO Census data. 4. To investigate the impact of demographic factors and the pharmacology of drugs (Anatomical Therapeutic Chemical (ATC)) on GMS expenditure. 5. To explore the consequences of GMS policy changes on prescribing expenditure and behaviour between 2008 and 2014. The thesis is centered around three published articles and is located between the end of a booming Irish economy in 2007, a recession from 2008{2013, to the beginning of a recovery in 2014. The literature identified a number of factors influencing pharmaceutical expenditure, including population growth, population aging, changes in drug utilisation and drug therapies, age, gender and location. The literature identified the methods previously used in predictive modelling and consequently, the Monte Carlo Simulation (MCS) model was used to simulate projected expenditures to 2026. Also, the literature guided the use of Ordinary Least Squares (OLS) regression in determining demographic and pharmacology factors influencing prescribing expenditure. The study commences against a backdrop of growing GMS prescribing costs, which has risen from e250 million in 1998 to over e1 billion by 2007. Using a sample 2007 HSE{PCRS prescribing data (n=192,000) and CSO population data from 2008, (Conway et al., 2014) estimated GMS prescribing expenditure could rise to e2 billion by2026. The cogency of these findings was impacted by the global economic crisis of 2008, which resulted in a sharp contraction in the Irish economy, mounting fiscal deficits resulting in Ireland's entry to a bailout programme. The sustainability of funding community drug schemes, such as the GMS, came under the spotlight of the EU, IMF, ECB (Trioka), who set stringent targets for reducing drug costs, as conditions of the bailout programme. Cost containment measures included: the introduction of income eligibility limits for GP visit cards and medical cards for those aged 70 and over, introduction of co{payments for prescription items, reductions in wholesale mark{up and pharmacy dispensing fees. Projections for GMS expenditure were reevaluated using 2012 HSE{PCRS prescribing population data and CSO population data based on Census 2011. Taking into account both cost containment measures and revised population predictions, GMS expenditure is estimated to increase by 64%, from e1.1 billion in 2016 to e1.8 billion by 2026, (ConwayLenihan and Woods, 2015). In the final paper, a cross{sectional study was carried out on HSE{PCRS population prescribing database (n=1.63 million claimants) to investigate the impact of demographic factors, and the pharmacology of the drugs, on GMS prescribing expenditure. Those aged over 75 (ẞ = 1:195) and cardiovascular prescribing (ẞ = 1:193) were the greatest contributors to annual GMS prescribing costs. Respiratory drugs (Montelukast) recorded the highest proportion and expenditure for GMS claimants under the age of 15. Drugs prescribed for the nervous system (Escitalopram, Olanzapine and Pregabalin) were highest for those between 16 and 64 years with cardiovascular drugs (Statins) were highest for those aged over 65. Females are more expensive than males and are prescribed more items across the four ATC groups, except among children under 11, (ConwayLenihan et al., 2016). This research indicates that growth in the proportion of the elderly claimants and associated levels of cardiovascular prescribing, particularly for statins, will present difficulties for Ireland in terms of cost containment. Whilst policies aimed at cost containment (co{payment charges, generic substitution, reference pricing, adjustments to GMS eligibility) can be used to curtail expenditure, health promotional programs and educational interventions should be given equal emphasis. Also policies intended to affect physicians prescribing behaviour include guidelines, information (about price and less expensive alternatives) and feedback, and the use of budgetary restrictions could yield savings.