The effect of dynamic ankle-foot orthoses on the balance and gait of stroke patients

The present research aimed to assess the effects of a novel type of orthosis, the Dynamic Ankle Foot Orthosis (DAFO), on the balance and gait characteristics of hemiparetic subjects. The DAFO is a low splint with a custom-moulded insole, which is believed to support foot alignment, ankle supination-pronation and provide minimal restriction of the ankle joint flexion-extension. It was hypothesised that DAFOs improve motor behaviour after stroke involving the acquisition of standing balance (hypothesis I) and gait (hypothesis II) compared with using shoes. It was proposed that users' subjective opinions of DAFOs would support the findings of the device's ability to modify human performance such that they are beneficial when used as a part of rehabilitation management for stroke patients (hypothesis III). Twenty-two stroke subjects were randomly allocated to experimental (with DAFO and shoes-only) and control (using shoes-only) groups. Subjects followed twelve weeks of experimental trials comprising three data collections. The testing procedure was developed from preliminary work, which involved a pilot study and reliability tests. Standing balance was measured using forceplatform apparatus. The parameters investigated were: the velocity and sway index of the CoP, and F(mean), F(sd) and F(slope) of shear forces. Kinematic gait performance was assessed using a 3-D four-camera motion measurement system. The parameters studied were: the gait velocity, stride length, step length, cadence, and single stance phase, together with the minimum/maximum values of the angular displacement and velocity of the foot, shank, and thigh segments in the saggittal plane during two strides. An open questionnaire was used to evaluate subjects' opinions regarding the use of DAFOs. Overall, the quantitative studies did not identify consistent and statistically significant differences between the two experimental situations for these groups of patients. In the studies of balance, none of the parameter comparisons analysed within- and between- groups achieved statistical significance. In the studies of gait, statistically significant differences were identified for some (but not all) parameters. It is unknown whether any single or combination of balance and gait variables can be used to describe human gait entirely. On this basis, hypotheses I and II were rejected. However, these are tentative conclusions. Thus, difficulties in maintaining the stroke subject cohort number for these studies meant that the analyses probably lacked sufficient statistical power to detect small but potentially important differences in DAFO mediated actions. Furthermore, in several cases, clear differences in the magnitude of balance and gait parameters between DAFO and shoe users were apparent, and these differences were often consistent with nearer normal levels associated with use of the device (suggesting potentially beneficial influences). Thus, positive effects of the DAFO on lateral velocity of sway and variability of the spectral frequency were evident for some subjects. The gait velocity, stride length and single stance phase were also nearer normal values using DAFOs than without them. In addition, the maximum foot velocity value was improved in the middle of swing phase on the affected side, which may indicate improvement to the ankle dorsiflexion function using these devices. In contrast to the inconclusive balance and gait findings, the outcome of the questionnaire assessments was clear. The majority of subjects provided very positive feedback with regard to DAFO use. Most subjects expressed confidence in the splint, which they perceived as helpful for their walking ability in day life. Some difficulties were noticed with donning and doffing the DAFO, but the perceived benefits outweighed this consideration. These qualitative studies therefore provide the most convincing evidence to support the idea that DAFOs improve stroke patients' balance and gait, and that this type of orthosis may form a useful adjunct to rehabilitation strategies. However, as the proposals set out for this research were related, acceptance of hypothesis III requires that at least one of the preceding hypotheses be accepted. On this basis, hypothesis III was also rejected. In conclusion, although this work failed overall to demonstrate a significant effect of DAFOs on the rehabilitation of stroke patients, the anecdotal evidence obtained adds to knowledge in this field. The research identified some parameters of balance and gait, which might be influenced by the device in a beneficial manner. These parameters may be more useful to use in future investigations. The reasons for the discrepant outcomes of the quantitative and qualitative studies are unclear. However, it is suggested that there may be uncontrolled variables within either the patient group or in the DAFOs (or both) which mean that some DAFOs work better than others. It is proposed that further studies of the DAFO are warranted.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Inverse Modeling for MEG/EEG data

We provide an overview of the state-of-the-art for mathematical methods that are used to reconstruct brain activity from neurophysiological data. After a brief introduction on the mathematics of the forward problem, we discuss standard and recently proposed regularization methods, as well as Monte Carlo techniques for Bayesian inference. We classify the inverse methods based on the underlying source model, and discuss advantages and disadvantages. Finally we describe an application to the pre-surgical evaluation of epileptic patients.Comment: 15 pages, 1 figur

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

Centralized repeated resectability assessment of patients with colorectalliver metastases during first-line treatment : prospective study

Y Background: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.Peer reviewe

Factors associated with self-assessed increase in tobacco consumption among over-indebted individuals in Germany: a cross-sectional study

Background Over-indebtedness is an increasing phenomenon in industrialised nations causing individual hardship and societal problems. Nonetheless, few studies have explored smoking among over-indebted individuals. Methods A cross-sectional survey (n=949) on retrospectively assessed changes in tobacco consumption was carried out in 2006 and 2007 among clients of 84 officially approved debt and insolvency counselling centres in Germany (response rate 39.7%). Logistic regressions were performed to explore factors associated with reports of increased smoking after onset of over-indebtedness. Results 63% of all respondents stated daily or occasional tobacco consumption. Almost one fifth reported an increase in smoking after becoming over-indebted. Females were less likely to report increased smoking than men (aOR 0.66, 95% CI 0.44-0.99) whereas respondents who had been over-indebted for more than 10 years were more likely to report increased smoking than those who had been over-indebted for less than five years (aOR 1.66; 95%-CI 1.00-2.76). The odds of increased smoking were also elevated among those who reported that their families and friends had withdrawn from them as a consequence of their over-indebtedness (aOR 1.82; 95%-CI 1.06-3.14). Conclusions The study identifies over-indebted individuals and particularly over-indebted men as a high-risk group of smokers. Low levels of social embeddedness/support were associated with a further increase in smoking after becoming over-indebted. Given recent increases of over-indebtedness, the findings highlight the need to develop appropriate public health policies

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival.Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS).Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy.Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.</p

Centralized repeated resectability assessment of patients with colorectalliver metastases during first-line treatment: prospective study

Background: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases.Methods: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival.Results: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively.Conclusion: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.</p

Health-Related Quality of Life in Metastatic Colorectal Cancer Patients Treated with Curative Resection and/or Local Ablative Therapy or Systemic Therapy in the Finnish RAXO-Study

Simple Summary Metastatic colorectal cancer is the second most common cause of cancer death. Long-term survival and cure can be achieved after intensive treatments, including metastasectomy, i.e., the removal of all metastases. We wanted to clarify whether a patient health-related quality of life (HRQoL) was reduced by treatments that aimed to maximise metastasectomy rates, and whether HRQoL of treated patients is comparable to the general population. In a cross-sectional study of 444 patients (1751 questionnaires) in the RAXO-study population, we show that HRQoL of intensively treated patients, sometimes with multiple and multisite metastasectomies-usually combined with systemic therapy-remains at a high level during and after curative treatment and when compared with the general population. Good HRQoL was also seen during non-curative treatment from first- to later-lines, with an impaired HRQoL only at end-of-life. Thus, we should aim at maximising metastasectomies since they give long-term survival and sometimes cure with a high HRQoL. Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89-0.91 with the 15D, 0.85-0.87 with the EQ-5D, 68-80 with the EQ-5D-VAS, and 68-79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors' well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.</p