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Supporting physical activity behaviour change in adults with obstructive sleep apnoea
Background: Low physical activity represents a potentially modifiable risk factor in the management of obstructive sleep apnoea (OSA). The benefits to this population of being more physically active include improved apnoea severity and reduced risk of hypertension, cardiovascular disease, type 2 diabetes and obesity. There is currently little available information regarding the type and level of physical activity undertaken in adults with diagnosed OSA. Moreover, potential barriers to activity have not been explored. Beyond provision of continuous positive airway pressure to manage periods of apnoea, there is limited support available to address lifestyle factors in this population.
Aim: The aim of this thesis was to establish physical activity levels in a cohort of adults with OSA, determine barriers to activity and explore the feasibility of supporting a change in physical activity behaviour in this cohort.
Methods: An initial literature review on physical activity in the population with OSA formed the basis for an exploratory study to determine physical activity levels in a cohort of 60 participants at risk of OSA, recruited from the local Sleep Clinic. Physical activity levels were compared with current World Health Organization guidelines. Levels of inactivity, time engaged in sedentary behaviour and barriers to activity were ascertained. A second literature review explored the use of text messaging as a means of motivation to support physical activity behaviour. A focus group and individual interviews were then conducted to determine the acceptability of motivational text messaging to end users with OSA. Using these findings an intervention study was developed to establish the feasibility of a text messaging intervention in conjunction with personalised exercise prescription to increase physical activity behaviour and increase exercise self-efficacy in a cohort of 30 participants recruited from the Clinic. Individual interviews with a cohort of the participants were then undertaken in an effort to understand the benefits and limitations of the intervention from the participants’ perspective.
Results: From the initial cohort 37% did not meet World Health Organization guidelines for weekly physical activity. This group demonstrated higher rates of hypertension, type 2 diabetes and obesity, and higher levels of sedentary behaviour. Low motivation and pain were the main barriers to activity in those not meeting the physical activity guidelines; 91% reported wanting to be more active. Text messaging was considered an acceptable form of motivation by end-users. The feasibility study showed that text messages offered the potential to support the uptake of physical activity in adults with OSA.
Conclusion: Low levels of physical activity represent an additional risk factor in those at risk of OSA. In our study, although there was recognition of the benefits of being active, lack of motivation was a barrier. A physical activity intervention using telehealth as a motivational component offers a potentially feasible method of supporting physical activity behaviour change in adults with OSA. Addressing lifestyle factors in this population offers a previously unmet need, which could contribute to reducing associated health risks
Towards predictable tuning of spin crossover
Spin crossover (SCO) active metal complexes are highly versatile materials thanks to their sensitivity to tiny physical or chemical environmental changes. This property makes them very useful for a wide range of applications: employable for experimental studies as molecular switches or for theoretical studies investigating the M-L bonds. In both cases, these studies aim to develop strategies of predictably tuning them.
Chapter One. An introduction to the SCO phenomenon: from gradual to cooperative SCO; various methods of monitoring the SCO transition. A summary of some literature examples of SCO-active systems is given. An overview of the published achievements in predicting the SCO phenomenon, including an introduction to the computational models deployed across the years. The EDA-NOCV model, employed in this field for the first time in this PhD thesis, is introduced. Finally, the aims of this study are presented.
Chapter Two. The synthesis and characterisation of four new non-symmetrical ligands, 3-(2-(5-Z-pyridyl))-4-tolyl-5-phenyl-1,2,4-triazole (LpytZ, Z = CF3, Br, F, Me), and the corresponding [FeII(LpytZ)2(NCBH3)2] complexes are presented. All four of these new complexes are SCO-active in the solid state and in CDCl3 solution, but T1/2 tuning by the meta-Z substituents was very modest. Three literature families were also tested, successfully extending the generality of using the 15N NMR chemical shift δNA of the coordinated nitrogen atom of the free ligand as measure of the T1/2 in the resulting Fe(II) complex.
Chapter Three. Theoretical study of a family of five iron(II) SCO-active [Fe(Lazine)2(NCBH3)2] (Lazine = 3-(2-azinyl)-4-tolyl-5-phenyl-1,2,4-triazole) and of the related five LS [Fe(Lazine)3(BF4)2]. The EDA-NOCV model was applied to molecular fragments to provide quantitative assessment of the σ- and π-bonding. A new corrected [Mn+ + L6] fragmentation was implemented which promises to enable a general approach suitable for any ML6 system. Finally, the σ- and π-bonding character is strongly correlated with the experimental T1/2 of the SCO-active [Fe(Lazine)2(NCBH3)2] complexes.
Chapter Four. Theoretical study of the M-L bond in a family of sixteen SCO-active differently para-X substituted [Fe(bppX)2]2+ complexes (bppX is 2,6-di(pyrazol-1-yl)-4-X-pyridine). Results of the EDA-NOCV revealed the σ-strength of the bppX ligand is correlated with σp+(X), δNA(bppX), experimental T1/2([Fe(bppX)2]2+) and calculated AILFT ΔO([Fe(bppX)2]2+). Results are explained at the molecular level by investigating the orbital population of the valence orbitals of the coordinating nitrogen involved in the aromatic π-system (pπ) and in the Fe-N bond (sp2(Fe)). From the observed correlations, the unknown σp+ parameter for two substituents (X = SOMe, SO2Me) is predicted.
Chapter Five. First theoretical study on [CoII(dpzca)2] SCO in the solid state, aiming to establish a computational protocol able to predict experimental T1/2 in pressure-activated SCO. The first part of the study validated a DFT protocol at p = 1 bar. The protocol was then extended and trialled up to 4300 bar. Results revealed good reproduction of the experimental results up to 2100 bar; but beyond this pressure, the theoretical and experimental findings diverge. Theoretical data suggest a possible phase change for the crystalline structure of HS [CoII(dpzca)2] at higher pressures than 2100 bar; this would explain why the implemented computational protocol lost validity
Investigating how pharmacists fit into the primary care non-medical prescribing landscape in New Zealand
Background
Increasing demand for health services and resource constraints have affected access to prescribing services in primary care. Some countries, including New Zealand (NZ), have introduced non-medical prescribing (NMP) to facilitate timely access to medicines. This shift in roles utilises the skills of health professionals including pharmacists to improve patients’ access to prescribing services. NMP in NZ is a relatively new health service, and little is known about the uptake, utilisation and perceptions of this service from both the public and pharmacists.
Aim
To investigate non-medical prescribing in New Zealand, and how pharmacists fit into this prescribing landscape in primary care.
Method
This thesis was conducted in five stages:
1. A literature review to establish an overview of NMP research conducted in NZ, and to identify knowledge gaps.
2. A review of data from a variety of NZ sources (NZ legislation, information from professional and regulatory organizations, policy documents, information from education providers, and grey literature) to provide an updated overview of NMP in NZ.
3. A pharmacoepidemiology study, utilising the NZ National healthcare collections to identify NMP trends in NZ primary care.
4. A discrete choice experiment to determine community pharmacists’ preferences for providing prescribing services in primary care in NZ.
5. A discrete choice experiment to determine the NZ publics’ preferences for utilising pharmacist prescribing services in primary care in NZ.
Main findings
1. There is a paucity of NZ research regarding non-medical prescribing. Little is known in NZ about the current state of NMP and how this service is being utilised. NZ research has yet to explore the place of pharmacist prescribers within primary care.
2. There is variation in the regulation, educational programmes and prescribing competencies used by the different prescribing health professionals involved in NMP in NZ.
3. NMP is not widely utilised in NZ, and nurse prescribers are the major NMP providers in primary care. Pharmacist prescribers are not well utilised and have the potential to contribute more to the NMP service in NZ.
4. NZ community pharmacists are willing to provide prescribing services in primary care in NZ using a variety of autonomous prescribing models in community pharmacies.
5. The NZ public are willing to use various models of pharmacist prescriber services in primary care if they are accessible when required, are open for longer hours, and cost less than a GP consultation.
Conclusion
Compared to the other countries, NMP in NZ is inconsistently implemented and underutilised. An overarching NMP policy should be developed to enable consistency in the various aspects of NMP. The DCEs signalled that NZ community pharmacists see themselves as part of the prescribing team, and that the NZ public are willing to utilise pharmacist prescribing services in primary care. As demand for healthcare in NZ increases, pharmacists have the potential to be part of the solution within the NMP framework in primary care. Policy makers and funders have the opportunity to utilise the outputs of this thesis to evolve the traditional role of pharmacists—to develop pharmacist prescribing services in NZ that enable equitable and timely access to prescribing for our communities
Systemic, but not local, treatment with Epothilone D improves motor skills and axonal regrowth after focal stroke in adult male mice
A stroke or cerebrovascular accident is one of the leading causes of death worldwide. Ischemic stroke, the most common form, is caused by a blockage in blood supply to the brain. It triggers a cascade of pathological events including inflammation, excitotoxicity and release of free radicals that lead to cell death. To date, drug therapies have attempted to target the loss of nerve cells. These therapies are collectively known as neuroprotectants. However, these therapies have failed to translate into the clinic. The only FDA-approved treatments for acute stroke are either thrombolytic agents such as alteplase and tenecteplase that have a therapeutic window of 4.5-6 h, or endovascular stent clot retrieval devices that can be used within 24 h. While these work well, they are only useful in approximately 15% of all stroke cases, which is why there is a compelling need to find new stroke treatments.
Recently, tumour suppression drugs have proven their ability in promoting microtubule (MT) equilibrium and growth cone development. In preclinical studies, the cancer treatment medications taxol and epothilones showed a capacity to stabilise microtubules (MTs). Epothilones have more advantages than taxol, such as the ability to cross the blood-brain barrier and induce less tissue toxicity. Epothilones represent a potential pharmacological treatment to modulate functional recovery outcomes after a stroke. Although the pharmacokinetics and pharmacodynamics of epothilone and taxol are available, more data needs to be collected to clarify their therapeutic potential. It is important to accurately test whether isotypes of these drug families can reduce drug-related side-effects, and to find the most appropriate pharmaceutical preparation for axonal growth and synaptic rewiring for functional recovery. To date, there has not been any trial to use a MT stabilizing agent in an animal stroke model. This project’s general aim is to test the effect of systemic and local administration of epothilone D on functional recovery and axonal growth in a mouse stroke model. The D isotype was investigated because it is a more potent microtubule stabilizer than other epothilone isotypes.
In this project adult male mice were randomly distributed among 6 groups (n=7 per group). Stroke was induced by photothrombosis in the treatment groups, while sham animals received the same procedure without a photothrombosis reaction. Epothilone D or vehicle was administered either as weekly 1.5 mg/kg intraperitoneal injections for 3 weeks or locally into the stroke cavity in the form of a hyaluronan/ heparin gel (5 nM). Animals were tested on grid walking and cylinder tasks for 7 weeks before euthanasia. Brains were collected for histological assessment. It was evident that epothilone D administered systemically significantly reduced the number of forelimb foot faults contralateral to the stroke injury side from 6 weeks post-stroke in a gridwalking task compared to mice receiving vehicle instead of epothilone D (P<0.05). Furthermore, axonal sprouting in the motor and premotor cortexes (assessed using neuroanatomical labelling following injection of the tract tracing dye biotinylated dextran amine, BDA) was improved in systemic epothilone D-treated stroke-affected mice in comparison to vehicle-treated stroke-affected animals (P=0.001). However, animals which received local infusion of epothilone D in the stroke cavity failed to show signs of improved behavioural outcomes or a significant change at the level of axonal sprouting. These results are promising regarding the potential use of epothilone D and other MT stabilizing drugs in stroke recovery, and they warrant further optimization to refine the delivery method and improve the outcomes
Food Sources of Energy by Socioeconomic Status in New Zealand Adolescents
The food environment and a person’s socioeconomic status are known to influence a person’s access to food and food choices. Socioeconomic status has been found to impact food sources of energy amongst adults and children; however limited research has been conducted investigating the relationship in adolescents (15-18 years old). The last New Zealand Adult Nutrition Survey was conducted over 10 years ago, and food patterns are thought to have changed since. The aim of the current study is to investigate the relationship between area-based socioeconomic status and food group consumption in adolescents, the type and amount of food they consume, and provide updated data on food sources of energy for adolescents living in New Zealand
Vitamin B12 Intakes and Contributing Food Groups of Adolescent Males in New Zealand
Background: Vitamin B12 is an essential co-factor in the one-carbon pathway, with inadequate intake eventually leading to impaired B12 function characterized by megaloblastic anaemia and neurological dysfunction. Adolescent males may be at risk of vitamin B12 deficiency due to increased requirements secondary to growth and poor diet quality. Since the last nationally representative population survey of vitamin B12 intake in 2008/09, there has been a shift across the OECD towards a more plant-based dietary pattern, potentially decreasing the consumption of dietary B12 inherent to flesh foods and dairy products. Ultimately, the current vitamin B12 intake of adolescent New Zealand males is unknown, emphasizing the need for further research in this area.
Objective: To assess the usual intake and adequacy of dietary vitamin B12 among adolescent males in New Zealand and determine the major food group contributors of vitamin B12 intake.
Design: The present study was part of a larger multi-centre cross-sectional survey of 135 adolescent males aged 15-17 years across New Zealand (Survey of Nutrition, Dietary Assessment and Lifestyles, SuNDiAL). For the purpose of the thesis, usual intakes of vitamin B12 were assessed. Participants were recruited from six secondary schools between February and March 2020. Socio-demographics, dietary habits, supplement use, attitudes and food choice motivation were assessed via an online questionnaire. Anthropometric measurements of height and weight were also collected and used to determine BMI z- score, with classification of participants as normal, overweight and obese. Dietary energy and vitamin B12 intakes were estimated using two 24-hour recalls, adjusted to establish “usual intake” using the Multiple Source Method (MSM), adequacy was determined by comparing usual intake to the estimated average requirement (EAR). The percent contribution of vitamin B12 intake from 33 major food groups were determined and ranked.
Results: Of 135 participants who completed enrolment into the study, 102 completed one 24- hr dietary recall and 72 completed the second dietary recall. The usual median (IQR) intake of vitamin B12 was 4.2 (3.9, 4.5) μg/day, with 10% of participants not achieving recommended intakes. The usual median (IQR) vitamin B12 intake appeared higher among older participants (4.6 (2.2) μg/day) and those classified as overweight (4.5 (1.9) μg/day) compared to their respective counterparts. Notably, the greatest prevalence of inadequate intake appeared in participants from the most deprived neighbourhoods (NZdepIndex 8-10), with a prevalence of inadequacy of 25%. Milk was widely consumed by most participants (75%) and as such, was ranked the largest contributor to vitamin B12 intake (21%), followed by poultry (10%), beef and veal (9.5%), fish and seafood (7.6%) and lastly, bread-based dishes (6.7%). Supplement intake was reported by 30% (37 of 122) of participants who completed the dietary habits survey – of which, 35% (13 of 37) reported consuming a B12-containing multivitamin at least once weekly. No single vitamin B12 supplemental intake was reported.
Conclusion: Despite world-wide trends toward consuming a diet rich in plant-based foods and fewer animal source foods, adolescent males in the present study had a relatively low risk of vitamin B12 deficiency, however, those from lower socio- economic areas were at moderate risk for suboptimal intakes. Further research in a more representative population of adolescent males is required to confirm the at-risk subgroups identified herein
NZDep2018 analysis of census 2018 variables - DHB14: Capital and Coast
For further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - DHB16: Nelson Marlborough
For further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - TA039: Manawatu District
For further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
Working together to improve experiences of teaching and learning Sexual and Gender Minority health at Otago Medical School
This document outlines the justification and processes for a Participatory Action Research (PAR) initiative. The project is aimed at evaluating and improving the educational climate relating to Sexual and Gender Minority (SGM) health learning at Otago Medical School (OMS) amongst medical students and academic and professional staff involved in the MB ChB program. Included is a synopsis of the background literature, the aims and proposed methods