Minimally important differences in oral health-related quality of life after fixed orthodontic treatment: a prospective cohort study.

BACKGROUND: The minimally important difference (MID, the smallest difference that patients perceive as beneficial) has been proposed to assess whether study results are clinically meaningful, reducing the shortcoming of P-values-based approaches in the assessment of clinical outcomes. The post-treatment changes and the MID in Oral Health-Related Quality of Life (OHRQoL) among adults undergoing fixed orthodontic treatment were investigated. METHODS: Ninety-two patients (29.1 ±â€…6.3 years old, 18 males and 74 females) were prospectively included. Oral Health Impact Profile (OHIP-14) and United Kingdom Oral Health-related Quality of Life (OHQoL-UK) were used to assess OHRQoL at baseline and post-treatment (50.8 ±â€…15.7 months). Global Transition Rating (GTR) was used to assess oral health/well-being, Peer Assessment Review (PAR), and Index of Complexity, Outcome and Need (ICON) were used to assess occlusion. Wilcoxon signed-rank test was used to assess changes in OHRQoL and occlusion, Kruskal-Wallis one-way ANOVA and Mann-Whitney U-test were used to assess associations between OHRQoL and oral health/well-being or occlusion. MID for OHIP-14 and OHQoL-UK was estimated via anchor-based (PAR, ICON, GTR) and distribution-based approach (effect size, standardized response mean, standard error of measurement). RESULTS: The median OHIP-14 and OHQoL-UK post-treatment scores were significantly changed, indicating improved OHRQoL. Based on the agreement between different methods, the MID of OHIP-14 and OHQoL-UK were at least 15 and 6 scale points, corresponding to a large effect size (1.5-1.7). CONCLUSIONS: Orthodontic treatment had a positive long-term impact on OHRQoL. MID for the OHIP-14 and OHQoL-UK provide guidance to interpreting the impact of orthodontic treatment on the OHRQoL of patients.

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

Endovenous laser ablation versus mechanochemical ablation with ClariVein(®) in the management of superficial venous insufficiency (LAMA trial): study protocol for a randomised controlled trial.

BACKGROUND: Endovenous thermal techniques, such as endovenous laser ablation (EVLA), are the recommended treatment for truncal varicose veins. However, a disadvantage of thermal techniques is that it requires the administration of tumescent anaesthesia, which can be uncomfortable. Non-thermal, non-tumescent techniques, such as mechanochemical ablation (MOCA) have potential benefits. MOCA combines physical damage to endothelium using a rotating wire, with the infusion of a liquid sclerosant. Preliminary experiences with MOCA showed good results and less post-procedural pain. METHODS/DESIGN: The Laser Ablation versus Mechanochemical Ablation (LAMA) trial is a single-centre randomised controlled trial in which 140 patients will be randomly allocated to EVLA or MOCA. All patients with primary truncal superficial venous insufficiency (SVI) who meet the eligibility criteria will be invited to participate in this trial. The primary outcomes are intra-procedural pain and technical efficacy at 1 year, defined as complete occlusion of target vein segment and assessed using duplex ultrasound. Secondary outcomes are post-procedural pain, analgesia use, procedure time, clinical severity, generic and disease-specific quality of life, bruising, complications, satisfaction, cosmesis, time taken to return to daily activities and/or work, and cost-effectiveness analysis following EVLA or MOCA. Both groups will be evaluated on an intention-to-treat basis. DISCUSSION: The aim of the LAMA trial is to establish whether MOCA is superior to the current first-line treatment, EVLA. The two main hypotheses are that MOCA may cause less initial pain and disability allowing a more acceptable treatment with an enhanced recovery. The second hypothesis is that this may come at a cost of decreased efficacy, which may lead to increased recurrence and affect longer term quality of life, increasing the requirement for secondary procedures. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02627846 , registered 8 December 2015 EudraCT number: 2015-000730-30 REC ref: 15/YH/0207 R&D ref: R1788.

Lipopolysaccharide-induced nigral inflammation leads to increased IL-1ß tissue content and expression of astrocytic glial cell line-derived neurotrophic factor.

Reactive gliosis and inflammatory change is a key component of nigral dopaminergic cell death in Parkinson's disease (PD). Astrocyte derived glial cell line-derived neurotrophic factor (GDNF) promotes the survival and growth of dopaminergic neurones and it protects against or reverses nigral degeneration induced by 6-OHDA and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rodents and primates. But the effect of increased levels of pro-inflammatory cytokines on the release of GDNF is unknown. This study examined the relationship between release of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and the expression of GDNF in rats following nigral lipopolysaccharide (LPS) administration. Acute nigral administration of LPS led to marked elevation of IL-1ß but insignificant TNF-α tissue content and to a prominent expression of GDNF immunoreactivity in astrocytes but not microglia. The results suggest that inflammation is not only involved in neuronal loss but could promote neuronal survival through increased release of GDNF following up-regulation of IL-1ß.

Feasibility of a structured 3-minute walk test as a clinical decision tool for patients presenting to the emergency department with acute dyspnoea.

INTRODUCTION: Emergency department (ED) physicians face frequent decisions on whether to admit patients with congestive heart failure (CHF) or acute exacerbation of chronic obstructive pulmonary disease (COPD). This feasibility study evaluated the potential of a structured 3-minute walk test as a clinical decision tool for admission and correlated its performance with poor clinical outcomes. It also aimed to gather evidence and directions for the design of a multicentre study to derive clinical guidelines. METHODS: In this prospective cohort study, a convenience sample was enrolled of 40 adult patients who presented to a tertiary care ED with CHF, COPD, or stable chest pain and were being considered for discharge. Patients walked at their own pace and their dyspnoea, respiratory rate, heart rate and oxygen saturation were recorded each minute for 4 minutes. The primary outcome was "poor clinical outcome" defined as admission to hospital, the need for biphasic positive airway pressure, the need for intubation, relapse, or death. RESULTS: 85.0% successfully completed the test and 30.0% had poor clinical outcomes. Of those with poor clinical outcomes, 41.7% were unable to complete the test compared with only 3.6% of those with good clinical outcomes (p<0.01). Significant differences were noted in the dyspnoea (p = 0.04) and respiratory rate (p = 0.03) as well as oxygen saturation measurements at 3 minutes. CONCLUSIONS: The 3-minute walk test is a non-resource intensive, simple procedure with applicability in most ED for discharge decisions in patients with cardiopulmonary conditions. Multicentre studies are being planned to validate these findings and establish guidelines for admission and discharge of patients with CHF or acute exacerbation of COPD.

Continuous subcutaneous infusion of pramipexole protects against lipopolysaccharide-induced dopaminergic cell death without affecting the inflammatory response.

The D2/D3 dopamine receptor agonist pramipexole, protects against toxin-induced dopaminergic neuronal destruction but its mechanism of action is unknown. Inflammation following glial cell activation contributes to cell death in Parkinson's disease and we now report on the effects of acute or chronic administration of pramipexole on lipopolysaccharide (LPS) induced inflammation and nigral dopaminergic cell death in the rat. At 48 h and 30 days following supranigral administration of LPS, approximately 70% of tyrosine hydroxylase (TH) immunoreactive (-ir) cells in substantia nigra had degenerated with a corresponding loss of TH-ir terminals in the striatum. In rats acutely treated with pramipexole (2x1 mg/kg; s.c.) 48 h following LPS application, there was no difference in the number of TH-ir cells or terminals compared to LPS-treated rats receiving vehicle. However, the continuous subcutaneous infusion of pramipexole for 7 days prior to LPS and 21 days subsequently, produced a marked preservation of both TH-ir cells and terminals. At 48 h or 30 days, LPS induced an up-regulation of ubiquitin-ir within the nigral TH-ir neurones, which was reduced by pramipexole treatment. Thirty days following supranigral LPS administration (9 days after the end of infusion), (+)-amphetamine (5 mg/kg, i.p.) caused robust ipsiversive rotation. In rats treated with LPS but receiving continuous subcutaneous administration of pramipexole, (+)-amphetamine-induced rotation was markedly reduced. LPS-induced increase in the levels of inflammatory markers, were not affected by either acute administration or continuous infusion of pramipexole. Continuous infusion of pramipexole protected dopaminergic neurones against inflammation induced degeneration but without modification of the inflammatory response.

The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation.

Sustained reactive microgliosis may contribute to the progressive degeneration of nigral dopaminergic neurons in Parkinson's disease (PD), in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed human and in non-human primates. However, the temporal relationship between glial cell activation and nigral cell death is relatively unexplored. Consequently, the effects of acute (24 h) and chronic (30 days) glial cell activation induced by unilateral supranigral lipopolysaccharide (LPS) administration were studied in rats. At 24 h, LPS administration caused a marked reduction in the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra (SN) but striatal TH-ir was unaffected. By 30 days, the loss of TH-positive neurons in the LPS-treated nigra was no greater than at 24 h although a heterogeneous loss of striatal TH-ir was present. The loss of nigrostriatal neurons was of functional significance, as at 30 days, LPS-treated rats exhibited ipsiversive circling in response to (+)-amphetamine administration. At 24 h, there was a moderate increase in glial fibrillary acidic protein (GFAP)-ir astrocytes in the SN but a marked elevation of p47phox positive OX-42-ir microglia, and intense inducible nitric oxide synthase (iNOS)-ir and 3-nitrotyrosine (3-NT)-ir was present. However, by 30 days the morphology of OX-42-ir microglia returned to a resting state, the numbers were greatly reduced and no 3-NT-ir was present. At 30 days, GFAP-ir astrocytes were markedly increased in number and iNOS-ir was present in fibrillar astrocyte-like cells. This study shows that acute glial activation leading to dopaminergic neuron degeneration is an acute short-lasting response that does not itself perpetuate cell death or lead to prolonged microglial activation.

The Canadian C-spine rule for radiography in alert and stable trauma patients.

CONTEXT: High levels of variation and inefficiency exist in current clinical practice regarding use of cervical spine (C-spine) radiography in alert and stable trauma patients. OBJECTIVE: To derive a clinical decision rule that is highly sensitive for detecting acute C-spine injury and will allow emergency department (ED) physicians to be more selective in use of radiography in alert and stable trauma patients. DESIGN: Prospective cohort study conducted from October 1996 to April 1999, in which physicians evaluated patients for 20 standardized clinical findings prior to radiography. In some cases, a second physician performed independent interobserver assessments. SETTING: Ten EDs in large Canadian community and university hospitals. PATIENTS: Convenience sample of 8924 adults (mean age, 37 years) who presented to the ED with blunt trauma to the head/neck, stable vital signs, and a Glasgow Coma Scale score of 15. MAIN OUTCOME MEASURE: Clinically important C-spine injury, evaluated by plain radiography, computed tomography, and a structured follow-up telephone interview. The clinical decision rule was derived using the kappa coefficient, logistic regression analysis, and chi(2) recursive partitioning techniques. RESULTS: Among the study sample, 151 (1.7%) had important C-spine injury. The resultant model and final Canadian C-Spine Rule comprises 3 main questions: (1) is there any high-risk factor present that mandates radiography (ie, age >/=65 years, dangerous mechanism, or paresthesias in extremities)? (2) is there any low-risk factor present that allows safe assessment of range of motion (ie, simple rear-end motor vehicle collision, sitting position in ED, ambulatory at any time since injury, delayed onset of neck pain, or absence of midline C-spine tenderness)? and (3) is the patient able to actively rotate neck 45 degrees to the left and right? By cross-validation, this rule had 100% sensitivity (95% confidence interval [CI], 98%-100%) and 42.5% specificity (95% CI, 40%-44%) for identifying 151 clinically important C-spine injuries. The potential radiography ordering rate would be 58.2%. CONCLUSION: We have derived the Canadian C-Spine Rule, a highly sensitive decision rule for use of C-spine radiography in alert and stable trauma patients. If prospectively validated in other cohorts, this rule has the potential to significantly reduce practice variation and inefficiency in ED use of C-spine radiography.