Do children using insulin pump therapy have improved management of type 1 diabetes compared with children who inject insulin daily?

Do children using insulin pump therapy have improved management of type 1 diabetes compared with children who inject insulin daily?

Good management of type 1 diabetes mellitus (T1DM) is highly important as there are many long-term complications of T1DM including cardiovascular disease, nerve damage and kidney disease. These complications are increased in diabetic adolescents to include impairment of cognition and brain development as well as interference with synapse formation, myelination and neuronal proliferation (Nevo-Shenker et al., 2020). As type 1 diabetes is typically diagnosed in children, establishing good habits through early education and identifying the most effective management of diabetes is vital to achieve optimal glycaemic control and avoid acute illnesses without compromising health-related quality of life (Mueller-Godeffroy, 2018).

For decades, the universal metric of diabetes management has typically been glycaemic control measured by glycated haemoglobin test (HbA1c) which measures ones average blood glucose levels over two to three months (Nusca et al, 2018). Effective diabetes management can also be quantified by measuring the amount of insulin required, changes to body mass index (BMI) and the incidence of acute complications such as ketoacidosis, hypoglycaemia and hypoglycaemia (Brorsson et al., 2015). Patients with type 1 diabetes mellitus face a life-long struggle of maintaining their average HbA1c within safe levels to avoid hyperglycaemia while simultaneously avoiding hypoglycaemia. Psychological health in relation to T1DM is also relevant, as the treatment regime can often be a significant burden to both the patient and their families which then affects their ability to effectively manage their T1DM and negatively impacts their overall health related quality of life (Kalra et al., 2018). The articles in this essay will outline changes in health outcomes, specifically management of type 1 diabetes through comparing multiple daily injections versus insulin pump therapy in adolescents.

PICO

P = PopulationChildren or adolescents with T1DM.

I = InterventionInsulin pump therapy.

C = ComparisonMultiple daily insulin injections.

O = OutcomeEvidence of improved management of T1DM measured through HbA1C levels, incidence of acute complications/illness, and health related quality of life.

Brorsson, A.L., Viklund, G., rtqvist, E. & Lindholm Olinder, A. (2015). Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes? A retrospective casecontrol study. Paediatric Diabetes, 16: 546-553. https://doi.org/10.1111/pedi.12209In this article, the authors used retrospectively collected data from a study carried out between 2005 2009 in Stockholm, Sweden. The article analyses the quantitative data collected from the study with the aim to compare the effectiveness of continuous subcutaneous insulin infusion also known as insulin pump therapy (IPT) versus multiple daily insulin injections (MDI) and explore the difference in long-term effects including HbA1c levels, insulin requirements, changes to BMI as well as the incidence of acute complications such as ketoacidosis, hypoglycaemia and hypoglycaemia. This case-control study was conducted in Sweden over 24 months through observing a group of 431 children who were aged between 1-17 years old at the start of the study. There were 216 participants starting on IPT and 215 using MDI. The patients on IPT were all educated prior to the study in relation to ketoacidosis, hypoglycaemic episodes, using the pump, and how to manage pump-related issues. There was a checklist developed to ensure quality and a specialist in paediatrics and endocrinology was responsible for calculating and correcting dosage of insulin as well as educating both parents and patients about ketoacidosis and hypoglycaemic events. The study was conducted over 24 months where all participants were routinely checked every three months by a diabetic nurse or physician who monitored their HbA1c levels, weight and height. Insulin usage was recorded at these 3-monthly visits and with those using IPT, the usage was recorded on their pumps and for those using multiple daily injections the usage was patient reported. The results of the study show that while overall there was a reduction in HbA1c levels for participants using IPT, this was by no means conclusive and was not sustained over the 24 months. At the 6-month stage all of the participants using IPT saw a decrease in HbA1c levels which was sustained after 12 months for the males but not for the females. The study concluded that while the IPT group had improved HbA1c levels, reduced events of severe hypoglycaemia and less insulin required; there was no notable difference in BMI and the IPT group had more incidents of ketoacidosis than the MDI group. The quality of this quantitative study was strengthened by the population of 432 which is considered an acceptable number (Martnez-Mesa et al., 2014) and is impressive considering the specificity of the requirements to participate. The fact that both groups had the exact same HbA1c baseline of 68 is also beneficial in supporting analysis of any differences in this metric. There are some limitations with this study including the fact that only the IPT group were given the pre-study standardisation education which could be a significant factor in outcomes. Another factor that could impair the studys results are the insulin requirements. Considering the IPT group was recorded through their insulin pump, this number could be much more reliable than patient reported numbers from the MDI group.

The results of this study largely mirror results of previous studies indicating improved HbA1c levels however this study differed in that it showed an increase in incidence of ketoacidosis in the IPT group. While this study showed some data supporting the premise that IPT improves glycaemic control through reducing HbA1c levels in children, the evidence also shows a lack maintenance of this reduction over time and there must be more comprehensive research to confirm the clinical benefits of IPT in children.

Mueller-Godeffroy, E., Vonthein, R., Ludwig-Seibold, C., Heidtmann, B., Boettcher, C., Kramer, M., Hessler, N., Hilgard, D., Lilienthal, E., Ziegler, A., Wagner, V. M., & German Working Group for Pediatric Pump Therapy. (2018). Psychosocial benefits of insulin pump therapy in children with diabetes type 1 and their families: The pumpkin multicenter randomized controlled trial. Paediatric Diabetes, 19(8), 14711480. https://doi.org/10.1111/pedi.12777There is a burgeoning popularity of insulin pump therapy (IPT) use among paediatric patients and the authors of this study theorise that metabolic evidence alone does not necessarily explain this uptake in IPT. This study was a randomised controlled trial conducted between 2011 2014 in Germany involving multiple locations and health institutions. The population of this trial initially included 211 adolescents aged between 6-16 years old who had been diagnosed with T1DM for at least 6 months and were already being treated with MDI of insulin. This trial is predominantly a qualitative study collecting data from the patient reported outcomes and caregiver reported outcomes. The aim of this trial was to seek to identify if there are psychosocial benefits of IPT and if they contribute to improved diabetes management and better health outcomes.

The trial was conducted by using a questionnaire with the primary outcomes of rating the patients own diabetes specific health-related quality of life (DHRQOL) in which higher scores indicating improved DHRQOL. The participants were interviewed prior to the commencement of IPT to establish a baseline of DHRQOL and again in a 6 month follow up. Their caregivers, who were often their parents were also surveyed using an intensity scale in which measured the burden of diabetes on the caregiver. There were also secondary outcomes in the study including measuring caregiver stress, fear of hypoglycaemia, family conflict, treatment satisfaction and quantitative data such as HbA1c levels.

The results on the group overall indicated an improvement of DHRQOL on average with participants aged between 8-11 years old having the most statistical significance and participants aged between 12-16 having no difference in outcomes. The other primary outcome being burden of diabetes on caregivers was reported to be significantly lower than the MDI group. The secondary outcomes varied with no reported difference to family conflict but had improved treatment satisfaction, reduced caregiver stress and less fear of hypoglycaemia. There was minimal improvement to glycaemic control as the HbA1c levels recorded only changed slightly however the results of this trial do indicate that there are several psychosocial benefits to IPT and these improvements exist in both the patients and caregivers experiences. This study is regarded as the largest of its kind and is unique in assessing the data of DHRQOL in paediatric patients. The study was strengthened by its size and participation of 18 diabetic specialist centres. The weaknesses include the lack of participants under 8 years old resulting in no comparison in that age bracket and the follow-up after 6 months only is also quite prohibitive and future studies may benefit from a longer timeframe. There is a major shift in healthcare to focus on person-centred, holistic healthcare that includes all aspects of a persons life when measuring improved health outcomes. This research provides evidence beyond physiological clinical data to include the patient and their families own experiences and improvement to psychosocial metrics which contribute to overall health and wellbeing.

de Bock, Gunn, A. J., Holt, J.-A., Derraik, J. G. B., Reed, P., Cutfield, W., Mouat, F., Hofman, P., & Jefferies, C. (2012). Impact of insulin pumps on glycaemic control in a pump-nave paediatric regional population. Journal of Paediatrics and Child Health, 48(3), 247252. https://doi.org/10.1111/j.1440-1754.2011.02245.xThis is a retrospective study analysing data obtained from a diabetes database in Auckland, New Zealand. The study used a quantitative approach to examine the impacts of IPT in children clinically. The aim of the research was to identify additional knowledge to the established research which suggests that IPT only moderately improves glycaemic control and reduces hypoglycaemia.

The research was conducted using a population of 621 children and adolescents in New Zealand who all attended the diabetes paediatric service in Auckland between 2002 and 2008. These patients were all assessed every 3 months at the service and the data recorded included HbA1c levels, self-reported frequency of blood glucose self-monitoring, daily insulin dosage, incidence of hypoglycaemia and diabetic ketoacidosis, and BMI. This study matched 75 patients using IPT with 546 patients on MDI using several metrics including age, diagnosis, ethnicity and gender.

The results of this research indicate a modest improvement of Hb1Ac levels in the IPT group as well as a reduction in risk of hypoglycaemia. While these results are not new and correlate with previous research, this study has shown a maintenance of these improvements for up to 3 years.

The IPT group in this study were mostly of European background with less societal deprivation, were younger at diagnosis and started IPT with better glycaemic control than the MDI group, all of which could affect results of the analysis. Retrospective studies such as this often have limitations as they are designedto analyse data which already exists, which then results in biases (Talari & Goyal, 2020). There are also some benefits as these studies can be quicker and cheaper to organise than other clinical trials and there is no participation bias.

This study is most beneficial to clinical practice as the data supports IPT as a safe form of treatment, reducing incidence of hypoglycaemia while noting improved rates of glycaemic control over an extended period of time.

Rosner, & Roman-Urrestarazu, A. (2018). Health-related quality of life in paediatric patients with Type 1 diabetes mellitus using insulin infusion systems. A systematic review and meta-analysis. PloS One, 14(6), e0217655e0217655. https://doi.org/10.1371/journal.pone.0217655This article is a systemic literature review in conjunction with meta-analysis of both quantitative and qualitative data collected from 15 articles using extensive inclusion and exclusion criteria. The authors chose to compare continuous subcutaneous insulin infusion also known as IPT with MDI therapy with the aim to identify which treatment regime is a more effective in relation to improving quality of life (QOL). Secondary outcomes of this review also assessed glycaemic control and incidence of adverse events and discussed front-line use of IPT and its implications to diabetic adolescents. The population of this research was both male and female children or adolescents diagnosed with T1DM aged between 6 months and 19 years and all the articles reviewed had Hb1Ac levels and quality of life as measurable outcomes.

The research collected data from the 15 articles which represented clinical trials, randomised controlled trials, cross sectional studies and a prospective observational study. There were many types of assessment tools such as questionnaires used throughout the different articles to measure QOL and where an assessment tool was absent, this study used a Mann-Whitney U test to locate the relationship between adverse events and the treatment groups with the hypothesis that less adverse events determined an improved QOL. The Mann-Whitney U test is a research tool designed to determine statistical differences that are significant between two groups (MacFarland & Yates, 2016) and in this study was used to calculate a standardised mean difference between groups. This qualitative data was then compiled along with quantitative data collected through measuring Hb1Ac levels and incidence of adverse events to provide baseline data and consequently follow up data to measure differences between groups.

The results provided slightly improved outcomes for patients undergoing IPT in all metrics including QOL, Hb1Ac levels and reduction in adverse events. These results are consistent with research from previous literature and although they address the aim of the study there is still a lot of research required to investigate the full impact of IPT on children with T1DM.

Limitations from this research are numerous and include the ambiguity of the metrics used to evaluate QOL. There were differences in the articles used including study size, location, primary source data, ages and study design. Additionally, the review was limited by differences in reporting, publication bias, and accessibility of studies as only three literature databases were used. The sheer size of the project increases the parameter of the review hugely, but this cannot be seen as entirely positive considering the lack of continuity within the characteristics of this review.

The impact of this research to clinical practice would be minimal. The data summarises many studies with mostly similar outcomes however a larger scale more focused singular approach would allow the data to be used with confidence in a clinical setting.

Literature evaluation

The articles in this bibliography are varied and collect both qualitative and quantitative data through retrospective studies, a randomly controlled trial and a systemic literature review. These are all valuable types of resources in research but have different purposes and outcomes which should be considered when researching a topic. In retrospective studies, the outcome is already available with data usually collected from existing medical records or from what the patient can recall. While these studies are cheap and quick to establish, they have the potential to include more bias and depend solely on the information that is already entered in the databases (Talari & Goyal, 2020). Randomly controlled trials in health care are studies that measure the effectiveness of a new intervention. The random nature of a trial reduces bias with a carefully selected population who through concealment do not know what group they are allocated to in the study. While this type of research can be expensive it is considered the gold standard for effective, accurate research (Hariton & Locascio, 2018). Xiao & Watson (2019) describe a systemic literature review as an essential feature of academic research which summarises, analyses and synthesises existing related literature to explore gaps and develop new theories.

In conclusion, the literature in this bibliography largely supports the research question and provides evidence that insulin pump therapy does improve effective management of diabetes in children. While there is not a significant difference in outcomes for each metric individually, the combination of improved Hb1Ac levels, reduced incidence of acute complications and improved quality of life show the potential for this intervention so improve health outcomes in type 1 diabetic children.

References

*Removed from exemplar. The student listed 11 references.

Research question

In adult combustible cigarette smokers, do nicotine electronic cigarettes compared to nicotine replacement therapy increase success rates of smoking cessation.

Introduction

Smoking is a leading modifiable risk factor for death and disease, responsible for 13% of all deaths and 8.6% of disease burden in Australia (Australian Bureau of Statistics [ABS], 2022). Combustible cigarettes contain nicotine and burn tobacco, exposing the smoker to thousands of harmful chemicals. They are highly addictive, and many smokers find quitting difficult, making smoking cessation a public health priority (Department of Health, 2019). One smoking cessation method is the use of nicotine replacement therapy (NRT) which delivers nicotine via patches, gum, lozenges, sprays, or inhalers. Another method is the use of nicotine electronic cigarettes (ECs), in which the user inhales nicotine as a vapour. ECs are increasing in popularity with 9.3% of Australian adults having used ECs (ABS, 2022). ECs are minimally regulated, however since October 2021, ECs containing nicotine are only available in Australia via prescription (Therapeutic Goods Administration, 2021). An annotated bibliography of four relevant research articles will be followed by an evaluation of this evidence on the effectiveness of nicotine ECs compared to NRT for smoking cessation.

Annotated bibliography

Bullen, C. D., Howe, C. P., Laugesen, M. M., McRobbie, H. M., Parag, V. M., Williman, J. P., & Walker, N. P. (2013). Electronic cigarettes for smoking cessation: a randomised controlled trial. The Lancet (British edition), 382(9905), 1629-1637. https://doi.org/10.1016/S0140-6736(13)61842-5

Bullen et al. used a quantitative research method to compare nicotine ECs, nicotine patches, and placebo ECs on continuous abstinence from combustible smoking. The authors argue that while there is a rapid increase in EC sales, there is a lack of reliable evidence to support their use in smoking cessation programs. This New Zealand pragmatic randomised controlled trial (RCT) had 657 eligible participants willing to quit, with 289 randomised to nicotine ECs, 295 to nicotine patches and 73 to nicotine-free ECs. Baseline characteristics were similar across all groups. Those in both EC groups were blinded to whether they received nicotine EC or nicotine-free EC. It was not possible to blind participants to EC or NRT given their method of delivery. All participants were given access to behavioural support with Quitline. The 144 participants who were lost to follow-up or discontinued were assumed to have continued smoking. At 6 months, continuous abstinence from combustible cigarette smoking was verified biochemically.

The results were not statistically significant, with 7.3% in the nicotine EC group, 5.8% in the nicotine patches group and 4.1% in the placebo EC group remaining abstinent from combustible cigarette smoking. The authors noted that continuous abstinence at 1 month was significantly higher at 23.2% in the nicotine EC group and 15.9% in the NRT group, suggesting relapse rates are high. Despite this, the authors argue that there is still the potential for improved health outcomes, as 57% in the nicotine EC group had decreased the number of combustible cigarettes per day by at least 50%. This may be due to the potential for ECs to mimic the sensorimotor aspects of smoking; however, this data appears to be relevant for those who are motivated to quit and may not be generalised to the entire combustible cigarette smoking population.

The strengths of this study include its pragmatic design pertinent to real-world effectiveness. Block and stratified randomisation to ensure even distribution among groups was evident. Both inclusion and exclusion criteria were clearly stated. There are, however, several limitations present. While a robust trial design was used to attempt to mitigate bias, there are some concerns with the overall risk of bias for this study. One author had previously received funding from a manufacturer of ECs. There is also evidence of attrition bias as the number of lost to follow-up or discontinued participants was significantly higher in the NRT group, with the authors postulating that some participants who were randomised to NRT initially joined the trial to try ECs. The authors also relied on self-reported abstinence with no evidence to suggest adherence to study protocol. It is evident that further research with larger, multi-centre trials with homogeneity of trial products is required.

Chan, G. C. K., Stjepanovic, D., Lim, C., Sun, T., Shanmuga Anandan, A., Connor, J. P., Gartner, C., Hall, W. D., & Leung, J. (2021). A systematic review of randomized controlled trials and network meta-analysis of e-cigarettes for smoking cessation. Addictive Behaviors, 119, 106912. https://doi.org/10.1016/j.addbeh.2021.106912

Chan et al. used a quantitative study method to examine the effectiveness of ECs on smoking cessation compared to NRTs, placebo, or usual care. The authors argue that the majority of evidence examining the effectiveness of ECs are from observational cohort and cross-sectional studies that have a moderate or high risk of bias. They undertook a systematic review and network meta-analysis of RCTs, which involved a direct comparison of nicotine ECs with NRT, and an indirect comparison of nicotine ECs with nicotine-free control, and indirect comparison of NRT with nicotine-free control.

Meeting the eligibility criteria were 16 trials with a total of 11,754 participants. The aim of this method was to expand the available data to assess the effect that ECs have on smoking cessation. The pooled results of this network meta-analysis showed that nicotine ECs were more effective than both NRT and nicotine-free control. The authors claimed that one potential reason for this is that ECs can not only provide a nicotine substitute for combustible cigarette smoking, but also a behavioural one.

The strengths of this review include the restricted focus on only RCTs with greater than 6 months of follow-up. The pooled data from indirect comparisons between the two treatments allowed for a much greater sample size from which to gather data. There are, however, several limitations. Many of the EC trials had a moderate or high risk of bias, and four of the included trials had a sample size of fewer than 100 participants, rendering the results of those trials inconclusive. The authors caution that there is moderate heterogeneity amongst the trials used in this meta-analysis, which may be due to the different models of ECs and NRT products used. It is therefore difficult to measure whether this impacted on the results. Follow-up duration of the included studies varied, and the nicotine-free controls differed considerably, with some studies comparing nicotine-free ECs and others only phone consultation. Chan et al. also highlight a major issue with the carbon monoxide biomarker test in that it has a very short half-life, so it may only detect combustible cigarette smoking that has occurred within the previous 2 days. The applicability to long-term smoking cessation is therefore questionable.

Hajek, P., Phillips-Waller, A., Przulj, D., Pesola, F., Myers Smith, K., Bisal, N., Li, J., Parrott, S., Sasieni, P., Dawkins, L., Ross, L., Goniewicz, M., Wu, Q., & McRobbie, H. J. (2019). A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. New England Journal of Medicine, 380(7), 629-637. https://doi.org/10.1056/NEJMoa1808779

The multi-centre pragmatic randomised controlled trial by Hajek et al. utilised a quantitative method to examine the effectiveness of ECs compared with NRT in smoking cessation. The authors reason that there is limited evidence available comparing the two treatments. A reasonable sample size of 886 participants attending the U.K. National Health Service stop-smoking services were randomly assigned to EC or NRT, with even distribution across the two therapy groups. The 439 participants assigned to EC were provided with a starter pack with product education, and if required to purchase further e-liquid replacements. The 447 participants assigned to NRT were informed on the range of NRT products available and provided with 3 months of NRT, selecting their preferred products with combination use encouraged. Both groups were provided with behavioural support for at least four weeks. Hajek et al. concluded with statistical significance (P<0.001) that ECs were more effective (18%) for smoking cessation than NRT (9.9%).

The strengths of this study include the restriction of participation to those who had no strong preference between the two treatment arms, limiting potential bias. Furthermore, while participants were not blinded due to therapy types, data analysts were, and bias is considered low given the concealed and random allocation to each treatment arm. Follow-up was at one year, suggesting the potential for long-term combustible cigarette abstinence. With its robust study design, it is one of a few studies that directly compares ECs to NRT, providing a valuable contribution to the evidence base supporting the use of ECs in smoking cessation treatment. There are, however, several limitations. Participants were dependent smokers who had a desire to quit, and they were also provided with behavioural support, so data may not be generalised outside of the UK National Health Service. Data relied on self-reporting, and although chemically tested, the method used only detects smoking in the previous 24-48hours, so there is potential for false negative results. The starter kits that EC participants were provided with only had a small supply of e-liquid, and they were advised to purchase further e-liquids themselves. This indicates that the strength of the e-liquids amongst participants were diverse, and the type of EC models used differed. Overall, this study is an important contribution to the growing body of research supporting the use of ECs, however more research through large multi-centre RCTs addressing the above limitations is required to corroborate these results.

Hartmann-Boyce, J., McRobbie, H., Butler, A. R., Lindson, N., Bullen, C., Begh, R., Theodoulou, A., Notley, C., Rigotti, N. A., Turner, T., Fanshawe, T. R., & Hajek, P. (2021). Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev, 9, CD010216. https://doi.org/10.1002/14651858.CD010216.pub6

Hartmann-Boyce et al. used a quantitative method to investigate the safety and effectiveness of nicotine ECs for combustible cigarette smokers in smoking cessation. The authors claim that the rationale behind the lack of promotion of ECs as a quit smoking aid is due to insufficient evidence on the safety and effectiveness of these devices. This Cochrane systematic review looked at a number of different comparators to ECs and included RCTs, randomised cross-over trials and uncontrolled intervention studies.

The relevance to the research question in this annotated bibliography are the four RCTs with 1924 participants that compared ECs with NRT. Only trials that undertook at least 6-months of follow-up were included in this systematic review. The results provide moderate certainty evidence that nicotine ECs are more effective for smoking cessation. Between 9-14% of nicotine EC users are likely to achieve smoking abstinence compared to 6% for NRT users. The authors also evaluated the safety of each treatment, determining that adverse events were rare and equivalent across the nicotine EC and NRT groups.

There are several strengths to this systematic review. Multiple relevant databases were searched, and monthly searches continue to be performed, making this a living systematic review that seeks out new evidence. Meta-analyses were conducted with a rigorous review process. With regards to the primary outcomes, statistical heterogeneity was low, and the included studies had an overall low risk of bias. Several limitations must also be acknowledged. Firstly, the evidence is limited by imprecision, with only a small number of trials that meet the inclusion criteria. Data collection varied, as did follow-up duration. Only smokers motivated to quit participated in the included trials, so the results may not be generalised to the wider smoking population. The authors state that several RCTs in this field are currently underway, so future updates of this living systematic review may provide more reliable evidence to guide practice.

Literature Evaluation

All of the studies included in the above annotated bibliography are unanimous that there is a paucity of reliable data available on the efficacy and safety of nicotine ECs compared to NRT in smoking cessation. All studies only included smokers who were motivated to quit, and both treatment arms were also provided with a degree of behavioural support, so it is difficult to generalise this data beyond this sample population, as it may not be applicable to the general population who do not typically have this level of support (Hajek et al., 2019).

Despite ECs showing a higher success rate over NRT, the overall effectiveness at achieving smoking abstinence is still relatively low, with the highest being that recorded by Hajek et al. (2019) at 18%. However, EC technology is rapidly changing, with current models of ECs showing improved nicotine delivery, which may result in an increase in the effectiveness of this treatment on smoking cessation (Bullen et al., 2013). The combination of both a short-acting and long-acting NRT has also been shown to improve smoking cessation success, so future studies should feature this comparator with newer models of ECs or newer ECs compared to leading pharmacotherapies to gain a clearer picture of their place in smoking cessation programs (Hartmann-Boyce et al., 2013). One such comparator is the nicotine receptor partial agonist varenicline, which is the preferred pharmacotherapy option in Australia (Royal Australian College of General Practitioners, 2021). Evidence of varenicline use in smoking cessation is considered robust and reliable (Cahill et al., 2016), so a comparison of ECs to this first-line therapy or as an adjunct is warranted.

Results show that EC use significantly reduces smoke and toxin intake compared to combustible cigarettes, so there is the potential that ECs may provide an overall improvement to public health (Hartmann-Boyce et al., 2021). In addition, Bullen et al. (2013) describe that ECs are more widely accepted by smokers than NRT and have a comparable risk of adverse events. However, as Chan et al. (2021) infer, it may be decades before the long-term impact on population health is evident. Concerns were also raised that a significant proportion of participants randomised to the nicotine EC arm continued to use ECs beyond the follow-up period, suggesting long-term use and the importance of long-term safety data (Hartmann-Boyce et al., 2021). The Australian Government are cautious about active promotion of nicotine ECs given the lack of conclusive evidence on smoking cessation, long-term harm, and the increased uptake of ECs by the younger population (Australian Institute of Health and Welfare, 2021). As Chan et al. (2021) argue, the aim should be to avoid the use of either ECs or combustible cigarettes.

Conclusion

There is a paucity of evidence comparing the efficacy of nicotine ECs to NRT. The limited evidence available shows that ECs are more effective than NRT for smoking cessation, with an equivalent degree of safety. Further research into these comparators, as well as the long-term safety of ECs, is required before these devices can be promoted as a quit smoking aid.

References

Australian Bureau of Statistics. (2022, March 21). Smoking, 2020-21 financial year. https://www.abs.gov.au/statistics/health/health-conditions-and-risks/smoking/latest-release

Australian Institute of Health and Welfare. (2021).Tobacco smoking.

https://www.aihw.gov.au/reports/australias-health/tobacco-smokingBullen, C. D., Howe, C. P., Laugesen, M. M., McRobbie, H. M., Parag, V. M., Williman, J. P., & Walker, N. P. (2013). Electronic cigarettes for smoking cessation: a randomised controlled trial. The Lancet (British edition), 382(9905), 1629-1637. https://doi.org/10.1016/S0140-6736(13)61842-5

Cahill, K., LindsonHawley, N., Thomas, K. H., Fanshawe, T. R., & Lancaster, T. (2016). Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews(5). https://doi.org/10.1002/14651858.CD006103.pub7Chan, G. C. K., Stjepanovic, D., Lim, C., Sun, T., Shanmuga Anandan, A., Connor, J. P., Gartner, C., Hall, W. D., & Leung, J. (2021). A systematic review of randomized controlled trials and network meta-analysis of e-cigarettes for smoking cessation. Addictive Behaviors, 119, 106912. https://doi.org/10.1016/j.addbeh.2021.106912Department of Health. (2019). What is smoking and tobacco? Retrieved April 11, 2022 from

https://www.health.gov.au/health-topics/smoking-and-tobacco/about-smoking-and-tobacco/what-is-smoking-and-tobacco#chemicals-in-tobacco-smoke

Hajek, P., Phillips-Waller, A., Przulj, D., Pesola, F., Myers Smith, K., Bisal, N., Li, J., Parrott, S., Sasieni, P., Dawkins, L., Ross, L., Goniewicz, M., Wu, Q., & McRobbie, H. J. (2019). A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. New England Journal of Medicine, 380(7), 629-637. https://doi.org/10.1056/NEJMoa1808779Hartmann-Boyce, J., McRobbie, H., Butler, A. R., Lindson, N., Bullen, C., Begh, R., Theodoulou, A., Notley, C., Rigotti, N. A., Turner, T., Fanshawe, T. R., & Hajek, P. (2021). Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev, 9, CD010216. https://doi.org/10.1002/14651858.CD010216.pub6Royal Australian College of General Practitioners. (2021). Supporting smoking cessation. A guide for health professionals (2nd ed.). https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-racgp-guidelines/view-all-racgp-guidelines/supporting-smoking-cessation/pharmacotherapy-for-smoking-cessationTherapeutic Goods Administration. (2021).Guidance for the use of nicotine vaping products for smoking cessation. Retrieved April 11, 2022 from https://www.tga.gov.au/node/939881

Introduction

In men over 30, do vasectomies increase the risk of prostate cancer? The answer appears to be highly controversial with several studies yielding mixed findings.

Prostate cancer is the second most common cancer diagnosed in men worldwide, and the fifth leading cause of death (Rawla, 2019). According to Bhindi et al. (2016) the aetiology of prostate cancer is unknown, but it is thought to be multifactorial involving both genetic and environmental factors. Rawla (2019) points out that an inherited genetic background has been linked to an increased risk of prostate cancer in several studies, and the risk increases after the age of 50 years. In large, prospective cohort studies, several dietary and lifestyle factors have been linked to prostate cancer risk; however, despite this research, prostate cancer has few proven modifiable risk factors (Wilson and Mucci, 2019). Other cohort studies have found links between male reproductive history and prostate cancer risk, including low ejaculation frequency, low sperm quality and low number of offspring (Rider et al., 2016; Latif et al., 2017; & Husby et al., 2020)

Several reports of an epidemiologic link between vasectomy and the incidence of prostate cancer appeared towards the late 1980s and early 1990s and this discovery sparked a debate, with several research publications supporting and disputing the association (Bhindi et al., 2016). Criticisms of previous studies that support the association centre around bias and confounding factors. Detection bias might be the reason for this positive link. Men who choose to undergo vasectomy may generally display more health-seeking behaviours and see a choose to see a urologist earlier than men who do not, reports Seikkula al., (2020). This leads to more screening and early-stage prostate cancer detection.

Vasectomy is a common, effective long-term method of birth control for men, involving a straightforward, outpatient procedure (Jacobs et al., 2016). Compared to tubal ligation, the equivalent sterilisation method for woman, it is more affordable and causes fewer complications says Jacob (2016).

For people to make knowledgeable choices about long term contraceptive methods, it is essential to understand whether vasectomy is associated with a risk of prostate cancer. Ecological studies, cohort studies, and case-control studies are the types of quantitative investigations used to identify risk factors and answer etiological questions such as these.

Annotated Bibliography

Husby, A., Wohlfahrt, J., & Melbye, M. (2020). Vasectomy and prostate cancer Risk: A 38-Year nationwide cohort study.JNCI: Journal of the National Cancer Institute(112)1, 71-77.https://doi.org/10.1093/jnci/djz099Husby et al. used a quantitative research method to evaluate the relationship between vasectomies and prostate cancer. A cohort of Danish men was established based on information retrieved from the Danish Civil Registration System and included all Danish men born between 1937 and 1996.

Of the 2, 150, 162 Danish men followed from 1977 - 2014, 139 550 men were identified as having had a vasectomy procedure for sterilisation purposes during follow-up. During the course of the study, 26 238 men developed prostate cancer (1.2 percent).

Taking into account previous cohort studies which have linked reproductive factors to prostate cancer development, Husby et al. considered potential confounding factors, including marital status, number of children fathered, number of GP visits and age at vasectomy. Only the number of children fathered changed the association noting that the more children, the stronger the association.

Overall, the authors could not claim causality due to the observational nature of the study, however it did find vasectomy to be associated with a long-term risk of prostate cancer, showing 10 years after the procedure. Vasectomised men had a 1.15 increased relative risk of prostate cancer compared to non- vasectomised men, but a 0.91 decreased relative risk of all other cancers, explained in part by a significantly lower possibility of alcohol and/or smoking-related cancers. The authors propose that vasectomised men are healthier on average than the general population.

Strengths of the study included the robust 38 yearlong study with a follow-up period of 53.4 million person-years, the largest cohort study on vasectomy and prostate cancer at the time. Using unique personal identification numbers from national registries, Husby et al. was able to obtain nationwide information to draw links on vasectomy, GP visits, socioeconomic factors, and cancer. Furthermore, to address confounding factors, individual-level socioeconomic data from Statistics Denmark on employment status, educational attainment, disposable household income, and urbanicity was obtained. Consent from the Danish research bioethics committees was not mandatory, and participants were not contacted.

Limitations to the study include no account for other reported prostate cancer risk factors, such as dietary and lifestyle factors, sexually transmitted diseases, body mass index, and family history of prostate cancer.

In conclusion, the study cannot claim causality due to the study being observational in nature; nonetheless, the findings can assist in quantifying any potential adverse effect of vasectomy because it is impossible to conduct a randomised experiment.

Siddiqui, M.M., Wilson, K.M., Epstein, M.M., Rider, J.R., Martin, N.E., Stampfer, M.J., Giovannucci, E.L., & Mucci, L.A. (2014) Vasectomy and risk of aggressive prostate cancer: a 24-year follow-up study.Journal of Clinical Oncology,32(27), p3033-3038. doi:10.1200/JCO.2013.54.8446

This quantitative study extends the follow-up, by 6 decades, of one of the largest prospective studies, the Health Professionals Follow-up Study (HPFS) cohort by Giovannucci et al. (1993). More than 6,000 patients with prostate cancer were followed to investigate a comprehensive association between vasectomy and the risk of advanced stage and lethal prostate cancer.

The HPFS comprises of a cohort of 51,529 male health professionals aged between 4075 years (at the time of initiation in 1986) living in the United States. The men received biennial questionnaires gathering information about themselves in relation to their lifestyle and health outcomes, including whether they have had a vasectomy. Medical records and pathology reports were used to detect prostate cancer diagnoses, as well has self-reports from the study participants or next of kin. Men with early stage cancer were excluded.

Results of the study revealed a small increased risk of prostate cancer (R.R. 1.10) associated with vasectomy. The relative risk for high-grade and lethal disease was higher (1.2). The association was even stronger in a smaller sub cohort of men who received PSA screening. The study reported no association with the risk of low-grade or localised cancer. Further investigations ruled out associations motivated by sex hormone levels, STIs, or cancer treatment.

A key strength of Siddiqui et al.s analysis is the vigorous representation of one of the largest cohort studies at the time with the longest follow-up (>90%) helping to build confidence in the studys outcomes. Additional strengths lie in the studys strong covariate data, and the controls put in place for strength of PSA screening as well as potential confounders such as STDs. The study only focused on the incidence of advanced and lethal prostate cancer, and incidence of prostate cancer in a highly screened subgroup, to further reduce the potential for bias due to PSA screening.

The authors acknowledge that due to the observational nature of the study the choice to undergo vasectomy was preferential, introducing possible confounding. A further limitation to the study could be grading errors as a result of changes in the grading scale over time. Lastly, there is the possibility that residual confounding could have masked the moderate association of risk of aggressive and/or fatal prostate cancer. This would be the case if men who underwent vasectomy were substantially more likely to have had prostate cancer detected earlier than those without vasectomies.

Nonetheless, the research by Suddiqui et al. supports the theory that vasectomy is linked to a small increased prostate cancer incidence, and it is doubtful these results are due to detection bias, and confounding.

Jacobs, E. J., Anderson, R. L., Stevens, V. L., Newton, C. C., Gansler, T., & Gapstur, S. M. (2016). Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34(32), p38803885. https://doi.org/10.1200/JCO.2015.66.2361

In this quantitative study, Jacobs et al. investigated the associations of vasectomy with both prostate cancer incidence and prostate cancer mortality, using the Cancer Prevention Study II (CPS-II), a prospective mortality study of approximately 1.2 million American men and women dating back to 1982. Most men in the study enrolled with their wives and were identified as spouse pairs. While the men were not asked if they had had vasectomies the womens questionnaire included questions on contraception and included partner vasectomy. Unmarried men in the CPS-II in 1982 were excluded from the study.

363,726 men were examined in the CPS-11, and 7,451 died from prostate cancer during the follow-up period from 1982 to 2012. The study also looked at the association between vasectomy and the incidence of prostate cancer in the 66,542 men using the CPS-II Nutrition Cohort, a subgroup of CPS-11. 9,133 were diagnosed with prostate cancer in the follow-up period from 1992 to 2011.

Jacobs et al. reported no association between vasectomy and prostate cancer mortality in CPS-II and similarly, the study did not find an association between vasectomy and overall prostate cancer incidence or incidence of high-stage and high-grade prostate cancer in the CPS-II Nutrition Cohort. However, a small association was found in the last five years of follow-up with greater risk of non-aggressive prostate cancer. The results of this study differed from the HPFS study which was similar in design and the authors hypothesise this might be down to chance.

Key strengths of this analysis include its large cohort and its prospective design. The CPS-II was a suitable study to investigate the association between prostate cancer risk and vasectomy due to its unusually large size.

Jacobs et al. acknowledged that the reporting of vasectomy by the participants wives might be a limitation to the results. The authors also noted that residual confounding could not be ruled out due to inaccurate self-reporting of PSA testing. A further limitation, as a result of the observational nature of the study, is the possibility of some bias and a small increase in risk of prostate cancer should not be discounted. Furthermore, data on vasectomies may have been misclassified if they occurred after study enrolment.

The studys results provide some confidence that vasectomy is not likely to increase a mans risk of prostate cancer.

Seikkula, K.A., Hirvonen, E., Rantanen, M., Pitkniemi, J., Malila, N., & Bostrm, P. J. (2020). Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort.Cancer Epidemiology, 64, p101631101631.https://doi.org/10.1016/j.canep.2019.101631This quantitative study aimed to evaluate the potential association between vasectomy and prostate cancer incidence and mortality from national registries in Finland. Seikkula et al. identified every man who had a vasectomy in the years 1987-2014, from the Finnish sterilisation registry. To obtain information on patients diagnosed with prostate cancer after their vasectomy, the personal identification of the cohort members was linked to the Finnish Cancer Registry (FCR). For calculating incidence ratios, the study followed each man from vasectomy until prostate cancer, death or 2014, and for assessing mortality, follow-up ended to death or 2014. Over the follow-up period, 413 of the 38, 124 men who had undergone vasectomy developed prostate cancer after vasectomy. 19 men in the cohort died from prostate cancer, and 1168 men died from overall mortality from other causes during the study period. The authors reported a slight increase in prostate cancer risk after a vasectomy, however, the mortality rate of vasectomised men was only 50 percent of the general male population.. In this study, the incidence of prostate cancer increased within ten years of vasectomy.

Key strengths of this study included the nationwide cohort of 38,124 Finnish men, with a follow up of nearly 430 000 person-years building trust in the outcome of the study. The cohort included every man who had undergone vasectomy after January 1st, 1987, the year when the electronic sterilisation registry commenced, and reporting of vasectomy became mandatory practice.

Limitations to the study centre around detection bias, where the authors suggest that the rise in incidence of prostate cancer in vasectomised men might be due to more active surveillance or health seeking behaviour and increased PSA screening. In Finland it is well documented that PSA screening has become more common since the late 1990s and Seikkula acknowledges that one can assume that most cancers in this study were found through higher PSA values. Secondly, the population in the cohort was still relatively young to have prostate cancer, so a lengthier follow-up time would better report the prostate cancer risk and mortality in vasectomised men. Furthermore, because the mortality of this cohort was only 50 percent of the corresponding standard male population, which the authors have suggested that the association between vasectomy and Prostate cancer is possibly due to healthier lifestyle habits of men with a history of vasectomy.

The research by Seikkula et al. builds on the growing body of research that supports the association between vasectomy and the incidence of prostate cancer.

Final evaluation and conclusion

The association between vasectomy and prostate cancer has been investigated for decades. While there is still no plausible biological mechanism by which a vasectomy should increase a mans risk of prostate cancer, these studies provide evidence to suggest it does, albeit minimally.

Three of the four studies reviewed in this paper support the theory that there is a modest association between vasectomy and prostate cancer however the authors cannot claim casualty due to the observational nature of their studies, and bias is still a possibility.

A trial that randomises men to undergo vasectomy versus no vasectomy would be the only way to tackle bias, but this would not be ethical, and a long enough follow-up period would not be feasible. Strengths of the four studies included the large, and in some cases nationwide, cohorts with long follow-up times, helping to build confidence in all of the studies outcomes.

If the relative risk (< 1.2) in the three studies has minimal clinical impact, concerns about prostate cancer risks should not dissuade men from selecting vasectomy as a contraception method. However, the risk might be clinically important depending on a mans lifetime prostate cancer risk. If his baseline risk is already elevated this would merit consideration when selecting a method of contraception.

Ultimately the decision to undergo vasectomy should be decided based on examination of all the evidence, and men should consider the benefits and potential risks.

References

Bhindi, B., Wallis, C.J.D., Nayan, M., Farrell, A., Trost, L., Hamilton, R., Kulkarni, G., Finelli, A., Felshne, N., Boorjian, S., & Karnes, R. (2017). The association between vasectomy and prostate cancer: a systematic review and meta-analysis. Journal of the American Medical Association: JAMA, 1777 (9). file:///C:/Users/maxlo/Downloads/jamainternal_bhindi_2017_oi_170055%20(1).pdfCheng, S., Yang, B., Xu, L., Zheng, Q., Ding, G., & Li, G. (2021). Vasectomy and prostate cancer risk: A meta-analysis of prospective studies.Carcinogenesis, 42(1), 3137. https://doi.org/10.1093/carcin/bgaa086Giovannucci, E., Ascherio, A., Rimm, E.B., Colditz, G.A., Stampfer, M.J., & Willett, W.C. (1993). A prospective cohort study of vasectomy and prostate cancer in US men. The Journal of the American Medical Association, 269(7), p873-7.

Husby, A., Wohlfahrt, J, & Melbye, M (2020). Vasectomy and prostate cancer Risk: A 38-Year nationwide cohort study.JNCI: Journal of the National Cancer Institute 112(1), 71-77. https://doi.org/10.1093/jnci/djz099Jacobs, E. J., Anderson, R. L., Stevens, V. L., Newton, C. C., Gansler, T., & Gapstur, S. M. (2016). Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort.Journal of clinical oncology: official journal of the American Society of Clinical Oncology,34(32), p38803885. https://doi.org/10.1200/JCO.2015.66.2361

Latif, Jensen, T. K., Mehlsen, J., Holmboe, S. A., Brinth, L., Pors, K., Skouby, S. O., Jrgensen, N., & Lindahl-Jacobsen, R. (2017). Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men with Long-Term Follow-up.American Journal of Epidemiology,186(8), 910917. https://doi.org/10.1093/aje/kwx067

Merriel, S.W.D., Funston, G. & Hamilton, W. (2018) Prostate Cancer in Primary Care.Advanced Therapy,35,p12851294. https://doi.org/10.1007/s12325-018-0766-1Mucci, L. A., Wilson, K. M., Preston, M. A., & Giovannucci, E. L. (2020). Is Vasectomy a Cause of Prostate Cancer?JNCI: Journal of the National Cancer Institute,112(1), p56. https://doi.org/10.1093/jnci/djz102Rawla, P. (2019). Epidemiology of Prostate Cancer.World Journal of Oncology, 10(2), p63-89. doi:10.14740/wjon1191

Rider, J.R., Wilson, K. M., Sinnott, J. A., Kelly, R.S., Mucci, L.A., Giovannucci, E.L. (2016). Ejaculation frequency and risk of prostate cancer: updated results with an additional decade of follow-up. European Urology, 70(6):974982. https://doi.org/10.1016/j.eururo.2016.03.027

Seikkula, K.A., Hirvonen, E., Rantanen, M., Pitkniemi, J., Malila, N., & Bostrm, P. J. (2020). Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort. Cancer Epidemiology, 64, p101631101631. https://doi.org/10.1016/j.canep.2019.101631Siddiqui, M.M., Wilson, K.M., Epstein, M.M., Rider, J.R., Martin, N.E., Stampfer, M.J., Giovannucci, E.L., & Mucci, L.A. (2014) Vasectomy and risk of aggressive prostate cancer: a 24-year follow-up study. Journal of Clinical Oncology, 32(27), p3033-3038. doi:10.1200/JCO.2013.54.8446

Wilson, K.M., Mucci, L.A. (2019). Diet and Lifestyle in Prostate Cancer. Advances in Experimental Medicine and Biology, 1210. https://doi.org/10.1007/978-3-030-32656-2_1

RESEARCH QUESTION - Are IDF recommended lifestyle modifications as effective as pharmaceutical interventions in avoiding progression to a diagnosis of T2DM for patients diagnosed as pre-diabetic?

BACKGROUND - According to the International Diabetes Federation (IDF, 2021), there are 537 million T2DM cases globally. This is predicted to rise to 784 million in 2045. Since 2001 cases have tripled; making it the worlds fastest growing, non contagious health challenge. A T2DM diagnosis has a significant impact on both individual health and life expectancy (World Health Organisation [WHO], 2016). Whilst some of the factors contributing to this surge are unmodifiable, there is also evidence that modifiable risk factors include diet, obesity and a sedentary lifestyle (IDF, 2021).

INRODUCTION - This paper contains four annotated bibliographical entries which address this topic. Broadly, each entry supports the health benefits of the IDF recommended interventions. The first selected study by Davies et al., (2016) demonstrates the benefits of community support, personal empowerment and dietary education, in avoiding disease progression. The second study by Marsden et al., (2022) demonstrates that an online approach, can provide effective and wide-reaching interventions. The third entry by the Diabetes Prevention Program Research Group (2015) focuses on the long term difference between available treatment options, disease progression and complications. In the fourth study Sun et al., (2017) addresses costs. Seeking to ensure a balance between expenditure and effectiveness, the authors inform and benefit key stakeholders to balance modifications with pharmaceutical interventions and avoid a T2DM diagnosis.

ANNOTATED BIBLIOGRAPHY

Davies, M., Gray, L. & Troughton, J. (2016). A community based primary prevention programme for type 2 diabetes integrating identification and lifestyle intervention for prevention: The Let's Prevent Diabetes cluster randomised controlled trial. Preventive Medicine. 2016 Mar; 84:48-56. DOI: 10.1016/j.ypmed.2015.12.012. PMID: 26740346.

AIM - This randomised controlled trial takes a quantitative approach to its primary aim of researching the efficacy of recommended lifestyle and dietary interventions in preventing progression to a T2DM diagnosis. Davies et al., (2016) use a community based primary diabetes prevention program. Enrolling hyperglycaemic participants, considered to be at high risk of disease progression, the authors take a collaborative, longitudinal approach to the research topic. The purpose of this study was to investigate how to effectively implement the existing preventative research in a primary health care setting for participants with an existing pre-diabetes diagnosis. This information could then inform the efficacy of targeting dietary choices and activity levels and preventing disease progression, when compared to standard pharmaceutical interventions. METHOD - A meta-analysis of 44 general medical practices were chosen at random to either implement a 6 hour structured educational program, supported by regular telephone contact and a yearly refresher course or the provision of standard pre-diabetes medical care. Participants were over the age of 18, not pregnant, hyperglycaemic and considered to be at high risk of disease progression. Data in this randomised controlled trial was gathered for a period of 3 years. The measurable outcome was disease progression, crossing the threshold from persistent hyperglycaemia to a T2DM diagnosis. RESULTS There was a total of eight hundred and eighty participants. This was comprised of 36% female, with a mean age of 64 years and 16% representing an ethnic minority. From this cohort 131 participants went on to develop T2DM during the allocated time frame and showed an insignificant reduction in the risk of disease progression in comparison to standard pharmaceutical care. EVALUATION - This study is relevant, valid, current and unlikely to be effected by bias. The strength of this study lies in the size of its cohort and its ability to address the hypothesis. It is also strengthened by its use of electronic medical records to research and activist practices to provide insight, generate new knowledge and simultaneously engage relevant stakeholders as a means of generating fundamental societal change. The allocation to treatment groups was concealed, the participants were similar at baseline and the outcome was standardised. This type of research aims to improve outcomes of pre-diabetic participants through empowering strategies and information to improve individual health. A weakness lies in its restricted scope of participation and the lack of direct, individual monitoring of participants for adherence. The study also did not account for the various socioeconomic and other demographic influences in the participants. The study ultimately concluded that incorporating education is an effective means of providing improved outcomes, reducing disease progression through a specific and low cost, preventative approach whilst simultaneously empowering the studys participants. CONCLUSION -This study has significant implications for further research and for clinical practice. The authors show that although low cost, community based diabetes prevention programs may result in modest benefits to biomedical, lifestyle and psychosocial outcomes, the reduction of the risk of a T2DM diagnosis does not reach significance. The results still illustrate the importance of diabetes prevention as participation in the program was associated with reduced levels of hyperglycemia, clinically significant weight loss and improved HbA1c results. This result supports the importance of diabetes prevention. Outcomes were assessed based on either the development of a T2DM diagnosis and / or the presence of microvascular disease, comprising neuropathy, retinopathy and nephropathy. These findings have important implications for guiding and informing future T2DM and primary care research.

Marsden, A.M., Bower, P. & Howarth, E.et al.Finishing the race a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme.Int J Behav Nutr Phys Act19,7 (2022). https://doi.org/10.1186/s12966-022-01249-5

AIM The authors primary aim is to quantify and analyse the impact of the program on participants weight and blood glucose levels. Marsden et al., (2022) examine and report upon both the physical changes and reasons that correlate with the recorded changes, measuring both weight, fasting plasma glucose and HbA1c (haemoglobin A1c) levels to monitor the status of the 36,000 participants in the 'Healthier You' program. Healthier You was an intensive, diet and exercise behavioral intervention aimed at preventing progression to T2DM carried out in the United Kingdom (UK) between 2016 and 2019. METHOD Patient level data was continuously gathered and analysed for deviations from the initial data which formed the statistical baseline. This data was then used to demonstrate the programs effectiveness and levels of engagement, with a quantitative, longitudinal, pre and post test design and a mixed method approach to the research question. RESULTS - The results were grouped into three specific areas; the uptake, the use of and the impact of the interventions. At the annual follow up, the data showed an average weight loss of between 2.8 and 3.4 kg and a reduction of between 1.4 to 1.8 mmol for HbA1c. Regular access to peer, website and telephone support was associated with considerably higher reductions in both HbA1c and weight loss. EVALUATION This study is relevant, valid, current and unlikely to be effected by bias. This study addresses the question, with its size supporting the accuracy of the resulting data. The interventions aim provided strong parameters, but it doesnt acknowledge variables such as age and employment status and the size of the cohort reduced the capacity for the direct monitoring of participants. CONCLUSION This study demonstrates that a digital approach can provide an effective and wide-reaching, population-based contribution to T2DM prevention. It focused on adherence to the recommended diet and activity guidelines and resulted in a clinically significant reduction in two of the variables; HbA1c and body weight. An outcome which supports the health benefits of the recommended diabetes prevention lifestyle modifications. This online success is however, qualified by the minimum of 16 hours of direct contact over the 13 sessions available within the programs timeframe. Revealing the specific nature of the studys additional requirements, informs future T2DM primary care research. Ultimately, showing that lifestyle interventions can significantly reduce diabetes development through a low cost, high impact, preventative approach to disease progression.

Diabetes Prevention Program Research Group (2015). Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: The Diabetes Prevention Program Outcomes Study.The Lancet. Diabetes & endocrinology,3(11), 866875. https://doi.org/10.1016/S2213-8587(15)00291-0

AIM This study takes a quantitative approach to the research and the primary aim is to compare the recommended intensive lifestyle interventions, with masked metformin and a placebo in a group of pre-diabetic participants at high risk of disease progression. The authors seek to determine whether the intensive application of the recommended lifestyle interventions results in comparable control of hyperglycaemia when compared with standard pharmaceutical care. METHOD This program was a randomised, controlled, clinical trial conducted through 27 randomly selected medical centres across the United States of of America (US). All participants were offered recommended lifestyle intervention support semi-annually, with the pharmaceutical group receiving unmasked metformin. RESULTS During the 15 year follow up period, transition to a T2DM diagnosis was reduced by 27%in the lifestyle intervention group and by 18% in the standard pharmaceutical care group, in comparison to the placebo group. These differences reduced over the studys timeframe. EVALUATION This study is relevant, valid, current and unlikely to be effected by bias. This study specifically addresses the hypothesis. It was concluded a full year before the scheduled completion date because the independent data safety monitoring board deemed the question had been fully addressed. The use of comparators and randomisation strengthens the resulting data and ensures that altered outcomes are able to more accurately be assigned to the interventions. The allocations were anonymous and all participants were treated identically, apart from the interventions pertaining to the study. There was however, a lack of very direct monitoring of the participants in order to verify stated adherence levels. CONCLUSION At the conclusion of the study the instance of microvascular complications did not vary significantly between the participants in any of the treatment groups. The recommended lifestyle intervention group had a T2DM incidence of 55%. It was 56% in the pharmaceutical group and 62% for those participants who received a placebo. This study demonstrates that both the recommended lifestyle intervention group and the standard pharmaceutical care group experienced a significant reduction in disease progression.

Sun, Y., You, W., Almeida, F., Estabrooks, P., & Davy, B. (2017). The effectiveness and cost of lifestyle interventions including nutrition education for diabetes prevention: a systematic review and meta-analysis.Journal of the Academy of Nutrition and Dietetics,117(3), 404-421.

AIM - This study takes a quantitative approach to testing both the effectiveness and the costs associated with the recommended lifestyle and dietary modifications. The authors aim to assess and quantify the results from diabetes prevention programs through a systematic review and meta-analysis. Data from between 2000 and 2015 was used to synthesise the costs, benefits and efficacy of the recommended lifestyle modifications and then compared against alternative sources. For example; face to face versus online or homemade versus dietician prepared meals. The authors then sought to test the effectiveness of lifestyle interventions. Aiming to determine which specific aspects of the programs correlate with the successful implementation of the recommended modifications and delay or avoid progression to a T2DM diagnosis. METHOD - A systematic review of the relevant literature researching the efficacy of recommended diet and lifestyle modification programs, designed to prevent disease progression for participants with persistent hyperglycaemia. The review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (PRISMA, 2021). The measurable outcome was disease progression, crossing the threshold from persistent hyperglycaemia to a T2DM diagnosis. RESULTS - Study participants were anonymously divided into either the intervention group or the control group. Health scores included data such as; Body Mass Index (BMI), waist circumference, medical and family history were compiled at both baseline and again 6 months later in order to analyse for clinical variables and assess the efficacy of the interventions. The subsequent analysis was moderated through the separate use of both intervention and control practices in order to reveal the most practical, accurate and usable data. For example; participants getting the nutritional education intervention revealed varying degrees of weight loss over the following 12 months, whereas participants in the dietician prepared intervention although revealing a relatively larger weight loss also incurred higher costs associated with the intervention. EVALUATION - This study is relevant, valid, current and unlikely to be effected by bias. The strength of this study lies in its ability to address the most practical aspect of the hypothesis and in that way guide and inform practice, provide additional insight for future research and engage the relevant stakeholders. Also, being conscious of any associated costs incurred during the implementation of the lifestyle interventions means that the nature of the data gathered for this study provides real world valid and informative data for future research in this area. An area of weakness that could be found in the study was the lack of a comparator, only using publications written in English. There was also a lack of specifics regarding costing and further to this the authors did not address the more specific socio-economic circumstances, specific preferences or special interests related to diet and nutrition. CONCLUSION - This study indicated that participation in a digital diabetes prevention program that focused on adherence to recommended diet and activity guidelines resulted in a clinically significant reduction in two of the variables; HbA1c and body weight and is a lost cost, high impact, specific and accessible element of an entire population approach to preventing those with a pre-diabetic diagnosis progressing to a T2DM diagnosis.

LITERATURE EVALUATION

A search for relevant articles was carried out through the Charles Darwin University (CDU) library database. Each of the 4 articles selected was deemed to be relevant to the research question, valid and peer reviewed, current to within a timeframe of the previous 10 years and unlikely to be effected by bias. The selected articles all declared any conflicts of interest and contained both a clearly stated methodology and specified inclusion and exclusion criteria. Each of the studies provided purposeful sampling, quantitative and explanatory outcomes and also addressed aspects of empowering and informing stakeholders, targeting hyperglycaemia and avoiding disease progression. Differences exist in areas such as the research methodology, strengths and weaknesses, the trajectory it offers for further research and its relevance for future clinical practice (Greenhalgh, 2020).

CONCLUSION

The entries in this annotated bibliography address various aspects of the research question, and present high quality evidence to identify risk factors, empower participants and inform future research in the quest to prevent disease progression. The benefits of community support, the scale of intervention made possible through an online approach, the long term health benefits and the cost effectiveness of prevention are all addressed. Through these papers, the authors have made a small but significant contribution to combatting the worlds fastest growing, non-infectious health challenge.

References

Davies, M., Gray, L. & Troughton, J. (2016). A community based primary prevention programme for type 2 diabetes integrating identification and lifestyle intervention for prevention: The Let's Prevent Diabetes cluster randomised controlled trial. Preventive Medicine. 2016 Mar; 84:48-56. DOI: 10.1016/j.ypmed.2015.12.012. PMID: 26740346.

Diabetes Prevention Program Research Group (2015). Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: The Diabetes Prevention Program Outcomes Study.The Lancet. Diabetes & endocrinology,3(11), 866875. https://doi.org/10.1016/S2213-8587(15)00291-0

Greenhalgh, T., M. (2020).Understanding research methods for evidence-based practice in health. (2nd ed.). Wiley, Australia. https://ebookcentral.proquest.com/lib/cdu/reader.action?docID=6488129

International Diabetes Federation (2021).Diabetes Atlas-10th Edition. https://diabetesatlas.org/

Marsden, A.M., Bower, P. & Howarth, E.et al.Finishing the race a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme.Int J Behav Nutr Phys Act19,7 (2022). https://doi.org/10.1186/s12966-022-01249-5

Sun, Y., You, W., Almeida, F., Estabrooks, P., & Davy, B. (2017). The effectiveness and cost of lifestyle interventions including nutrition education for diabetes prevention: a systematic review and meta-analysis.Journal of the Academy of Nutrition and Dietetics,117(3), 404-421.

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ2021;372doi:https://doi.org/10.1136/bmj.n71

World Health Organisation. Global report on diabetes. Geneva: World Health Organisation; 2016.