A systematic review of estimates of the minimal clinically important difference and patient acceptable symptom state of the Western Ontario and McMaster Universities Osteoarthritis Index in patients who underwent total hip and total knee replacement.

OBJECTIVE: To systematically review the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) estimates in pain and function measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in patients who underwent primary total knee replacement (TKR) and primary total hip replacement (THR). DESIGN: The study was carried out following PRISMA recommendations. We searched five electronic databases. Two reviewers independently screened titles, abstracts and full-text papers using a priori inclusion/exclusion criteria. Data were extracted by two independent reviewers. Data were synthesized, with WOMAC values converted to 0-100 scores (0 = best, 100 = worst). RESULTS: Thirteen studies were included. Research methods used to calculate MCIDs and PASS varied across studies (e.g., using anchor-based or distribution methods, wording of anchor questions within anchor-based methods). Baseline WOMAC scores also varied across studies. Across studies and methods, MCIDs for the WOMAC in patients undergoing TKR ranged from 13.3 to 36.0 for pain and 1.8-33.0 for function; values for WOMAC in THR ranged from 8.3 to 41.0 for pain and from 9.7 to 34.0 for function. PASS cut-offs for TKR ranged from 25.0 to 28.6 for pain and 32.3-36.7 for function, and cut-offs for THR from 15.0 to 30.6 for pain and 28.0-42.0 for function. CONCLUSION: Although the WOMAC is a commonly used measure for a single condition, the variability in methods used to calculate MCID and PASS estimates results in a range of values across studies making it unclear whether values reported in the literature can be applied with confidence. Future research is needed to refine methods used to calculate MCIDs and PASS.

High temporal variability in airborne bacterial diversity and abundance inside single-family residences.

Our homes are microbial habitats, and although the amounts and types of bacteria in indoor air have been shown to vary substantially across residences, temporal variability within homes has rarely been characterized. Here, we sought to quantify the temporal variability in the amounts and types of airborne bacteria in homes, and what factors drive this variability. We collected filter samples of indoor and outdoor air in 15 homes over 1 year (approximately eight time points per home, two per season), and we used culture-independent DNA sequencing approaches to characterize bacterial community composition. Significant differences in indoor air community composition were observed both between homes and within each home over time. Indoor and outdoor air community compositions were not significantly correlated, suggesting that indoor and outdoor air communities are decoupled. Indoor air communities from the same home were often just as different at adjacent time points as they were across larger temporal distances, and temporal variation correlated with changes in environmental conditions, including temperature and relative humidity. Although all homes had highly variable indoor air communities, homes with the most temporally variable communities had more stable, lower average microbial loads than homes with less variable communities.

The effect of irregular breathing patterns on internal target volumes in four-dimensional CT and cone-beam CT images in the context of stereotactic lung radiotherapy.

PURPOSE: Stereotactic lung radiotherapy is complicated by tumor motion from patient respiration. Four-dimensional CT (4DCT) imaging is a motion compensation method used in treatment planning to generate a maximum intensity projection (MIP) internal target volume (ITV). Image guided radiotherapy during treatment may involve acquiring a volumetric cone-beam CT (CBCT) image and visually aligning the tumor to the planning 4DCT MIP ITV contour. Moving targets imaged with CBCT can appear blurred and currently there are no studies reporting on the effect that irregular breathing patterns have on CBCT volumes and their alignment to 4DCT MIP ITV contours. The objective of this work was therefore to image a phantom moving with irregular breathing patterns to determine whether any configurations resulted in errors in volume contouring or alignment. METHODS: A Perspex thorax phantom was used to simulate a patient. Three wooden "lung" inserts with embedded Perspex "lesions" were moved up to 4 cm with computer-generated motion patterns, and up to 1 cm with patient-specific breathing patterns. The phantom was imaged on 4DCT and CBCT with the same acquisition settings used for stereotactic lung patients in the clinic and the volumes on all phantom images were contoured. This project assessed the volumes for qualitative and quantitative changes including volume, length of the volume, and errors in alignment between CBCT volumes and 4DCT MIP ITV contours. RESULTS: When motion was introduced 4DCT and CBCT volumes were reduced by up to 20% and 30% and shortened by up to 7 and 11 mm, respectively, indicating that volume was being under-represented at the extremes of motion. Banding artifacts were present in 4DCT MIP images, while CBCT volumes were largely reduced in contrast. When variable amplitudes from patient traces were used and CBCT ITVs were compared to 4DCT MIP ITVs there was a distinct trend in reduced ITV with increasing amplitude that was not seen when compared to true ITVs. Breathing patterns with a rest period following expiration resulted in well-defined superior edges and were better aligned using an edge-to-edge alignment technique. In most cases, sinusoidal motion patterns resulted in the closest agreements to true values and the smallest misalignments. CONCLUSIONS: Strategies are needed to compensate for volume losses at the extremes of motion for both 4DCT MIP and CBCT images for larger and varied amplitudes, and for patterns with rest periods following expiration. Lesions moving greater than 2 cm would warrant larger treatment margins added to the 4DCT MIP ITV to account for the volume being under-represented at the extremes of motion. Lesions moving with a rest period following expiration would be better aligned using an edge-to-edge alignment technique. Sinusoidal patterns represented the ideal clinical scenario, reinforcing the importance of investigating clinically relevant motions and their effects on 4DCT MIP and CBCT volumes. Since most patients do not breathe sinusoidally this may lead to misinterpretation of previous studies using only sinusoidal motion.

Disability management in a sample of Australian self-insured companies.

PURPOSE: Disability management (DM) is a term developed in North America and refers to the prevention and management of injury and illness in the workplace. The purpose of this paper is to report findings of an Australian study that examined whether self-insured employers in that country have implemented integrated DM programmes. Key principles underpinning such programmes are explored to identify the extent to which Australian employers have adopted them. METHOD: Data was collected from 29 self-insured Australian companies in three Australian States using a structured interview format with additional open-ended questions. RESULTS: It was found that companies have in place, to varying degrees, some of the key elements of disability management programmes. However, these elements were often not well integrated in a comprehensive disability management approach. The focus on workplace-based, early intervention in the area of return to work for injured employees was particularly strong, but there was little evidence of formal labour-management committee structures responsible for implementing DM programmes. CONCLUSIONS: If the concept of DM is relevant to the Australian environment then this study would suggest that self-insured companies need to undertake further work to develop integrated approaches to preventing and managing disability in the workplace. Several limitations of this study are highlighted and it is concluded that further work in this area is needed.

Mammography-related anxiety: effect of preprocedural patient education.

OBJECTIVES: To determine the effect of preprocedural education on mammography-related anxiety. MATERIALS AND METHODS: A total of 613 women undergoing mammography were surveyed regarding anxiety about the procedure and expected results. Half the study population watched an educational videotape and half watched an entertaining movie in the waiting room. RESULTS: Anxiety levels about results were significantly higher than anxiety levels about the procedure (P <.001). There was no difference in procedural or cancer anxiety levels among women shown the educational tape and those shown the entertaining movie. CONCLUSION: The fear of discovering breast cancer generates most of mammography-related anxiety. Preprocedural education did not affect procedural or cancer-related anxiety.

CT of the brain: a comparison of transportable and fixed-platform scanners.

OBJECTIVE: The purpose of this study was to determine whether an in-hospital transportable CT scanner can provide diagnostic brain images and to compare the quality of these images with those from a conventional fixed-platform CT scanner. SUBJECTS AND METHODS: Twenty-seven patients with known or suspected intracranial pathology underwent imaging on a transportable scanner and a fixed-platform scanner within 1 hr of each other. Images from each CT examination were evaluated independently by two neuroradiologists who were unaware of patient history. Conspicuousness of intracranial pathology and normal anatomy were rated on a 5-point scale (1 point, optimal; 5 points, poor or not visualized). Statistical comparisons were made using nonparametric tests. RESULTS: Seven CT scans were interpreted as showing normal findings and 20 scans revealed intracranial pathology on both CT scanners. Image quality was higher on the fixed scanner (average rating, 2.42 points; SE = .12) than on the transportable scanner (average rating, 3.10 points; SE = .12) (p = .001). Depiction of the cerebellum, midbrain, and supratentorial gray-white matter was better on the fixed scanner (p < .05). However, we found no significant differences in detection of intracranial pathology between scanners. Both radiologists found images from both scanners to be diagnostic in all 27 patients. CONCLUSION: Images of the brain on the transportable CT scanner were less clear than those on a fixed scanner. However, images from the transportable CT scanner were diagnostic in 27 consecutive patients. The implications of this finding are important for the provision of CT services for critically ill patients who cannot be transported to the radiology department.

Detecting hepatic lesions: the added utility of CT liver window settings.

PURPOSE: To prospectively evaluate the utility of adding computed tomographic (CT) liver windows to conventional soft-tissue windows for the detection of hepatic disease. MATERIALS AND METHODS: One of four radiologists experienced in abdominal imaging interpreted 1,175 consecutive abdominal CT scans from one institution. Hepatic images were first interpreted by using standard soft-tissue windows. The number of lesions and confidence in lesion detection were recorded. The liver-window images were then interpreted in conjunction with the soft-tissue-window images, and the number of lesions and confidence in detection were recorded again. The proportion of patients in whom additional lesions were found by using liver windows was determined. RESULTS: On soft-tissue-window and liver-window scans interpreted together, 869 (74%) patients had no hepatic lesions. Thirty-six (3.1%) patients had new lesions seen with the addition of liver windows. Twelve of these 36 patients had no lesions seen on soft-tissue-window scans. Twenty-six of the 36 patients with additional lesions seen had a history of neoplasm. There was a change in diagnosis in 1.7% of the patients with the addition of liver windows and a change in recommendation for follow-up in 0.85%. CONCLUSION: Routine interpretation of liver-window scans for all abdominal CT scans has limited added utility in detecting hepatic disease.

Experimental African HEV infection in cynomolgus macaques (Macaca fascicularis).

Experimental infection with hepatitis E virus (HEV) from Africa has not been investigated. Our purpose was to study hepatitis E produced by HEV from Chad (North Africa) and to analyze the genetic sequence of the HEV obtained after animal passage. An HEV-containing fecal sample from Chad was intravenously inoculated in four cynomolgus macaques. When serum Alanine Amino Transferase (ALT) levels rose, open liver biopsy and bile aspiration were performed. In all the monkeys, an ALT rise occurred 25 to 32 days after inoculation and new anti-HEV was detected by Enzyme Immuno Assay (EIA). Hepatic histopathology was consistent with acute viral hepatitis. HEV was detected by polymerase chain reaction (PCR) in bile (3/4 animals) and feces (2/4 animals) and by imunoelectron microscopy (IEM) in the inoculum and one bile specimen. A genetic variant HEV was identified in one monkey. The Chad HEV produced hepatitis E with pathophysiologic and histopathologic findings similar to those observed with HEV from other geographic origins. A genomic variant HEV population was produced after one passage in a macaque.

Characterization of hepatitis E virus (HEV) from Algeria and Chad by partial genome sequence.

The purpose of this study was to analyze partial nucleotide sequences and derived peptide sequences of hepatitis E virus (HEV) from two outbreaks of hepatitis E in Africa (Chad 1983-1984; Algeria 1978-1980). A portion of ORF3 and the major portion of ORF2 were amplified by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The PCR products were sequenced directly or after cloning into the pCRII vector. Sequences were then compared to the corresponding regions of reported full length HEV sequences. In the ORF2 and ORF3 regions, the homology between the Algerian and the Chad isolates at the nucleic acid level was 92 and 95%, respectively. At the peptide level the homology was 98% in both regions. In these regions, both strains are more related to Asian strains at the nucleic acid level (89 to 95%) and at the amino acid level (95 to 100%) than to the Mexico strain. At the peptide level the differences are less apparent. Both African isolates have amino acid changes in common with some reference strains although the Chad isolate has three unique changes. These African strains of HEV, based on the ORF2 and ORF3 phylogenetic trees, appear to be a distinct phylogenetic group, separate from the Mexican and Asian strains.

Exhaled ethane and antioxidant vitamin supplements in active smokers.

To determine the effect of nutritional agents on lipid peroxidation, 10 smokers were given 6 mg beta carotene, 200 IU vitamin E, and 250 mg vitamin C 4 times daily for 3 weeks. Lipid peroxidation was assessed by measuring baseline and postsupplementation levels of exhaled ethane. There was a 29% decrease in mean (+/-SD) exhaled ethane (4.06 +/- 1.49 vs 2.90 +/- 1.29 pmol.kg-1.min-1), with individual levels decreasing in 8 of the 10 smokers (p < 0.05, Wilcoxon sign rank test). Three nonsmokers had very low baseline levels of ethane that did not change with supplementation. Ethane production correlated with active (packs per day) and lifelong (pack-years) tobacco consumption. Also, a strong correlation was found between the decline in ethane output after micronutrient supplementation and the presupplement FEV1. Therefore, antioxidant vitamin supplementation resulted in attenuation of smoking-related lipid peroxidation, and the decreases in ethane production appears to be associated with preserved lung function.

Detection of K-ras gene mutations in non-neoplastic lung tissue and lung cancers.

Oncogene and tumor suppressor gene mutations are candidate biomarkers for cancer risk assessment and lesion detection. The K-ras oncogene has previously been associated with non-small cell lung cancer (NSCLC), particularly adenocarcinomas in which reported rates of mutation have approached 30-40%. We have analyzed non-malignant lung tissue from patients with lung cancer and primary lung cancers for K-ras gene mutations. Mutations were detected in 32% cancers and 29% non-malignant lung tissue from patients with cancer. The majority of tumors testing positive were adenocarcinoma of the lung. Normal DNA controls, including peripheral blood lymphocytes and normal lung from non-smokers, were negative. The ability to detect genetic alterations in non-malignant lung tissues is consistent with the concept that genetic alterations are involved in field cancerization of the aerodigestive tract.

Analysis of K-ras gene mutations in malignant and nonmalignant endobronchial tissue obtained by fiberoptic bronchoscopy.

Using polymerase chain reaction DNA amplification, we identified K-ras oncogene mutations in bronchial biopsies obtained from patients undergoing bronchoscopy for clinical indications. We hypothesized that these mutations would be found in a field encompassing malignant and nonmalignant tissues in patients with pulmonary carcinomas, and also possibly in tissue from some patients who smoked but did not have pulmonary malignancy. We found K-ras mutations in endobronchial biopsies from nine of 22 patients (41%) with carcinoma of the lung. In five of these patients, mutations were found in both malignant and nonmalignant specimens. In two instances, mutations were found only in the neoplastic tissue, and in two cases mutations were present only in the nonmalignant tissue. Furthermore, we identified two patients with K-ras mutations among seven patients in whom no clinical malignancy was apparent. Our data suggest that some oncogene activations may occur over a broad area in smokers with and without malignancy, and they imply that K-ras mutations may serve as surrogate markers for malignant potential.

Cigarette smoking and ethane exhalation in humans.

The time course of exhaled ethane gas was determined in the alveolar expirate of healthy, fasting smokers and nonsmokers after smoking a cigarette. Baseline ethane was measured by gas chromatography and corrected for background ethane after a 2-min washout using purified air. Ethane was measured immediately after smoking and hourly thereafter. Ethane was highest immediately after smoking, reflecting ethane in cigarette smoke. An exponential decline of ethane in smokers returned ethane to baseline within 3 h. Ethane in nonsmokers also peaked immediately after smoking but returned to baseline by 1 h. Ethane from smokers, measured 3 h after the last cigarette, was compared with ethane from healthy ex-smokers and nonsmokers. Mean (+/- SEM) baseline ethane in smokers was 2.90 +/- 0.52 pmol/min/kg, 1.55 +/- 0.36 pmol/min/kg in ex-smokers and 1.11 +/- 0.26 pmol/min/kg in nonsmokers (p < 0.05). Ethane in two smokers measured before and after a week of oral beta carotene supplementation (60 mg/d) fell by 80 and 35%. We conclude that cigarette smokers have increased baseline ethane in exhaled breath compared with non-smokers. Trials with antioxidant agents are warranted to assess their ability to reduce expired ethane levels.

The early pattern of conjugated dienes in liver and lung after endotoxin exposure.

If lipid peroxidation (LP) contributes to organ dysfunction in sepsis rather than simply reflecting established injury, it should occur soon after the onset of the septic insult, and it may not progress uniformly in all organs. We assessed whether LP occurs within 90 min after onset of continuous intravenous endotoxin (E. coli 055:B5) infusion in rats, using second-derivative spectroscopy to semiquantitatively assess conjugated dienes (CD) in lung, liver, and plasma phospholipids. Measurements were also made after 90-min infusions with saline or 1 mM H2O2. Both the quantity and spectrophotometric patterns of CD differed between the three groups. Compared with saline controls, lung lipid CD increased after both H2O2 and endotoxin. Venous plasma CD were elevated only after H2O2, while arterial plasma and liver lipid CD were not different between the three groups. Exhaled ethane (an indicator of peroxidation of omega-3 fatty acids) did not differ between groups. Wet-to-dry lung weights were significantly increased after endotoxin compared with that after saline controls. Our results indicate that tissue-specific LP occurs within 90 min of endotoxin or H2O2 intravenous infusion.

Effects of low-dose hydrogen peroxide in the isolated perfused rat lung.

Isolated perfused rat lungs (IPRL) were used to determine if treatment with hydrogen peroxide would result in measurable changes in exhaled ethane during the early stages of capillary leak. Pulmonary capillary filtration coefficient, pulmonary vascular resistance, and dynamic pulmonary compliance were measured at two time points in an IPRL. Additionally, exhaled ethane was determined before and after the addition of 0.25 mM H2O2 to the perfusate in a second group of lungs. Lung wet/dry weight ratios were measured at the termination of the experiments. The ethane in the exhaled alveolar gas from IPRLs ventilated with 5%CO2/20%O2/balance N2 was quantitated using gas chromatography before and after the addition of 0.25 mM H2O2 to Krebs Ringer's 5% albumin perfusate. H2O2 (0.25 mM) caused a small but significant increase in capillary filtration coefficient from 0.0122 (+/- 0.0008) to 0.0173 (+/- 0.0013) mL/min/cm H2O/g dry lung weight (p < .05). Wet/dry lung weight ratios were increased in the H2O2-treated lungs (6.0654 +/- 0.1024 versus 5.4149 +/- 0.1143; p < .05). Exhaled ethane did not increase over the period of time hydrogen peroxide was present in the perfusate. In other experiments in closed-chested rats, 0.25 mM peroxide did not cause increased exhaled ethane, whereas 1 mM H2O2 did. This latter increase in ethane was not noted in similarly perfused open-chested rats. These data indicate that small amounts of H2O2 may increase pulmonary capillary permeability without affecting exhaled ethane measurements.

Heterotopic ossification complicating critical illness.

Heterotopic ossification (HO), deposition of para-articular ectopic bone, is associated with musculoskeletal trauma and certain congenital and metabolic disorders. Additionally, HO may follow paralysis from diverse traumatic and nontraumatic neurologic insults. We describe three cases of HO associated with catastrophic nontraumatic respiratory illness requiring prolonged chemical paralysis and cardiorespiratory support.

Idiopathic hemothorax.

Development of spontaneous hemothorax without predisposing conditions is extremely rare. We report a young man with a history of a seizure disorder who presented to the emergency department with spontaneous hemothorax. Exploratory thoracotomy evacuated 2,000 ml of old blood. No source of hemorrhage was identified. To our knowledge, this is the first report of spontaneous hemothorax proved by thoracotomy.

Lack of an association between the presence of tumor necrosis factor or interleukin-1 alpha in the blood and weight loss among elderly patients.

To determine the association between blood cytokine levels and body weight loss in elderly patients, serum levels of cachectin/tumor necrosis factor alpha (TNF) and interleukin-1 alpha (IL-1) were measured with specific and sensitive ELISA systems. Of the 19 healthy young subjects, two (10.5%) had detectable levels of serum TNF and one (5.3%) was positive for IL-1. In the healthy elderly group, two of the 12 subjects (16.7%) had measurable TNF levels and four (33.3%) had elevated IL-1 levels. Of the 61 ambulatory elderly patients, 31.1% had serum that contained TNF and 22.9% had IL-1. Similar proportions were found in 127 nursing home patients. None of the common diseases examined in this study nor any commonly used medications were associated with increased serum cytokine levels. Patients with weight loss of more than 5 lbs were less likely to have elevated serum TNF and IL-1 levels compared to the rest of the group. It is concluded that although elevated levels of TNF or IL-1 may occur more frequently in older groups, there is no evidence for a causal relationship between these circulating cytokines and clinically significant weight loss in the elderly.

Use of high-performance liquid chromatography in the evaluation of the synthesis and binding of fluorescein linked steroids to estrogen receptors.

A fluorescein-linked estrogen was synthesized as a non-invasive, non-radiochemical means of detecting the levels and distribution of estrogen receptors in histological preparations of breast and endometrium. 17 alpha-Ethynylestradiol-21-carboxylic acid was coupled via octane-1,8-diamine to fluorescein-isothiocyanate yielding a promising ligand, N-fluoresceinyl-5,N"-[8-(3,17 beta-dihydroxy-19-nor-17 alpha-pregna-1,3,5 (10)-triene-20-yne-21-carboxylic acid amide)]octylthiourea (F8DE) for an estrogen receptor. High-performance liquid chromatography on preparative reversed-phase C18 columns was used to purify the final product. Using cytosolic receptor preparations from bovine uterus and human uterus and breast cancer, the binding of F8DE was determined by competition analyses to have a Kd value of 10(-8) M. High- and low-molecular-weight forms of estrogen receptors were separated on TSK 3000SW and 4000SW columns by high-performance size-exclusion chromatography. Specific binding of radio labeled estradiol-17 beta to these forms was inhibited in the presence of F8DE, indicating association with the fluorescein-linked steroid.