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The first signs of diabetic neuropathy typically result from small-diameter nerve fiber dysfunction. This review synthesized the evidence for small-diameter nerve fiber neuropathy measured via quantitative sensory testing (QST) in patients with diabetes with and without painful and non-painful neuropathies. Electronic databases were searched to identify studies in patients with diabetes with at least one QST measure reflecting small-diameter nerve fiber function (thermal or electrical pain detection threshold, contact heat-evoked potentials, temporal summation or conditioned pain modulation). Four groups were compared: patients with diabetes (1) without neuropathy, (2) with non-painful diabetic neuropathy, (3) with painful diabetic neuropathy and (4) healthy individuals. Recommended methods were used for article identification, selection, risk of bias assessment, data extraction and analysis. For the meta-analyses, data were pooled using random-effect models. Twenty-seven studies with 2422 participants met selection criteria; 18 studies were included in the meta-analysis. Patients with diabetes without symptoms of neuropathy already showed loss of nerve function for heat (standardized mean difference (SMD): 0.52, p

Background: Low back pain (LBP) has the highest global burden of disease related to years lived with disability worldwide. Given the significant personal, social and economic burden associated with LBP, delivering efficient and effective healthcare is crucial. Clinical practice guidelines recommend a biopsychosocial management approach, incorporating active self-management strategies including education and exercise. Despite the evidence underpinning this approach showing promise, there are still significant challenges faced by clinicians when managing persistent LBP. There is increasing interest in the potential for a more stratified care approach, relying on early prognostic screening to help guide clinical decisions. In primary healthcare settings, prognostic screening for LBP has been shown to improve patient outcomes and reduce healthcare costs. However, there is a lack of knowledge about prognostic factors that influence recovery in people with persistent LBP in secondary healthcare. Therefore, this thesis aims to develop prognostic models to determine at baseline which patients with persistent LBP are likely to have a good and poor outcome to a 5-week program of combined education and exercise (‘UPLIFT’) delivered in a secondary healthcare setting. Methods: A prospective cohort study of 246 people with persistent LBP (defined as LBP > 3 months) was conducted in a secondary healthcare outpatient setting. Participants were recruited from a physiotherapy-led neurosurgical screening clinic. Demographic data, medical history and psychosocial characteristics were recorded at baseline and were considered as potential prognostic variables. Specifically, fear avoidance beliefs, pain self-efficacy, LBP treatment beliefs, pain catastrophising, perceived injustice, depression, anxiety and stress, disability level, pain intensity and interference, health status and social connectedness were assessed using self-reported questionnaires. Participants attended the UPLIFT program, consisting of five weekly 90-minute group sessions that combine interactive education sessions (~60 mins each) and a graded exercise program (~30 mins each). The primary outcome measure to identify good and poor outcome was the Global Rating of Change (GROC) scale, which ranged from +5 (completely recovered) to -5 (very much worse), assessed at the completion of the UPLIFT program. A good outcome was defined as GROC score ≥ +3; a poor outcome was defined as a GROC score < +3. Prognostic models were developed using multivariable logistic regression analyses, with bootstrapping techniques for internal validation. The performance of the models was determined by the explained variance (Nagelkerke R2) and the accuracy of the model, measured by the area under the receiver operating characteristic curve. Furthermore, using paired t-tests, we determined whether participation in the UPLIFT program was associated with improvements in psychosocial characteristics which were collected at baseline and immediately post-intervention. Findings: The distribution of people with good (49%) and poor outcome (51%) was in line with a-priori assumptions and optimal to derive prediction models. The multivariable prognostic model for good and poor outcome both contained five baseline predictors (self-efficacy; catastrophising; pain intensity; depression, anxiety and stress; fear-avoidance). People with high self-efficacy and pain catastrophising scores had increased odds of a good outcome immediately following the program, whereas people with high pain intensity, fear-avoidance and depression, anxiety and stress scores had decreased odds of a good outcome. Further, people with high self-efficacy and pain catastrophising scores had decreased odds of a poor outcome, whereas people with high pain intensity, fear-avoidance and depression, anxiety and stress scores had increased odds of a poor outcome immediately following the UPLIFT program. Following bootstrapping techniques, the explained variance of both models was low (R2 = 0.07) and the area under the curve indicated poor discrimination (0.68). Immediately on completion of the UPLIFT program, all psychosocial variables showed positive improvements (p