Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review

OBJECTIVE: To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. DESIGN: Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt-Estes scores with thresholds for a positive test of > or =4 points or > or =5 points. DATA SOURCES: Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. STUDY SELECTION: Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. DATA EXTRACTION: Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. DATA SYNTHESIS: Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. RESULTS: 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold > or =4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. CONCLUSION: Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension.

Mechanical chondroplasty: early metabolic consequences in vitro

PURPOSE: The purpose of this study was to determine the depth of penetration from mechanical chondroplasty and metabolic consequences of this procedure on the remaining articular cartilage. METHODS: Mechanical chondroplasty was performed in vitro on a portion of fresh grade I or II articular cartilage from 8 human knee arthroplasty specimens. Treated and control (untreated) explants (approximately 30 mg) were cut from the cartilage. The explants were divided into 2 groups, day 1 and day 4, placed separately in a 48-well plate containing media, and incubated at 37 degrees C for 24 hours. After the 24-hour incubation, the explants were weighed on day 1 and day 4, and explant media were removed and tested for total proteoglycan synthesis and aggrecan synthesis. At time 0, 2 sets (2.6 mm each) of treated and control cartilage slices were cut with a precision saw. One set was stained for confocal laser microscopy via a cytotoxicity stain to determine cell viability. The second set was stained with H;E to determine depth of penetration. RESULTS: The mean depth of penetration was 252.8 +/- 78 microm. There was no significant difference (P > .25) between total proteoglycan synthesis for control versus treatment groups on day 1 or 4. Aggrecan synthesis was significantly reduced on day 1 when normalized for tissue weight (P = .019) and double-stranded deoxyribonucleic acid (P = .004). On day 4, no significant difference was detected. Confocal laser microscopy did not show cell death below the zone of treatment. CONCLUSIONS: There was no significant metabolic consequence caused by chondroplasty to the remaining articular cartilage, and the zone of injury was limited to the treatment area. CLINICAL RELEVANCE: Mechanical chondroplasty causes no significant metabolic consequences to articular cartilage under these conditions.

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Reattachment of the tuberosities with cable wires and bone graft in hemiarthroplasties done for proximal humeral fractures with cable wire and bone graft: 58 patients with a 22-month minimum follow-up

OBJECTIVE: The stability of 2 fixation techniques for the tuberosities in patients with 3- or 4-part proximal humerus fractures treated with hemiarthroplasties was compared. DESIGN: Retrospective review of a nonrandomized sequential series of patients. SETTING: Level I university orthopaedic surgery department. PATIENTS: A consecutive series of 58 patients (average age, 64 years) from 1990 to 1999 with 3- and 4-part fractures of the proximal humerus. INTERVENTION: In group 1, 31 patients were treated with either a Neer or Aequalis shoulder prosthesis using nonabsorbable sutures and no bone graft for the reattachment of the tuberosities. In group 2, 27 patients were treated with either an Aequalis or Epoca shoulder prosthesis and a combination of cable fixation and bone grafting. MAIN OUTCOME MEASUREMENTS: At follow-up (average, 32 months), radiographs were taken to confirm tuberosity fixation or degree of displacement or resorption. Functional outcome was assessed by the Constant-Murley Score. RESULTS: Significantly more dislocated tuberosities were found radiographically in group 1 (10 of 13 in total, P = 0.011), and significantly more tuberosities were resorbed in group 1 (9 of 12 in total, P = 0.012). Significant differences in functional results among healed versus failed tuberosity fixation were observed for activity of daily living (P = 0.05), range of motion (P = 0.002), strength (P = 0.01), the total score (P = 0.008), and the passive rotation amplitude (P = 0.04). CONCLUSION: In hemiarthroplasties for proximal humeral fractures, the reattachment of the tuberosities with cable wire and bone grafting gives consistently better radiographic and functional results than with suture fixation alone.

Early prognostic value of the medical emergency team calling criteria in patients admitted to intensive care from the emergency department

OBJECTIVES: To evaluate the early prognostic value of the medical emergency team (MET) calling criteria in patients admitted to intensive care from the emergency department. DESIGN: Retrospective cohort study. SETTING: Emergency department and department of intensive care medicine of a 960-bed tertiary referral hospital. PATIENTS: A total of 452 consecutive adult patients admitted to intensive care from the emergency department from January 1, 2004, to December 31, 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MET calling criteria were retrospectively extracted from patient records, and the sum of positive criteria was calculated for the first hour in the emergency department (METinitial) and subsequently until admission to the intensive care unit in a series of time periods. The maximum number of positive MET calling criteria during any time period was defined (METmax). Logistic regression analysis revealed METinitial (odds ratio [OR] 3.392, 95% confidence interval [CI] 2.534-4.540) and METmax (OR 3.867, 95% CI 2.816-5.312) to be significant predictors of hospital mortality, the need for mechanical ventilation (METinitial: OR 4.151, 95% CI 3.53-4.652; METmax: OR 4.292, 95% CI 3.151-5.846), and occurrence of hemodynamic instability (METinitial: OR 1.548, 95% CI 1.258-1.905; METmax: OR 1.685, 95% CI 1.355-2.094) (all p < .0001). CONCLUSIONS: MET scores collected early after admission or throughout the stay in the emergency department allow for simple identification of patients at risk of unfavorable outcome during the subsequent intensive care unit stay.

rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants

BACKGROUND: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. METHODS: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). RESULTS: All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. CONCLUSION: IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

Thermodilution and esophageal Doppler ultrasound in the assessment of blood flow changes induced by endotoxin and dobutamine

BACKGROUND: Intermittent (IT) and continuous (CT) thermodilution and esophageal Doppler (ED), are all used for hemodynamic monitoring. The aim of this study was to test the agreement between these methods during endotoxin (ET) and dobutamine infusion. METHODS: Twenty-two pigs (39 +/- 1.8 kg body weight) were randomized to general anesthesia and either continuous ET (n = 9) or placebo (PL, n = 13) infusion. After 18 hours of ET or PL infusion, the animals were further randomized to receive dobutamine (n = 3 in ET, n = 5 in PL) or PL. A set of measurements using the three methods were obtained every hour, and the relative blood flow changes between two subsequent measurements were calculated. RESULTS: Bias or limits of agreement for flows were 0.73 L/min or 1.80 L/min for IT and CT, -0.33 L/min or 4.29 L/min for IT and ED, and -1.06 or 3.94 for CT and ED (n = 515, each). For flow changes they were 1% or 44%, 2% or 59%, and 3% or 45%, respectively. Bias and limits of agreement did not differ in ET- and PL-treated animals or in animals with or without dobutamine. Despite significant correlation between any two methods, the respective correlation coefficients (r) were small (IT vs. CT: 0.452; IT vs. ED: 0.042; CT vs. ED: 0.069; all p < 0.001). The same directional changes were measured by any two methods in 49%, 40%, and 50%. When IT flows >5 L/min were compared with IT flows ormer (p = 0.012). CONCLUSION: IT and CT cardiac output agree only to a moderate level, and agreement between the respective relative blood flow changes is even worse. ED has poor agreement with both thermodilution methods, especially when cardiac output is >5 L/min.

Bone apposition around two different sandblasted and acid-etched titanium implant surfaces: a histomorphometric study in canine mandibles

PURPOSE: The aim of this study was to evaluate bone apposition to a modified sandblasted and acid-etched (SLA) implant surface (modSLA) in the canine mandible as compared with the standard SLA surface. MATERIAL AND METHODS: In this experimental study, all mandibular premolars and first molars were extracted bilaterally in five foxhounds. After a healing period of 6 months, each side of the mandible received six randomly assigned dental implants alternating between the standard SLA and modSLA surface. The dogs were sacrificed at 2 weeks (n=2) or 4 weeks (n=3) after implant placement. Histologic and histomorphometric analyses were then performed for each implant. RESULTS: The microscopic healing patterns at weeks 2 and 4 for the two implant types with the standard SLA and modSLA surfaces showed similar qualitative findings. New bone tissue had already established direct contact with implant surfaces after 2 weeks of healing. The mean percentage of newly formed bone in contact with the implant (BIC) was significantly greater for modSLA (28.2+/-7.9%) than for SLA (22.2+/-7.3%) (P<0.05). This difference was no longer evident after 4 weeks. An increase in BIC for both implant surface types occurred from weeks 2 to 4. This increase was statistically significant when compared with SLA at 2 weeks (P<0.05), but not when compared with modSLA at 2 weeks. CONCLUSION: The data from the present study demonstrate significantly more bone apposition for the modSLA surface than the standard SLA surface after 2 weeks of healing. This increased bone apposition may allow a further reduction of the healing period following implant placement for patients undergoing early loading procedures.

Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter, phase II trial of the Swiss Group for Clinical Cancer Research

PURPOSE: To evaluate the effects of palliative chemotherapy with gemcitabine plus capecitabine (GemCap) on patient-reported outcomes measured using clinical benefit response (CBR) and quality-of-life (QOL) measures in patients with advanced biliary tract cancer. PATIENTS AND METHODS: Patients had to manifest symptoms of advanced biliary tract cancer and have at least one of the following: impaired Karnofsky performance score (60 to 80), average analgesic consumption >or= 10 mg of morphine equivalents per day, and average pain intensity score of >or= 20 mm out of 100 mm. Treatment consisted of oral capecitabine 650 mg/m(2) twice daily on days 1 through 14 plus gemcitabine 1,000 mg/m(2) as a 30-minute infusion on days 1 and 8 every 3 weeks until progression. The primary end point was the number of patients categorized as having a CBR or stable CBR (SCBR) during the first three treatment cycles. RESULTS: Forty-four patients were enrolled (bile duct cancer, n = 36; gallbladder cancers, n = 8). The main grade 3 or 4 adverse events included hematologic toxicity and fatigue. After three cycles, 36% of patients achieved a CBR, and 34% achieved an SCBR. Over the full course of treatment, 57% of patients achieved a CBR, and 18% achieved an SCBR. Improved QOL was observed in patients with a CBR or SCBR. The objective response rate was 25%. Median time to progression and overall survival times were 7.2 months and 13.2 months, respectively. CONCLUSION: Chemotherapy with GemCap is well tolerated and effective and leads to a high CBR rate. Patient-reported outcomes are useful for evaluating the effects of palliative chemotherapy in patients with biliary tract cancer.

Indole based antioxidants for the treatment of ischemia reperfusion injury

With the number of ischemia reperfusion (I/R) injuries on the rise, and a lack of pharmacological intervention aimed at reducing free radical damage associated with I/R, we have developed 30 indole phenolic antioxidants that were synthesized by click chemistry to couple our indole with a phenolic or anisole derivative. The total antioxidant activity of the analogues was tested in vitro using the ferric thiocyanate lipid emulsion method. Compounds containing hydroxyl or methoxy aromatics at the 3 or 4 position on the aromatic coupled to the indole exhibited increased antioxidant scavenging. 4-methoxyindole derivatives (8a-e) exhibited increased scavenging (p < 0.05) compared to the known antioxidant butylated hydroxyanisole (BHA).

Preclinical disability as a risk factor for falls in community-dwelling older adults

BACKGROUND: Falls are common and serious problems in older adults. The goal of this study was to examine whether preclinical disability predicts incident falls in a European population of community-dwelling older adults. METHODS: Secondary data analysis was performed on a population-based longitudinal study of 1644 community-dwelling older adults living in London, U.K.; Hamburg, Germany; Solothurn, Switzerland. Data were collected at baseline and 1-year follow-up using a self-administered multidimensional health risk appraisal questionnaire, including validated questions on falls, mobility disability status (high function, preclinical disability, task difficulty), and demographic and health-related characteristics. Associations were evaluated using bivariate and multivariate logistic regression analyses. RESULTS: Overall incidence of falls was 24%, and increased by worsening mobility disability status: high function (17%), preclinical disability (32%), task difficulty (40%), test-of-trend p <.003. In multivariate analysis adjusting for other fall risk factors, preclinical disability (odds ratio [OR] = 1.7, 95% confidence interval [CI], 1.1-2.5), task difficulty (OR = 1.7, 95% CI, 1.1-2.6) and history of falls (OR = 4.7, 95% CI, 3.5-6.3) were the strongest significant predictors of falls. In stratified multivariate analyses, preclinical disability equally predicted falls in participants with (OR = 1.7, 95% CI, 1.0-3.0) and without history of falls (OR = 1.8, 95% CI, 1.1-3.0). CONCLUSIONS: This study provides longitudinal evidence that self-reported preclinical disability predicts incident falls at 1-year follow-up independent of other self-reported fall risk factors. Multidimensional geriatric assessment that includes preclinical disability may provide a unique early warning system as well as potential targets for intervention.

R2-recanalization of spontaneous carotid artery dissection

BACKGROUND AND PURPOSE: We set out to investigate the predictors and time course for recanalization of spontaneous dissection of the cervical internal carotid artery (SICAD). METHODS: We prospectively included 249 consecutive patients (mean age, 45+/-11 years) with 268 SICAD. Ultrasound examinations were performed at presentation, during the first month, and then at 3, 6, and 12 months, and clinical follow-ups after 3, 6, and 12 months. RESULTS: Of 268 SICADs, 20 (7.5%) presented with <or=50% stenosis, 31 (11.6%) with 51% to 80% stenosis, 92 (34.3%) with 81% to 99% stenosis, and 125 (46.6%) with an occlusion. Antithrombotic treatment included anticoagulation in 174 (67%) patients, aspirin in 64 (24%) patients, and aspirin followed by anticoagulation or vice versa in 22 (8%) patients. Follow-up ultrasound showed normal findings in 160 (60%), <or=50% stenosis in 27 (10%), 51% to 80% stenosis in 4 (1%), 81% to 99% stenosis in 26 (10%), and occlusion in 51 (19%) vessels. The rate of complete recanalization was 16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Initial occlusion of the dissected vessels reduced the odds of recanalization (OR, 4.0; 95% CI, 2.2-7.3; P<0.001), whereas the occurrence of local symptoms and signs only at presentation were independently associated with complete recanalization (OR, 0.4; 95% CI, 0.2-0.8; P=0.048). CONCLUSIONS: These results suggest that recanalization of SICAD occurs mainly within the first 6 months after the onset of symptoms. Initial occlusion reduces the likelihood of complete recanalization, whereas presentation with local symptoms and signs only increases it.

Outcome of acute stroke patients without visible occlusion on early arteriography

BACKGROUND: The aim of this study was to determine the clinical and radiological outcome of acute stroke patients who had no vessel occlusion on arteriography and to define predictors of clinical outcome. METHODS: We analyzed clinical and radiological data of stroke patients whose arteriography performed within 6 hours of symptom onset did not visualize any vessel occlusion. RESULTS: Twenty-eight of 283 consecutive patients (10%) who underwent arteriography with the intention to perform intraarterial thrombolysis did not show any arterial occlusion. Their median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Time from symptom onset to arteriography ranged from 115 to 315 minutes; on average, it was 226 minutes. Presumed stroke cause was cardiac embolism in 11 patients (39%), small artery disease in 6 (21%), coronary angiography in 1 (4%), and undetermined in 10 patients (36%). After 3 months, modified Rankin Scale score (mRS) was < or =2 in 21 patients (75%), indicating a favorable outcome. Six patients (21%) had a poor outcome (mRS 3 or 4) and 1 patient (4%) had a myocardial infarction and died. Twenty-seven patients had follow-up brain imaging. It was normal in 5, showed a lacunar lesion in 8, a striatocapsular infarct in 2, a small or medium-sized anterior circulation infarct in 6, multiple small anterior circulation infarcts in 2, and multiple posterior circulation infarcts in 4. No predictors of clinical outcome were identified. CONCLUSIONS: Most acute stroke patients with normal early arteriography show infarcts on brain imaging; however, clinical outcome is usually favorable.

Quality of life in survivors after cervical artery dissection

BACKGROUND AND PURPOSE: Little data exists about longterm outcome, quality of life (QOL) and its predictors after spontaneous cervical artery dissections (sCAD). METHODS: Clinical and radiological data of 114 patients with sCAD were collected prospectively. Six patients died within 3 months, the remaining 108 were contacted after a mean of 1498 days (range: 379-3455), 99 survivors (92 %) replied. QOL, assessed with the stroke-specific QOL scale (SSQOL), and functional abilities, measured with modified Rankin Scale (mRS) were compared, and predictors of QOL were analyzed. Subgroup analyses were performed for patients with ischemic stroke, those with isolated local symptoms or transient ischemic symptoms and those without significant disabilities (mRS 0-1) at follow-up. RESULTS: Seventy-one of 99 patients (72 %) had no significant disability, but only 53 (54 %) reported a good QOL (SS-QOL > or = 4). Compared to the self-rated premorbid QOL of all patients, SS-QOL was impaired after sCAD (p < 0.001); impairment of QOL was observed in patients with ischemic stroke (p < 0.001), in patients with isolated local or transient ischemic symptoms (p < 0.038) and those without significant disabilities at follow-up (p = 0.013). Nevertheless, low mRS was associated with better overall QOL (Kendall's tau > 0.5). High National Institute of Health Stroke Scale score on admission and higher age were independent predictors of impaired QOL (p < 0.05). CONCLUSION: QOL is impaired in almost half of long-term survivors after sCAD, even in patients with local or transient symptoms or without functional disability. Impairment of QOL is a surprisingly frequent long-term sequela after sCAD and deserves attention as an outcome measure in these patients.