Search

Since being introduced in the late 1990’s, enhancing recovery after surgery (ERAS) protocols have been promoted for inclusion in the care pathway for colorectal cancer patients scheduled for resection surgery (Gustaffson et al., 2012). This multimodal approach to stress management is thought to reduce the amount of surgical stress encountered; attenuating the debilitating effect surgery has on the patient and aiding subsequent recovery with a reduction in hospital length of stay reported (Lv et al., 2012). Although not currently included in ERAS, a period of pre-operative exercise training, known as PREHAB, has been proposed as a potential mechanism of improving the patient’s pre- operative fitness ahead of surgery (Carli & Zavorsky, 2005). As no research currently exists into how feasible it would be to incorporate a period of PREHAB into the current NHS colorectal cancer care pathway in the United Kingdom, this thesis aimed to address this gap in the literature as well as investigate whether participation in PREHAB would alter physical functioning and health related quality of life (HRQOL) prior to surgery and improve post-operative recovery. The impact of PREHAB on upregulating the body’s heat shock protein (Hsp) and glutathione defence systems was also explored. The purpose of the first experimental chapter was to investigate through a questionnaire-based approach whether an interest in the potential use of PREHAB existed in the Hull and East Riding area and what were the perceived benefits and barriers to participation. Over 75% of respondents indicated they would be interested in PREHAB if awaiting surgery although a lack of time (62% of respondents), cost (46%) and work responsibilities (43%) were identified as the main barriers to participation. Having established an interest existed in PREHAB, the test-retest reliability and measurement error of the five tests of physical functioning (Timed up and go [TUG], five times sit to stand [FTSTS], 5 step stair climb [SCT], handgrip dynamometry [HGD] and 6 minute walk test [6MWT]) that would be used to assess the effectiveness of the PREHAB intervention was investigated. All five tests displayed excellent test-retest reliability (all ICCs: >0.90) with the standard error of measurement and minimum detectable changes at 95% as a percentage of the mean ranging from 2.3% to 5.2% and 6.3% to 16.1% respectively. In the third experimental chapter, a randomised controlled pilot trial investigating a novel PREHAB intervention based on the joint-by-joint approach to training was conducted in colorectal cancer patients. The ineligibility of 43% (84 out of 198) of patients due to insufficient time to scheduled surgery (< 2 weeks) and subsequent poor consent rate of eligible patients (18.4%; 21 out of 114 patients) indicates implementing PREHAB into the current colorectal care pathway would be difficult. However, improvements in TUG, SCT and 6MWT performance were observed in all nine patients randomised to PREHAB (all p < 0.05), a result not replicated in the control group (improved performance at reassessment: TUG: 2 out of 9; SCT: 3 out of 9; 6MWT: 4 out of 9). This suggested that despite the limited time from recruitment to surgery (median PREHAB period: 23 [IQR: 14] days), the PREHAB programme was sufficient to improve physical functioning in these patients. There was however no significant difference in length of hospital between the two group (Control: 8 [5] days; PREHAB: 10 [7] days). In the final two experimental chapters, the effects of the PREHAB intervention on basal Hsp72 and Hsp32 expression and the glutathione defence system was explored although the low recruitment rates previously described limited the results. No changes were evident in Hsp32 or Hsp72 expression; or in total glutathione or GSH/GSSH ratio for either group during the pre-operative period. There was a potential time of day effect for monocyte Hsp72 as expression decreased in 13 out of 16 at pre-operative reassessment (p < 0.05) thus potentially masking any adaptations to have taken place. Furthermore, attempts to establish whether PREHAB altered Hsp72 inducibility were not possible due to inadequate viable samples being available. Given the limited sample size, definite conclusions were difficult to make although it was plausible the absence of change in Hsp72, Hsp32 and glutathione following PREHAB was due to insufficient stimulus being present given the often low to moderate intensity of the intervention. The findings of this thesis highlighted the issues regarding the limited time available in the pre-operative period that would need to be overcome in order to practically implement a PREHAB intervention into the current NHS colorectal cancer care pathway. Despite this, the improvements observed in physical functioning following PREHAB suggests if the intervention could be adapted to a cost-effective home-based programme it may be a viable addition to the ERAS programme.

The primary aim of this project was to both investigate injury epidemiology and create methods to potentially reduce injuries within elite ice hockey athletes. Chapter Four assessed the injury problem within ice hockey by retrospectively collecting data from two National Collegiate Athletic Association (NCAA) division III teams across a four year period investigating the prevalence, location, severity and type of injuries sustained. Findings showed that contact injuries were more prevalent (58%) than non-contact injuries (42%), with the knee (15%), shoulder (12%) and hip (13%) being the most frequently injured locations when both contact and non-contact injuries were combined. When investigating only non- contact injuries the hip complex (hip, groin and thigh) (50%) was by far the most injured location with similar frequencies, in terms of injury severity, observed. Chapter Five analysed intrinsic risk factors of the ice hockey athlete by investigating differences of hip range of motion (ROM), strength and functional tests between ice hockey athletes, soccer athletes and control participants. Results demonstrated that ice hockey athletes had significantly weaker hip adduction (p = 0.023) and flexion in sitting (p = 0.001) strength compared to soccer athletes and less external rotation strength compared to control participants (p = 0.010). Ice hockey athletes also displayed greater strength than control participants in flexion in sitting (p = 0.005). Ice hockey athletes exhibited greater ROM in abduction (p = 0.001) than control participants and greater adduction than both soccer athletes (p = 0.003) and control participants (p = 0.004). Ice hockey athletes exhibited less hip flexion in lying (p = 0.001) and external rotation (p < 0.001) when compared to control participants. Ice hockey athletes also presented with an increased number of positive flexion, abduction and external rotation (FABER) tests compared to both soccer athletes and control participants. Chapter Six investigated the effectiveness of the newly created hip screen by comparing ice hockey athletes with and without a previous non-contact hip injury and their performance during the hip screen. Findings demonstrated that athletes who had no previous hip injury had greater internal (p = 0.004) and external rotation ROM (p = 0.022) on the dominant (Dom) limb and greater flexion in sitting (p = 0.031) and internal rotation ROM (p = 0.050) on the non-dominant (Ndom) limb. Although non-significant, previously injured athletes also displayed less ROM in all hip movements compared to previously uninjured athletes. Similar trends were found in strength measures with previously uninjured athletes showing significantly stronger abduction (p = 0.012) on the Dom limb and flexion in lying on both the Dom (p = 0.008) and Ndom limb (p < 0.001). Previously injured athletes displayed more positive FABER (Dom; 13% vs. 0%, Ndom; 13% vs. 5%), Trendelenburg (Dom; 75% vs. 58%, Ndom; 50% vs. 5%) and Ober’s (Dom; 13% vs. 5%, Ndom; 75% vs. 68%) tests with higher scores on the overall screen than uninjured athletes. Chapter Seven investigated the intra and inter-tester reliability of the hip screen finding that intra-class correlation coefficients (ICC) of intra-tester reliability of the ROM (0.49), strength (0.80) and overall screen (0.76) was moderate to near perfect. Inter-tester reliability again showed very large ICCs for ROM (0.71), strength (0.77) and overall screen scores (0.81). The minimum criterion change (MCC) (3.78 points) was also found to be small for the screen score change needed to be viewed as clinically worthwhile. These findings demonstrate that the screening procedure developed is useful, reliable and repeatable when assessing the ice hockey athlete’s hip. Chapter Eight demonstrated that all participants regardless of group improved their ROM and strength measures following the intervention period. However, it was demonstrated that the ice hockey intervention (IHI) group saw a decrease in the amount of positive FABER tests following the intervention compared to ice hockey control (IHC) and intervention control (IC) group (IHI: pre 15 vs. post 6; IHC: pre 15 vs. post 14; IC: pre 10 vs. post 9). It was also demonstrated that the IHI group improved above the MCC value presented within Chapter Seven with regards to the overall hip injury screen score (pre 48 vs. post 52) indicating that ice hockey athletes who participated in the intervention programme may be at a decreased risk of sustaining a non-contact hip injury due to the intervention exercises targeting weaknesses highlighted in the hip injury screen. In summary, the current project achieved the stated aims by demonstrating that the hip complex was the most common location for injuries of a non-contact nature and the creation of a reliable and repeatable hip injury screen that allows clinicians to potentially highlight athletes considered as ‘at risk’. To complete the injury prevention sequence, future work would be necessary to track athletes who scored low on the hip injury screen over time either following the intervention or as a control to assess if they were more or less likely to sustain a non-contact hip injury. Future work should also continue to optimise the intervention strategy to further develop and enhance its effectiveness in the prevention of non-contact hip injuries. This could be achieved either through a longer protocol that is incorporated into routine training or individualisation of the programme and as such provide a valuable tool for clinicians and medical teams wishing to reduce the risk of ice hockey athletes sustaining a non-contact hip injury.

Endothelial microparticles (EMP) offer an insight into the state of the endothelium and are known to be elevated in diseases characterised by endothelial dysfunction (ED) (Horstman et al., 2004; Vince et al., 2009a). EMP have also been shown to increase after exercise/endothelial stress in healthy individuals (Sossdorf et al., 2011; Vince et al, 2009) but this area remains relatively novel. The purpose of the first experiment was to quantify the effects of an acute bout of strenuous exercise on the circulating levels of EMP and to assess if this effect is different after the ingestion of an extensively researched ergogenic aid (sodium bicarbonate, NaHCO3). Seven physically active and apparently healthy males volunteered to perform 10 x 15 second (s) cycle sprints after the ingestion of either 0.03 g.kg.BW−1 NaHCO3 or 0.045 g.kg.BW−1 of a placebo (sodium chloride, NaCl) in capsules. The ingestion of NaHCO3 induced a pre exercise alkalosis as evidenced by a significantly altered resting acid base status, but had no influence on levels of EMP in healthy males. As a result, the data was combined for the two experimental groups, and the exercise produced a significantly increased level of CD105+ MP (MP; microparticles) at 90 minutes (min) and 180 min when compared with resting levels (p = 0.010, p = 0.043 respectively). The observed peak value at 90 min was also significantly greater compared to immediately post exercise (p = 0.019). CD106+ MP also increased significantly to 90 min from immediately post exercise (p = 0.020) and this was still greater at 180 min compared to post exercise (p = 0.015). It was concluded that exercise of this nature was sufficient to elicit ED, although the endothelium shows signs of endothelial repair within a matter of hours (hr). Also, it appears that pre exercise alkalosis has no effect on the attenuation of EMP quantity. Additional work was completed to verify the novel finding that CD105+ MP and CD106+ MP appear markers of endothelial function (EF), and to further examine the quantification of EMP, this time in healthy females. There was also an additional blood draw in order to assess where the maximum level of endothelial stress was occurring post exercise. In the second experiment, 10 healthy females completed the identical repeated sprints protocol as the first experiment, this time without the ingestion of NaHCO3. CD105+ MP were increased 90 min post exercise compared to immediately after exercise (p = 0.042). There was again a decline in both markers from 90 min to 180 min, although this was not significant. Furthermore, with the addition of a blood draw at 45 min post exercise, it was suggested that EMP levels appear to be rising between 45 min and 90 min post exercise, speculating this is the time point of greatest endothelial damage. Finally, shear stress was suggested as a key reason behind the increase in endothelial damage as a result of exercise, as indicated by significant changes in variables such as heart rate (HR) and systolic blood pressure (SBP). The third experiment employed a longer 90 min interval cycling protocol with the purpose of quantifying EF over a greater period of time, allowing investigation into whether the markers of EF were altered in the same way as the previous two experiments. It was also an aim to further assess the possible influence of shear stress factors on ED. Fourteen healthy males completed 90 min of high intensity aerobic exercise, and there were several changes in both CD105+ MP and CD106+ MP. CD105+ MP rose significantly from rest to an observed peak at 90 min (p = 0.019). Both of these markers indicated a significant restoration of the endothelium as indicated by a fall from peak values during recovery to 180 min post exercise (CD105+ MP, p = 0.009; CD106+ MP, p = 0.022). This experiment concluded that the endothelium is greatly affected by highly intense exercise over a prolonged period of time, but is recovered fully in a time period of 3 hr. The effects of shear stress again appear to be largely influential, but future work must now be conducted in order to build on the findings from this research and examine shear stress closely during exercise and its relationship with EMP quantification. It was the aim of the next experiment to investigate two separate methods of assessing EF (EMP and EndoPAT-2000), this time in a group of sedentary, but otherwise healthy individuals, in order to monitor the changes as a result of an acute bout of moderate intensity acute exercise. There were no significant differences found in EF as a result of exercise. This was indicated by no significant changes in CD105+ MP concentrations from pre to post exercise (p = 0.84) or pre to 60 min post exercise (p = 0.612). CD106+ MP concentrations showed a decrease from resting values (2513 CD106+ MP per μl platelet free plasma; PFP) to immediately post exercise (1368 CD106+ MP per μl PFP, p = 0.09), and again at 60 min post exercise (1293 CD106+ MP per μl PFP, p = 0.073) compared to resting values. Additionally, EndoPAT scores were unaffected by exercise, with values of reactive hyperaemia index (RHI) changing from rest (2.43) to post exercise (2.57), but this was not significant (p = 0.35). Correlations were carried out in order to determine and comparisons that may have existed between EMP and EndoPAT score using RHI. Although there was a slight trend for the higher numbers of CD105+ MP to correlate with the lower scores of RHI (r = 0.327) this was not significant (p = 0.171). CD106+ MP showed no correlations with RHI (r = -0.087, p = 0.717). This chapter suggested that exercise was not strenuous enough to see any significant changes in EF, and EMP continue to appear efficient markers of EF in a population of sedentary, healthy individuals. The final experimental chapter investigated the effects of a supervised 8 week moderate intensity exercise programme on women with polycystic ovary syndrome (PCOS) and control women free from any known disease. The aim was to assess if this type of exercise could improve EF in this population, and if there was a relationship with EMP (CD105+ MP and CD106+ MP) to other factors, such as body composition and cardiorespiratory fitness. EF was improved from baseline values to post exercise programme, with CD105+ MP concentrations reducing from 2113 CD105+ MP per μl PFP to 424 CD105+ MP per μl PFP (p = 0.025). Furthermore, control women showed no significant change from pre to post exercise programme in CD105+ MP (p = 0.25), or CD106+ MP (p = 0.99). Further analysis was performed to look for any associations with the changes in EMP compared to body composition changes as a result of exercise, but no significant correlations existed. This study concluded that supervised, moderate intensity exercise independent of substantial weight loss was enough to elicit an00 improvement in EF in women with PCOS compared to healthy control women. Additionally, EMP concentrations appear to be able to effectively map changes in EF across a long period of time in diseased states, adding to the notion that EMP may account for EF. Future work must now build on these findings from this research and examine this response in a larger cohort involving PCOS women with varied phenotypes and body composition.