Revisions of Extensive Acetabular Defects with Impaction Grafting and a Cement Cup

Item does not contain fulltextBACKGROUND: Loosening of acetabular components often leads to bony defects. Management of extensive acetabular bone loss in hip revision arthroplasty can be a tremendous challenge. QUESTIONS/PURPOSES: We asked whether a reconstruction with impacted bone grafts will provide a durable and pain-free function in extensive acetabular defects. We specifically determined the (1) survival rates with the end point of revision for any reason, aseptic revision, and radiographic loosening; (2) visual analog scale (VAS) pain score, Harris hip score (HHS), and the Oxford Hip Questionnaire score (OHQS); (3) number of repeat revisions; (4) complications; and (5) radiographic loosening, wear, and radiolucencies. PATIENTS AND METHODS: We retrospectively followed 25 patients (27 hips) with extensive acetabular defects. No patient was lost to followup. Two patients died during followup. Minimum followup was 3 years (mean, 8.8 years; range, 3-14.1 years). RESULTS: Three patients (three hips) underwent repeat revision surgery and another two patients (two hips) had radiographically loose hips. The 10-year survival rate was 88% (95% confidence interval, 74.2%-100%) with the end point acetabular revision for any reason and 95% (95% confidence interval, 86.0%-100%) with the end point acetabular revision for aseptic loosening. The mean HHSs were 55 points before surgery and 72 points postoperatively. CONCLUSIONS: Acetabular reconstruction with impaction bone grafting and a cemented cup is a reliable technique with a 10-year survival rate of 88% in patients with extensive acetabular deficiencies. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines for Authors for a complete description of levels of evidence

Development and Process Evaluation of a 5-Week Exercise Program to Prevent Falls in People after Stroke: The FALLS Program

Falls are a common complication after stroke, with balance and gait deficits being the most important risk factors. Taking into account the specific needs and capacities of people with stroke, we developed the FALLS program (FALL prevention after Stroke), based on the “Nijmegen falls prevention program” (a proven-effective 5-week exercise program designed for community-dwelling elderly people). The program was tested in twelve community-dwelling persons with stroke, and a process evaluation was conducted with patients, trainers, health care professionals, and managers. The FALLS program was considered suitable and feasible by people with stroke in the study and relevant health care professionals, and recommendations for implementation in clinical practice have been suggested

Stability analysis of clustering of Norris' visual analogue scale: applying the consensus clustering approach

Visual analogue scales are widely used to measure subjective responses. Norris' 16 visual analogue scales (N_VAS) measure subjective feelings of alertness and mood. Up to now, different scientists have clustered items of N_VAS into different ways and Bond and Lader's way has been the most frequently used in clinical research. However, there are concerns about the stability of this clustering over different subject samples and different drug classes. The aim of this study was to test whether Bond and Lader's clustering was stable in terms of subject samples and drug effects. Alternative clustering of N_VAS was tested. Data from studies with 3 types of drugs: cannabinoid receptor agonist (delta-9-tetrahydrocannabinol [THC]), muscarinic antagonist (scopolamine), and benzodiazepines (midazolam and lorazepam), collected between 2005 and 2012, were used for this analysis. Exploratory factor analysis (EFA) was used to test the clustering algorithm of Bond and Lader. Consensus clustering was performed to test the stability of clustering results over samples and over different drug types. Stability analysis was performed using a three-cluster assumption, and then on other alternative assumptions. Heat maps of the consensus matrix (CM) and density plots showed instability of the three-cluster hypothesis and suggested instability over the 3 drug classes. Two- and four-cluster hypothesis were also tested. Heat maps of the CM and density plots suggested that the two-cluster assumption was superior. In summary, the two-cluster assumption leads to a provably stable outcome over samples and the 3 drug types based on the data used.Stress-related psychiatric disorders across the life spa

Effects of mexiletine and lacosamide on nerve excitability in healthy subjects: a randomized, double-blind, placebo-controlled, crossover study

Selective voltage-gated sodium channel blockers are of growing interest as treatment for pain. For drug development of such compounds, it would be critical to have a biomarker that can be used for proof-of-mechanism. We aimed to evaluate whether drug-induced changes in sodium conductance can be detected in the peripheral nerve excitability profile in 18 healthy subjects. In a randomized, double-blind, 3-way crossover study, effects of single oral doses of 333 mg mexiletine and 300 mg lacosamide were compared with placebo. On each study visit, motor and sensory nerve excitability measurements of the median nerve were performed (predose; and 3 and 6 hours postdose) using Qtrac. Treatment effects were calculated using an analysis of covariance (ANCOVA) with baseline as covariate. Mexiletine and lacosamide had significant effects on multiple motor and sensory nerve excitability variables. Depolarizing threshold electrotonus (TEd40 (40–60 ms)) decreased by mexiletine (estimated difference (ED) −1.37% (95% confidence interval (CI): −2.20, −0.547; P = 0.002) and lacosamide (ED −1.27%, 95% CI: −2.10, −0.443; P = 0.004) in motor nerves. Moreover, mexiletine and lacosamide decreased superexcitability (less negative) in motor nerves (ED 1.74%, 95% CI: 0.615, 2.87; P = 0.004, and ED 1.47%, 95% CI: 0.341, 2.60; P = 0.013, respectively). Strength-duration time constant decreased after lacosamide in motor- (ED −0.0342 ms, 95% CI: −0.0571, −0.0112; P = 0.005) and sensory nerves (ED −0.0778 ms, 95% CI: −0.116, −0.0399; P < 0.001). Mexiletine and lacosamide significantly decrease excitability of motor and sensory nerves, in line with their suggested mechanism of action. Results of this study indicate that nerve excitability threshold tracking can be an effective pharmacodynamic biomarker. The method could be a valuable tool in clinical drug development

Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched

Purpose: Fractal analysis can be used to quantitatively analyze the retinal microvasculature and might be a suitable method to quantify retinal capillary changes in sickle cell disease (SCD) patients. Retinal oximetry measurements might function as a proxy for the pathophysiology of cerebrovascular diseases. Moreover, hypoxia has an important role in the pathophysiology of diabetic and other retinopathies. However, little is known about the oximetry around the macula in SCD patients. With this study, we explored the feasibility to perform these quantified measurements in SCD patients. Methods: Retinal microvascular and oximetry measurements were performed in eight SCD patients and eight healthy matched controls. Oximetry pictures and non-invasive capillary perfusion maps (nCPM) were obtained by the retinal function imager. Measurements were conducted twice on two different study days. Measured variables included monofractal dimension (Dbox), relative saturation, deoxygenated hemoglobin (deoxyHb), and oxygenated hemoglobin (oxyHb) concentration. Results: No statistically significant differences in vessel density were found in the different annular zones (large vessels, p = 0.66; small vessels, p = 0.66) and anatomical quadrants (large vessels, p = 0.74; small vessels, p = 0.72). Furthermore, no significant between-group differences were found in the other different anatomical quadrants and annular zones around the fovea for relative saturation levels and deoxygenated Hb. However, the oxyHb levels were significantly lower in SCD patients, compared with those in matched controls in the temporal quadrants (p = 0.04; p = 0.02) and the superior nasal quadrant (p = 0.05). Conclusions: Our study demonstrated the feasibility of multispectral imaging to measure retinal changes in oxygenation in both SCD patients and matched volunteers. The results suggest that in SCD patients before any structural microvascular changes in the central retina are present, functional abnormalities can be observed with abnormal oximetry measurements

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [90Y-DOTA0,Tyr3]octreotide may result in partial remissions in 10–25% of patients. The newer analogue [DOTA0,Tyr3]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0,Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide 177Lu, it has proved very successful in achieving tumour regression in animal models. The effects of 177Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3–6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi 177Lu-octreotate, to a final cumulative dose of 600–800 mCi, with treatment intervals of 6–9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with 177Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression

Conflict in the Indian Kashmir Valley I: exposure to violence

ABSTRACT: BACKGROUND: India and Pakistan have disputed ownership of the Kashmir Valley region for many years, resulting in several conflicts since the end of partition in 1947. Very little is known about the prevalence of violence and insecurity in this population. METHODS: We undertook a two-stage cluster household survey in two districts (30 villages) of the Indian part of Kashmir to assess experiences with violence and mental health status among the conflict-affected Kashmiri population. The article presents our findings for confrontations with violence. Data were collected for recent events (last 3 months) and those occurring since the start of the conflict. Informed consent was obtained for all interviews. RESULTS: 510 interviews were completed. Respondents reported frequent direct confrontations with violence since the start of conflict, including exposure to crossfire (85.7%), round up raids (82.7%), the witnessing of torture (66.9%), rape (13.3%), and self-experience of forced labour (33.7%), arrests/kidnapping (16.9%), torture (12.9%), and sexual violence (11.6%). Males reported more confrontations with violence than females, and had an increased likelihood of having directly experienced physical/mental maltreatment (OR 3.9, CI: 2.7-5.7), violation of their modesty (OR 3.6, CI: 1.9-6.8) and injury (OR 3.5, CI: 1.4-8.7). Males also had high odds of self-being arrested/kidnapped (OR 8.0, CI: 4.1-15.5). CONCLUSION: The civilian population in Kashmir is exposed to high levels of violence, as demonstrated by the high frequency of deliberate events as detention, hostage, and torture. The reported violence may result in substantial health, including mental health problems. Males reported significantly more confrontations with almost all violent events; this can be explained by higher participation in outdoor activities

Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers

The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty-four healthy male volunteers received a two-and-a-half-day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two-and-a-half-day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti-inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti-inflammatory effects of such compounds in a minimally invasive manner