Modelling and predicting patient recruitment in multi-centre clinical trials

One of the main concerns in multi-centre clinical trials is how to enrol an adequate number of patients during a specific period of time. Accordingly, the sponsors are keen to minimise the recruitment time for cost effectiveness purposes. This research tended to concentrate on forecasting the patients’ accrual time for the pre-arranged number of sample size by simulating an on-going trial. The method was to model the data from the recruitment frequency domain and apply the estimations derived from the frequency domain to predict the time domain. Whereas previous papers did not concentrate on variations of recruiting over centres, this research assumed that patient arrivals followed the Poisson process and let the parameter of the process vary as a Gamma distribution. Consequently, the Poisson-gamma mixed distribution was confirmed as the promising model of the frequency domain. Then with the help of the relationship between the Poisson process and the exponential distribution, accrual time was predicted assuming that the waiting time between patients followed the Gamma-exponential distribution. As the result of the project, a trial was simulated based on the estimated values derived from completed trials. The first part of the prediction estimated the expected average number of patients per centre per month in an on-going trial. The second part, predicted the length of time (in months) to enrol specific number of patients in the simulated trial

Length-structured approach to fisheries stock assessment

Modern fishing fleets have the capacity to over-exploit fish stocks. Inaccurate assessments could overestimate the stock size and as a result Total Allowable Catches (TAC) are set too high for sustainable stock conservation. Fisheries management need robust and reliable stock assessments to ensure that the species and environmental effect of fishing is sustainable. Since the demand for ecosystem based approaches to management has increased, the needs for improved estimates of un-assessed abundance have risen. Managers simply need to know how many fish left in the see and how much to limit the fishermen to fish to have sustainable fisheries. Therefore, accurate assessment of the market as well as by-catch stocks and records of true landings and discards are critical aspects of the scientific advice to the fisheries managers to accurately set TACs. Here, we consider the marine species that are left un-assessed. That is because they cannot be assessed by the existing methods. We therefore sought to fill the key gap with this matter. This thesis has five key elements. First we reviewed the stock assessment method with the emphasis on the length-structured models. Second, we produced a population model (so called survey-landings model) to make the use of survey frequency data extracted from International Bottom Trawl Survey and total annual landed biomass from commercial reports. Third, within a twin-experiment context and sensitivity analysis the model was assessed for accuracy and robustness in variability in initial parameter values and observational noise. Forth, applying the survey-landings model the population dynamics of the North Sea haddock was assessed and the results were compared with the International Council for Exploitation of the Sea assessment. Fifth, after the model proved to be reliable it is used as an alternative for age- or catch-at-length model, the population of the North Sea grey gurnards were modelled with confidence. This model enabled un-assessed species such as grey gurnards to be modelled and assessed for the first time.Modern fishing fleets have the capacity to over-exploit fish stocks. Inaccurate assessments could overestimate the stock size and as a result Total Allowable Catches (TAC) are set too high for sustainable stock conservation. Fisheries management need robust and reliable stock assessments to ensure that the species and environmental effect of fishing is sustainable. Since the demand for ecosystem based approaches to management has increased, the needs for improved estimates of un-assessed abundance have risen. Managers simply need to know how many fish left in the see and how much to limit the fishermen to fish to have sustainable fisheries. Therefore, accurate assessment of the market as well as by-catch stocks and records of true landings and discards are critical aspects of the scientific advice to the fisheries managers to accurately set TACs. Here, we consider the marine species that are left un-assessed. That is because they cannot be assessed by the existing methods. We therefore sought to fill the key gap with this matter. This thesis has five key elements. First we reviewed the stock assessment method with the emphasis on the length-structured models. Second, we produced a population model (so called survey-landings model) to make the use of survey frequency data extracted from International Bottom Trawl Survey and total annual landed biomass from commercial reports. Third, within a twin-experiment context and sensitivity analysis the model was assessed for accuracy and robustness in variability in initial parameter values and observational noise. Forth, applying the survey-landings model the population dynamics of the North Sea haddock was assessed and the results were compared with the International Council for Exploitation of the Sea assessment. Fifth, after the model proved to be reliable it is used as an alternative for age- or catch-at-length model, the population of the North Sea grey gurnards were modelled with confidence. This model enabled un-assessed species such as grey gurnards to be modelled and assessed for the first time

Working Health Services Scotland: a four-year evaluation

Background: Working Health Service Scotland (WHSS) supports the self-employed and employees of small and medium-sized enterprises (SMEs) in Scotland with a health condition affecting their ability to work, who are either absent or at risk of becoming absent due to it. Aims: To evaluate the impact on health and work outcomes of WHSS clients over a 4-year period. Methods: Data were collected at enrolment, entry, discharge and follow-up at 3 and 6 months after discharge. Clients completed up to three validated health questionnaires at entry and discharge—EuroQol five dimensions (EQ-5D) and visual analogue scale (VAS); Hospital Anxiety and Depression Scale (HADS); and Canadian Occupational Performance Measure (COPM). Results: A total of 13463 referrals occurred in the 4-year period; 11748 (87%) were eligible and completed entry assessment and 60% of the latter completed discharge paperwork. The majority of referrals were due to musculoskeletal conditions (84%) while 12% were referred with mental health conditions. Almost a fifth (18%) of cases were absent at entry and back at work at discharge. Work days lost while in WHSS was associated with age, length of absence prior to entering WHSS, primary health condition and time in programme. All health measures showed significant improvements from entry to discharge. Improvement in general health was sustained at 3- and 6-month follow-up. Conclusions: The WHSS evaluation findings indicate that participation was associated with positive changes to health and return-to-work. The extent of the positive change in health measures and work ability can be highly important economically for employees and employers

Measuring the Success of Mathematics and Statistics Support Sessions at UWS

Following a review of the provision of mathematics and statistics support across Scottish Higher Education Institutions, academics at the University of the West of Scotland initiated weekly mathematics and statistics support sessions. These sessions were open to all students and staff across the institution, but primarily aimed at the science and engineering students with a high degree of numerate work in their study programmes. After two years of operation, previous attendees and students within key demographics were canvassed on their knowledge of, and opinion of, these support sessions. Four key points were uncovered: advertising of the existence of the sessions should be increased; the use of PhD students overseeing the sessions should be investigated; the centralisation of the sessions should be investigated; and more formal tutorial engagement should be encouraged

The effect of different types of bariatric surgery on Levothyroxine requirement in hypothyroid bariatric patients

Background Bariatric surgeries are carried out to improve a patient's quality of life, and to reduce respiratory, cardiac, endocrine, and metabolic complications encountered by those with high body mass index (BMI). A complication associated with high hypothyroidism is weight gain, which may lead to obesity. Here, we explore the effect of different bariatric procedures on thyroid function and levothyroxine dosage.  Methods This is a retrospective review of 887 patients referred to a tertiary bariatric service between 2008 and 2020 and treated for hypothyroidism at the time of referral. The study identified 57 patients on thyroxine replacement. Of these, 22 underwent restrictive bariatric procedures, 16 underwent restrictive/malabsorptive procedures, and 19 did not undergo operative intervention. Comparisons were made among each group throughout the timeline of interest. Results Out of 57 patients, 50 (87.7%) were female. The average age for patients was 47.26+/- 8.89 years. The average BMI at baseline was 48.72+/- 8.68 kg/m2. The mean dose of levothyroxine in controls was 115.8+/- 53.5 mcg while that of surgical patients was 149.8+/- 68.4 mcg. There were no statistically significant differences in levothyroxine doses between surgical and control at T0 (baseline), T1 (one-year post-op in surgical patient, or two-year post referral in control patient), T2 (two-year post-op in surgical patient, or three-year post referral in control patient), and T3 (most recent result available). The surgical group was then categorized further into restrictive and restrictive/malabsorptive. When they were compared with the control group, there were no statistically significant differences in doses. A generalized linear mixed model was applied to assess differences in levothyroxine dose with time as a random variable. This was adjusted for age, sex, BMI, T4 level, and hypothyroid cause. Through this assessment, there were several statistically significant differences in levothyroxine dosage between the groups. Control group required on average 28.06 mcg less levothyroxine than the restrictive/malabsorptive group (p=0.015). Also, the restrictive group required on average 23.57 mcg less levothyroxine than the restrictive/malabsorptive group (p=0.033). There were no statistically significant differences observed between the control group and the restrictive group (p=0.67) Conclusion Patients who have bariatric surgery have changes to their anatomy and physiology which may affect both their thyroid hormone homeostasis and levothyroxine pharmacokinetics. Thus, hypothyroid bariatric patients requiring levothyroxine must have their thyroid function monitored regularly. In this study, it was found that hypothyroid patients who underwent restrictive surgery had an overall statistically significant lower levothyroxine requirement to remain euthyroid as compared to the restrictive/malabsorptive group (p=0.033). Additionally, the control group required statistically significantly less levothyroxine than the restrictive/malabsorptive group (p=0.015). These factors may determine the type of surgery chosen by hypothyroid bariatric patients. However, further studies that are randomized, controlled, and multi-center with a higher population are required

Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

Background: We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. Results: We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Conclusions: Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status

Multimorbidity and socioeconomic deprivation in primary care consultations

Purpose: The influence of multimorbidity on the clinical encounter is poorly understood, especially in areas of high socioeconomic deprivation where burdensome multimorbidity is concentrated. The aim of the current study was to examine the effect of multimorbidity on general practice consultations, in areas of high and low deprivation. Methods: We conducted secondary analyses of 659 video-recorded routine consultations involving 25 general practitioners (GPs) in deprived areas and 22 in affluent areas of Scotland. Patients rated the GP’s empathy using the Consultation and Relational Empathy (CARE) measure immediately after the consultation. Videos were analyzed using the Measure of Patient-Centered Communication. Multilevel, multi-regression analysis identified differences between the groups. Results: In affluent areas, patients with multimorbidity received longer consultations than patients without multimorbidity (mean 12.8 minutes vs 9.3, respectively; P = .015), but this was not so in deprived areas (mean 9.9 minutes vs 10.0 respectively; P = .774). In affluent areas, patients with multimorbidity perceived their GP as more empathic (P = .009) than patients without multimorbidity; this difference was not found in deprived areas (P = .344). Video analysis showed that GPs in affluent areas were more attentive to the disease and illness experience in patients with multimorbidity (P < .031) compared with patients without multimorbidity. This was not the case in deprived areas (P = .727). Conclusions: In deprived areas, the greater need of patients with multimorbidity is not reflected in the longer consultation length, higher GP patient centeredness, and higher perceived GP empathy found in affluent areas. Action is required to redress this mismatch of need and service provision for patients with multimorbidity if health inequalities are to be narrowed rather than widened by primary care

Effectiveness of community-links practitioners in areas of high socioeconomic deprivation

PURPOSE: To assess the effect of a primary care–based community-links practitioner (CLP) intervention on patients’ quality of life and well-being. METHODS: Quasi-experimental cluster-randomized controlled trial in socioeconomically deprived areas of Glasgow, Scotland. Adult patients (aged 18 years or older) referred to CLPs in 7 intervention practices were compared with a random sample of adult patients from 8 comparison practices at baseline and 9 months. Primary outcome: health-related quality of life (EQ-5D-5L, a standardized measure of self-reported health-related quality of life that assesses 5 dimensions at 5 levels of severity). Secondary outcomes: well-being (Investigating Choice Experiments for the Preferences of Older People Capability Measure for Adults [ICECAP-A]), depression (Hospital Anxiety and Depression Scale, Depression [HADS-D]), anxiety (Hospital Anxiety and Depression Scale, Anxiety [HADS-A]), and self-reported exercise. Multilevel, multiregression analyses adjusted for baseline differences. Patients were not blinded to the intervention, but outcome analysis was masked. RESULTS: Data were collected on 288 and 214 (74.3%) patients in the intervention practices at baseline and follow-up, respectively, and on 612 and 561 (92%) patients in the comparison practices. Intention-to-treat analysis found no differences between the 2 groups for any outcome. In subgroup analyses, patients who saw the CLP on 3 or more occasions (45% of those referred) had significant improvements in EQ-5D-5L, HADS-D, HADS-A, and exercise levels. There was a high positive correlation between CLP consultation rates and patient uptake of suggested community resources. CONCLUSIONS: We were unable to prove the effectiveness of referral to CLPs based in primary care in deprived areas for improving patient outcomes. Future efforts to boost uptake and engagement could improve overall outcomes, although the apparent improvements in those who regularly saw the CLPs may be due to reverse causality. Further research is needed before wide-scale deployment of this approach

Left Ventricular Responses during Exercise in Highly Trained Youth Athletes: Echocardiographic Insights on Function and Adaptation

There is an increase in the prevalence of elite youth sports academies, whose sole aim is to develop future elite athletes. This involves the exposure of the child and adolescent athlete to high-volume training during a period of volatile growth. The large amount of data in this area has been garnered from the resting echocardiographic left ventricular (LV) evaluation of the youth athlete; while this can provide some insight on the functional adaptations to training, it is unable to elucidate a comprehensive overview of the function of the youth athletes’ LV during exercise. Consequently, there is a need to interrogate the LV responses in-exercise. This review outlines the feasibility and functional insight of capturing global indices of LV function (Stroke Index-SVIndex and Cardiac Index-QIndex), systolic and diastolic markers, and cardiac strain during submaximal and maximal exercise. Larger SVI and QI were noted in these highly trained young athletes compared to recreationally active peers during submaximal and maximal exercise. The mechanistic insights suggest that there are minimal functional systolic adaptions during exercise compared to their recreationally active peers. Diastolic function was superior during exercise in these young athletes, and this appears to be underpinned by enhanced determinants of pre-load. Keywords: in-exercise; echocardiography; highly trained; youth athlete